Carvykti (ciltacabtagene autoleucel) is a personalized CAR T-cell therapy used to treat relapsed or refractory multiple myeloma (RRMM). It is used in adults whose multiple myeloma has returned or stopped responding to earlier treatments and may be used as early as the first relapse in certain patients.

Carvykti is a one-time infusion using a patient’s own genetically modified T cells to recognize and destroy multiple myeloma cells that express the BCMA protein.

For Carvykti treatment, T cells (a type of white blood cell) are collected from your blood and modified at the manufacturing site. A specialized receptor, called a chimeric antigen receptor (CAR), is added to the surface of the T cells. This enables it to recognize and attack multiple myeloma cells that carry the BCMA protein.

Once modified, the T cells are multiplied and infused back into your body as a personalized immunotherapy. After infusion, these CAR-T cells can seek out and kill BCMA-expressing multiple myeloma cells, helping improve disease control and clinical outcomes.

Carvykti is a BCMA-targeted CAR-T cell therapy.

Who Is Eligible for Carvykti Therapy?

Carvykti is FDA approved for the treatment of adults with relapsed or refractory multiple myeloma who meet all of the following criteria:

• Have multiple myeloma that has returned or stopped responding to treatment
• Have received at least one prior line of therapy
• Have been treated with:
  • A proteasome inhibitor, and
  • An immunomodulatory agent
• Have disease that is refractory to lenalidomide (no longer responds to lenalidomide treatment)

Carvykti may be used as early as the first relapse in appropriate patients when previous therapies have not been effective.

What is the Carvykti treatment process?

The Carvykti CAR T-cell therapy process is:

• T-cell collection: T cells, a type of white blood cell, are collected from your blood through a process called leukapheresis.
• Genetic modification: At a specialized manufacturing facility, a chimeric antigen receptor (CAR) is added to the surface of the T cells.
• Targeting BCMA: This CAR enables the T cells to recognize BCMA (B-cell maturation antigen), a protein found on multiple myeloma cells.
• Cell expansion: The modified CAR T cells are multiplied in the laboratory to create a sufficient number of cells for treatment.
• One-time infusion: The modified T cells are infused back into your body as a personalized immunotherapy.
• Cancer cell attack: After infusion, the CAR-T cells seek out and kill BCMA-expressing multiple myeloma cells, helping improve disease control and clinical outcomes.

How effective is Carvykti for RRMM?

New data from the Phase 3 CARTITUDE-4 study (NCT04181827) demonstrated that Carvykti was more effective than standard therapy.

• At 12 months, the estimated progression-free survival (PFS) rate was 75.9% with Carvykti compared to 49.5% with standard therapy. 
• In addition, 74.0% of patients treated with Carvykti achieved a complete response or better, while only 22.3% of patients on standard therapy reached that level of response. 
• An update to this study at a median follow-up of 33.6 months reported a statistically significant improvement in the overall survival rate with Carvykti compared to standard therapy.

These response rates were assessed by an Independent Review Committee (IRC) using the International Myeloma Working Group (IMWG) criteria.

Boxed Warnings

Carvykti has boxed warnings for cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), Parkinsonism and Guillain-Barré syndrome (GBS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), prolonged and/or recurrent cytopenias, immune-effector cell-associated enterocolitis (IEC-EC), and secondary hematological malignancies. 

A boxed warning is the strongest safety-related warning issued by the FDA. 

• Cytokine Release Syndrome (CRS). This includes fatal or life-threatening reactions, that have occurred in patients following treatment with Carvykti. Do not administer this medicine to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). This may be fatal or life-threatening, and has occurred following treatment with Carvykti, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with Carvykti .  Supportive care and/or corticosteroids should be provided as needed.
• Parkinsonism and Guillain-Barré syndrome and their associated complications have occurred following Carvykti treatment resulting in fatal or life-threatening reactions.
• Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, have occurred in patients following treatment with this medicine. HLH/MAS can occur with CRS or neurologic toxicities.
• Prolonged or recurrent cytopenias (low blood cell counts) have occurred after treatment with Carvykti and may be associated with bleeding, infection, and the need for stem cell transplantation to restore blood cell production.
• Immune Effector Cell–associated enterocolitis (IEC-EC), including fatal or life-threatening reactions, has been reported following treatment with Carvykti.
• Secondary blood cancers, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), have occurred after treatment with Carvykti. T-cell malignancies have also been reported following treatment of blood cancers with BCMA- and CD19-directed genetically modified autologous T-cell therapies, including Carvykti. 

Warnings and Precautions

• Prolonged and Recurrent Cytopenias: Cytopenia is low levels of red blood cells (anemia), white blood cells (leukopenia) or platelets (thrombocytopenia). Cytopenia may occur after Carvykti infusion. Prolonged neutropenia has been associated with increased risk of infection. Blood counts should be monitored before and after the infusion.
• Infections: Patients should be monitored for signs and symptoms of infection and receive appropriate treament if necessary.
• Hypogammaglobulinemia (low levels of immunoglobulins):  Your immunoglobulin levels will be monitored and immunoglobulin replacement therapy may be considered if required.
• Hypersensitivity Reactions: Hypersensitivity reactions have occurred. Monitor for hypersensitivity reactions during infusion. ( 5.8)
• Secondary Malignancies: Secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, have occurred. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including this medicine. Contact Janssen Biotech, Inc. at 1-800-526-7736, if this occurs.
• Immune-effector cell-associated enterocolitis (IEC-EC): Carvykti can cause serious gastrointestinal side effects, including severe or persistent diarrhea or ruptured bowel, which can be life-threatening and may lead to death. Tell your healthcare provider right away if you develop diarrhea, abdominal pain, weight loss, fever, chills, or any signs or symptoms of an infection. 

Differences in survival rates in the first 10 months were found in a study comparing Carvykti to standard therapy.

• 14% in the Carvykti arm died compared to 12% in the standard therapy arm.
• The increased death rate occurred before and after receiving Carvykti treatment.
• The reasons for death were progression of multiple myeloma and side effects of the treatment. 

However, the FDA has determined that the overall benefit of Carvykti continues to outweigh the potential risks. 

Carvykti side effects

Carvykti common side effects

Carvykti Common side effects may include:

• confusion, cough, trouble breathing, fast or irregular heartbeats, feeling light-headed or very tired;
• headache, dizziness;
• problems with speech;
• low blood cell counts;
• fever, chills, tiredness, or other signs of infection;
• decreased appetite, constipation, nausea, or diarrhea; or
• pain in your joints or muscles.

Serious side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

A serious side effect of Carvykti is called cytokine release syndrome (CRS). Tell your caregivers right away if you have signs of this condition: fever, chills, trouble breathing, severe vomiting or diarrhea, tremors, shaking, fast or irregular heartbeats, feeling light-headed, or feeling very tired. Your caregivers will have medication available to quickly treat CRS if it occurs.

Also, call your doctor at once if you have:

• confusion, loss of consciousness, seizures, problems with speech, reading, or writing, depression
• personality changes, including a reduced ability to express emotions, being less talkative,
  disinterest in activities, and reduced facial expression
• tingling and numbness of hands and feet, leg and arm weakness, facial numbness; or
• low blood cell counts – fever, chills, tiredness, flu-like symptoms, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath
• persistent or severe diarrhea, abdominal pain, and weight loss.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects.

Before taking this medicine

Tell your doctor if you have ever had:

• neurologic problems (such as stroke, seizures, memory loss);
• breathing problems;
• heart problems;
• liver or kidney disease;
• diarrhea;
• recent or active infection; or
• low blood counts.

Pregnancy

Carvykti is not recommended for women who are pregnant or for women of childbearing potential not using contraception. Pregnant women should be advised that there may be risks to the fetus. Pregnancy after this therapy should be discussed with the treating physician.

Women will need pregnancy testing before receiving this medicine. You will also need to use birth control to prevent pregnancy during treatment with this medicine. Tell your doctor if you are pregnant or plan to become pregnant.

Breastfeeding

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risks.

How should I receive Carvykti?

The Carvykti treatment process involves:

1. T-cell collection – A patient’s white blood cells (T cells) are collected via leukapheresis.
2. Genetic modification – The T cells are engineered to express a CAR that recognizes BCMA, a protein highly expressed on multiple myeloma cells.
3. Expansion and conditioning – The modified T cells are multiplied in a lab, while the patient undergoes lymphodepleting chemotherapy to prepare for infusion.
4. One-time infusion – The patient receives an intravenous (IV) infusion of Carvykti.
5. Post-treatment monitoring – Patients are closely monitored for cytokine release syndrome (CRS) and other potential side effects.

Dosing information

Recommended dose: 0.5-1.0×10⁶ CAR-positive viable T cells per kg, with a maximum dose of 1×10⁸ CAR-positive viable T cells per infusion.

Pre-medication required: Acetaminophen and an H1-antihistamine before infusion.

General dosing information:

• Administered intravenously at an authorized facility.
• Patients should stay within 2 hours of the treatment facility for at least 4 weeks post-infusion for monitoring.

What should I avoid after receiving this medicine?

• Do not drive, operate heavy machinery, or do other activities that could be dangerous if you are not mentally alert for at least 8 weeks after you get Carvykti. This is because the treatment can cause memory and coordination problems, sleepiness, confusion, dizziness, seizures, or other neurologic side effects, as discussed by your healthcare provider.
• You must not be given certain vaccines called live vaccines for some time before and after Carvykti treatment. Talk to your healthcare provider if you need to have any vaccinations.
• Do not donate blood, organs, tissues, or cells for transplantation.

What other drugs will affect Carvykti?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Some commercial Human Immunodeficiency Virus (HIV) tests may incorrectly give you an HIV-positive result while you are receiving treatment with Carvykti.

Carvykti Package Insert

HCPs and patients often use the Carvykti Package Insert (PI) for more detailed information about this medicine. The Carvykti Package Insert contains more detailed information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interaction, and more. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

The Package Insert is sometimes called the FDA label, or Carvykti Prescribing Information (PI).

Ingredients

Active ingredient: ciltacabtagene autoleucel

Inactive ingredients: DMSO

Manufacturer Information

Carvykti Manufacturer Janssen Biotech, Inc., Horsham, PA, USA.

Marketing Partner Legend Biotech, Somerset, NJ, USA.

Carvykti Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Carvykti.Carvykti (ciltacabtagene autoleucel) – Janssen Biotech, Inc.

Breyanzi is used to treat 5 types of non-Hodgkin lymphoma, including large B-cell lymphoma (LBCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), follicular lymphoma (FL), and relapsed or refractory mantle cell lymphoma (MCL), with relapsed or refractory (R/R) marginal zone lymphoma (MZL) in specific patients.

Breyanzi is a one-time infusion of CAR T cell therapy that may help you have complete and lasting remission. 

Breyanzi is a cancer treatment created using immune cells, called T cells, collected from the patient’s own blood. The T cells are modified to become CAR T cells and are then infused back into the patient’s body. The CART T cells can attach to the cancer cells and kill them, helping clear the cancer from the body.  Before your infusion, you will have chemotherapy to prepare your body for your treatment. 

Breyanzi FDA approval was first received on February 5, 2021, for the company Bristol Myers Squibb (BMS).  It contains lisocabtagene maraleuce. The most recent approval was for relapsed or refractory marginal zone lymphoma (MZL) on December 4, 2025.

What is Breyanzi used for?

Breyanzi is FDA-approved to treat five types of non-Hodgkin lymphoma: large B-cell lymphoma, relapsed or refractory chronic CLL/SLL, relapsed or refractory follicular lymphoma (FL), and relapsed or refractory mantle cell lymphoma (MCL), and relapsed or refractory (R/R) marginal zone lymphoma (MZL)  in specific patients.

Large B-cell lymphoma

Breyanzi is used to treat large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, in adults. You can only be treated with Breyanzi if:

• your first treatment has not worked, or your cancer returned within a year of your first treatment, OR
• your first treatment has not worked, or your cancer returned after the first treatment, and you are not eligible for hematopoietic stem cell transplantation because of medical conditions or age, OR
• two or more kinds of treatment have not worked or stopped working.

It is not indicated for the treatment of primary central nervous system lymphoma.

Relapsed or refractory chronic CLL/SLL

Breyanzi is used to treat relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adults who have:

• received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. 
• This is an accelerated FDA approval.

Relapsed or refractory follicular lymphoma (FL) 

Breyanzi is used to treat relapsed or refractory follicular lymphoma (FL) in adults who have:

• received 2 or more prior lines of systemic therapy. 
• This is an accelerated FDA approval.

Relapsed or Refractory Mantle Cell Lymphoma (MCL)

It is approved for treating adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor.

Relapsed or refractory (R/R) marginal zone lymphoma (MZL)

Breyanzi is approved for adult patients who have received at least two prior lines of systemic therapy.

Breyanzi side effects

Common Breyanzi side effects

Common Breyanzi side effects may include:

• headache, dizziness;
• confusion, problems with speech or thinking;
• fever, chills, shaking;
• nausea, vomiting, stomach pain;
• diarrhea, constipation;
• fast or irregular heartbeats;
• cough, trouble breathing;
• swelling; or
• pain in your bones, joint, or muscles.

Serious Bryanzi side effects

Get emergency medical help if you have signs of an allergic reaction, hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.

A common but serious side effect of this medicine is called cytokine release syndrome (CRS). Tell your caregivers right away if you have signs of this condition: fever, chills, dizziness, confusion, vomiting, diarrhea, fast heartbeats, trouble breathing, or feeling very weak or tired. Your caregivers will have medication available to treat CRS if it occurs.

Breyanzi may cause other serious side effects. Call your doctor at once if you have:

• problems with speech;
• confusion, trouble concentrating, memory problems;
• decreased consciousness;
• tremors, or a seizure; or
• signs of infection – fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath.

Breyanzi may increase your risk of developing certain cancers. Talk to your doctor about the risks of receiving this medication. This medication may cause other side effects. Call your doctor if you have any unusual problems while receiving this medication. If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online .

How will I receive Breyanzi?

Breyanzi is a one-time cancer treatment made from your own white blood cells. The process takes several weeks and involves collecting, modifying, and then infusing those cells back into your body, with close monitoring for side effects.

Breyanzi is a liquid medicine given intravenously (into a vein) by a doctor or nurse. It is usually given as two infusions over about 30 minutes total as a one-time dose.

Breyanzi treatment process

Step 1: T Cell collection

• T cells, which are a type of white blood cell, are collected using a procedure called leukapheresis (a process that removes white blood cells from the body).

Step 2: T Cell activation

• The collected T cells are sent away and modified so they can better recognize and attack cancer cells.
• This modification process takes about 3–4 weeks.

Step 3: Preparation for infusion

• You will receive chemotherapy medicines a few days before Breyanzi to prepare your body; this is called lymphodepleting chemotherapy.

Step 4: Breyanzi infusion

• The modified cells are then infused back into your body as Breyanzi. Because the treatment is made from your own cells, it must only be given to you.

Step 5: Follow-up

• Your healthcare provider will check if the treatment is working and monitor for side effects.
  You should plan to stay near the treatment center for at least 4 weeks after receiving Breyanzi.

It is very important not to miss your cell collection or treatment appointment

Before taking this medicine

Tell your doctor if you have ever had:

• hepatitis B or C; or
• if you have received a vaccine within the past 6 weeks.

Using Breyanzi may increase your risk of developing other cancers. Ask your doctor about this risk.

Tell your doctor if you are pregnant or breastfeeding.

You may need to have a negative pregnancy test before starting this treatment.

Warnings

Breyanzi has a boxed warning for cytokine release syndrome(CRS), neurologic toxicity, and secondary hematological malignancies.

Cytokine release syndrome (CRS): This is a common but serious side effect of this medicine is called cytokine release syndrome, which causes fever, chills, trouble breathing, vomiting, and other symptoms. Your caregivers will have medication available to treat this condition if it occurs.

Breyanzi may cause severe or life-threatening central nervous system reactions. These reactions can occur after treatment with this medicine. Tell your doctor if you have or have ever had seizures, a stroke, or memory loss. If you experience any of the following symptoms, tell your doctor immediately: headache, dizziness, difficulty falling asleep or staying asleep, restlessness, confusion, anxiety, uncontrollable shaking of a part of the body, loss of consciousness, agitation, seizures, loss of balance, or difficulty speaking.

T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including this therapy.

What should I avoid after receiving Breyanzi?

 Avoid driving or operating machinery for at least 2 weeks after receiving this treatment. This medicine can cause weakness, drowsiness, confusion, problems with memory or coordination, and seizures.

Do not donate blood, organs, tissues, or cells for transplantation.

Do not have any vaccinations without talking to your doctor for at least 6 weeks before starting chemotherapy, during your Breyanzi treatment, and until your doctor tells you your immune system has recovered

What other drugs will affect Breyanzi?

Other drugs may affect this medicine, including prescription and over-the-counter medicines, vitamins, and herbal products. You should keep a written list of all the prescription and nonprescription (over-the-counter) medicines you take, along with any products such as vitamins, minerals, or other dietary supplements. Remember to bring this list with you each time you see a doctor or are hospitalized. This information is important to have on hand for emergencies.

What is Idhifa?

Idhifa targets a specific gene mutation called IDH2, which can affect your bone marrow. IDH2 mutation prevents young blood cells from developing into healthy adult blood cells, which can result in symptoms of acute myeloid leukemia.

Idhifa is used to treat acute myeloid leukemia in adults with an IDH2 mutation.

Idhifa is used when AML has come back or has not improved with prior treatment.

Warnings

Idhifa can cause a condition called differentiation syndrome, which affects blood cells and can be fatal if not treated. This condition may occur within 10 days to 5 months after you start taking this medicine.

Seek medical help right away if you have symptoms of differentiation syndrome: fever, cough, trouble breathing, bone pain, rapid weight gain, or swelling in your arms, legs, underarms, groin, or neck.

Before taking this medicine

You should not use Idhifa if you are allergic to enasidenib.

Before using Idhifa tell your doctor about all your medical conditions or allergies.

You may need to have a negative pregnancy test before starting this treatment. In animal studies, enasidenib caused miscarriage, low birth weight, stillbirth, and birth defects.

Enasidenib may harm an unborn baby. Use a barrier form of birth control (condom or diaphragm with spermicide) to prevent pregnancy while you are using Idhifa. Hormonal contraception (birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective enough to prevent pregnancy during your treatment.

You should use birth control to prevent pregnancy while using this medicine whether you are a man or a woman. Idhifa use by either parent may cause birth defects.

Keep using birth control for at least 2 months after your last dose of Idhifa. Tell your doctor right away if a pregnancy occurs while either the mother or the father is using enasidenib.

Idhifa may affect fertility (ability to have children) in both men and women. However, it is important to use birth control to prevent pregnancy because enasidenib may harm the baby if a pregnancy does occur.

It is not known whether enasidenib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine, and for at least 1 month after your last dose.

How should I take Idhifa?

Take Idhifa exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Take Idhifa exactly as prescribed by your doctor. Idhifa is usually given once per day. Take this medicine with a full glass of water, at the same time each day. Drink plenty of liquids while you are taking this medicine.

You may take this medicine with or without food.

Do not crush, chew, or break a tablet. Swallow the tablet whole.

Idhifa is usually given until your body no longer responds to the medication.

If you vomit shortly after taking Idhifa, do not take another dose. Take your next dose as scheduled.

You may need frequent medical tests to be sure this medicine is not causing harmful effects. Your cancer treatments may be delayed based on the results of these tests.

Store at room temperature away from moisture and heat. Keep the tablets in their original container, along with the canister of moisture-absorbing preservative.

Dosing information

Usual Adult Dose for Acute Myeloid Leukemia:

100 mg orally once a day with or without food

Duration of Therapy:
-Treat until disease progression or unacceptable toxicity.
-For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response.

Comments: Select patients based on the presence of isocitrate dehydrogenase-2 (IDH2) mutations in the blood or bone marrow as detected by an FDA-approved test, http://www.fda.gov/CompanionDiagnostics.

Use: Treatment of relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation.

What happens if I miss a dose?

Take the missed dose on the same day you remember it. Take your next dose at the regular time and stay on your once-daily schedule. Do not use 2 doses in one day.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What to avoid

Follow your doctor’s instructions about any restrictions on food, beverages, or activity.

Idhifa side effects

Get emergency medical help if you have signs of an allergic reaction to Idhifa: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Idhifa can cause a condition called differentiation syndrome, which affects blood cells and can be fatal if not treated. This condition may occur within 10 days to 5 months after you start taking Idhifa.

Seek medical help right away if you have symptoms of differentiation syndrome:

• fever, cough, trouble breathing;
• bone pain;
• rapid weight gain; or
• swelling in your arms, legs, underarms, groin, or neck.

Call your doctor at once if you have any of these side effects:

• dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
• severe or ongoing vomiting or diarrhea; or
• signs of tumor cell breakdown – tiredness, weakness, muscle cramps, nausea, vomiting, diarrhea, fast or slow heart rate, decreased urination, tingling in your hands and feet or around your mouth.

Common Idhifa side effects may include:

• nausea, vomiting, diarrhea;
• loss of appetite; or
• jaundice.

What is isotretinoin?

Isotretinoin is a form of vitamin A that is used to treat severe nodular acne that has not responded to other treatments, including antibiotics.

Isotretinoin is available only from a certified pharmacy under a special program called iPLEDGE.

Isotretinoin may also be used for purposes not listed in this medication guide.

Isotretinoin side effects

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Isotretinoin may cause serious side effects. Stop using isotretinoin and call your doctor at once if you have:

• problems with your vision or hearing;
• muscle or joint pain, bone pain, back pain;
• increased thirst, increased urination;
• hallucinations, (see or hearing things that are not real);
• symptoms of depression–unusual mood changes, crying spells, feelings of low self-worth, loss of interest in things you once enjoyed, new sleep problems, thoughts about hurting yourself;
• signs of liver or pancreas problems–loss of appetite, upper stomach pain (that may spread to your back), nausea or vomiting, fast heart rate, dark urine, jaundice (yellowing of the skin or eyes);
• severe stomach problems–severe stomach or chest pain, pain when swallowing, heartburn, diarrhea, rectal bleeding, bloody or tarry stools; or
• increased pressure inside the skull–severe headaches, ringing in your ears, dizziness, nausea, vision problems, pain behind your eyes.

Common side effects of isotretinoin may include:

• dryness of your skin, lips, eyes, or nose (you may have nosebleeds);
• vision problems;
• headache, back pain, joint pain, muscle problems;
• skin reactions; or
• cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA .

Warnings

Isotretinoin in just a single dose can cause severe birth defects or death of a baby. Never use isotretinoin if you are pregnant or able to become pregnant.

You must have a negative pregnancy test before taking isotretinoin. You will also be required to use two forms of birth control to prevent pregnancy while taking this medicine. Stop using isotretinoin and call your doctor at once if you think you might be pregnant.

Before taking this medicine

Isotretinoin can cause miscarriage, premature birth, severe birth defects, or death of a baby if the mother takes this medicine at the time of conception or during pregnancy. Even one dose of isotretinoin can cause major birth defects of the baby’s ears, eyes, face, skull, heart, and brain. Never use isotretinoin if you are pregnant or able to become pregnant.

For Women: Unless you have had your uterus and ovaries removed (total hysterectomy with oophorectomy) or have been in menopause for at least 12 months in a row, you are considered to be able to get pregnant. You must have 2 negative pregnancy tests before you start taking isotretinoin, before each prescription is refilled, right after you take your last dose of isotretinoin, and again 30 days later. All pregnancy testing is required by the iPLEDGE program.

You must agree in writing to use two specific forms of birth control beginning 30 days before you start taking isotretinoin and ending 30 days after your last dose. Both a primary and a secondary form of birth control must be used together.

Primary forms of birth control include:

• tubal ligation (tubes tied);
• vasectomy of the male sexual partner;
• an IUD (intrauterine device);
• estrogen-containing birth control pills (not mini-pills); and
• hormonal birth control patches, implants, injections, or vaginal ring.

Secondary forms of birth control include:

• a male latex condom with or without spermicide;
• a diaphragm plus a spermicide;
• a cervical cap plus a spermicide; and
• a vaginal sponge containing a spermicide.

Stop using isotretinoin and call your doctor at once if you have unprotected sex, if you quit using birth control, if your period is late, or if you think you might be pregnant. If you get pregnant while taking isotretinoin, call the iPLEDGE pregnancy registry at 1-866-495-0654.

Not having sexual intercourse (abstinence) is the most effective method of preventing pregnancy.

You should not use isotretinoin if you are allergic to it.

Tell your doctor if you have ever had:

• depression or mental illness;
• asthma;
• liver disease;
• diabetes;
• heart disease or high cholesterol;
• osteoporosis or low bone mineral density;
• an eating disorder such as anorexia;
• a food or drug allergy; or
• an intestinal disorder such as inflammatory bowel disease or ulcerative colitis.

Do not breastfeed.

Not approved for use by anyone younger than 12 years old.

How should I take isotretinoin?

Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

Each prescription of isotretinoin must be filled within 7 days of the date it was written by your doctor. You will receive no more than a 30-day supply of isotretinoin at one time.

Always take isotretinoin with a full glass of water. Do not chew or suck on the capsule. Swallow it whole.

Follow all directions about taking isotretinoin with or without food.

Use isotretinoin for the full prescribed length of time. Your acne may seem to get worse at first, but should then begin to improve.

You may need frequent blood tests.

Never share this medicine with another person, even if they have the same symptoms you have.

Store at room temperature away from moisture, heat, and light.

Isotretinoin dosing information

Usual Adult Dose for Acne:

Maintenance dose: 0.25 to 0.5 mg/kg orally 2 times a day
Maximum dose: Up to 2 mg/kg/day
Duration of therapy: Up to 20 weeks

Comments:
-Patients should take some formulations of this drug with food.
-Prior to increasing the dose, patients should be asked about their compliance with treatment (e.g., taking this drug with food).
-Patients with very severe acne, scarring, or primary manifestations on the trunk may require 2 mg/kg/day dosing.
-Any patient requesting refills requires a new prescription and a new authorization from the iPLEDGE program.
-The safety and efficacy of once a day dosing has not been established; thus, once a day dosing is not recommended.

Use: Treatment of severe recalcitrant nodular acne in patients who are unresponsive to conventional therapy, including systemic antibiotics

Usual Pediatric Dose for Acne:

12 years or older:
-Maintenance dose: 0.25 to 0.5 mg/kg orally 2 times a day
-Maximum dose: 2 mg/kg/day
-Duration of therapy: Up to 20 weeks

Comments:
-Patients should take some formulations of this drug with food.
-Prior to increasing the dose, patients should be asked about their compliance with treatment (e.g., taking this drug with food).
-Patients with very severe acne, scarring, or primary manifestations on the trunk may require 2 mg/kg/day dosing.
-Any patient requesting refills requires a new prescription and a new authorization from the iPLEDGE program.
-The safety and efficacy of once a day dosing has not been established; thus, once a day dosing is not recommended.

Use: Treatment of severe recalcitrant nodular acne in patients who are unresponsive to conventional therapy, including systemic antibiotics

What happens if I miss a dose?

Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line . Overdose symptoms may include headache, dizziness, vomiting, stomach pain, warmth or tingling in your face, swollen or cracked lips, and loss of balance or coordination.

What should I avoid while taking isotretinoin?

Do not take a vitamin or mineral supplement that contains vitamin A, unless your doctor tells you to.

Do not donate blood while taking isotretinoin and for at least 30 days after you stop taking it. Donated blood that is later given to a pregnant woman could lead to birth defects in her baby if the blood contains any level of isotretinoin.

While you are taking isotretinoin and for at least 6 months after your last dose: Do not use wax hair removers or have dermabrasion or laser skin treatments. Scarring may result.

Isotretinoin could make you sunburn more easily. Avoid sunlight or tanning beds. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Avoid driving or hazardous activity until you know how isotretinoin will affect you. Isotretinoin may impair your vision, especially at night.

What other drugs will affect isotretinoin?

Tell your doctor about all your other medicines, especially:

• phenytoin;
• St. John’s wort (may make birth control pills less effective);
• vitamin or mineral supplements;
• progestin-only birth control pills (mini-pills, may not work as well when taken with isotretinoin);
• steroid medicine; or
• a tetracycline antibiotic, including doxycycline or minocycline.

What is Krazati?

Krazati is a targeted therapy for non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) with an abnormal KRAS G12C gene. Krazati reduces tumor growth by locking the KRAS protein so it is inactive. Krazati tablets are taken twice daily.

The KRAS gene makes a protein that works like an on/off switch to control cell growth and cell death. An abnormal KRAS G12C gene it may cause cancer cells to grow and spread in the body. Krazati works by inhibiting KRAS G12C to help stop tumor growth.

Krazati FDA approval was received on December 12, 2022, for specific patients with non-small cell lung cancer, and on June 21, 2024, it received FDA approval for colorectal cancer in certain patients.

What is Krazati used to treat?

Krazati FDA approval is to treat adults with:

• non-small cell lung cancer (NSCLC) that has spread to other parts of the body or cannot be removed by surgery and has a KRAS G12C mutation determined by an FDA-approved test. Patients must have tried at least one prior systemic therapy. In NSCLC this medicine is used as a single agent.
• metastatic colorectal cancer (CRC) that has spread to other parts of the body or cannot be removed by surgery and has a KRAS G12C mutation determined by an FDA-approved test. Krazati is used in combination with Erbitux (cetuximab). Patients must already tried a prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Krazati side effects

Common Krazati side effects

Common Krazati side effects may include nausea, diarrhea, vomiting, tiredness, muscle and bone pain, liver problems, trouble breathing, loss of appetite, swelling, less urination, and feeling tired or short of breath. These side effects occurred in 25% or more patients when using this medicine for NSCLC. Changes in laboratory blood tests may also occur.

Common Krazati side effects include rash, nausea, diarrhea, vomiting, tiredness, muscle and joint pain, liver problems, headache, dry skin, abdominal pain, lower appetite, swelling, cough, and low iron blood levels. These side effects occurred in 25% or more patients when used for CRC in combination with cetuximab.

Serious Krazati side effects

Get emergency medical help if you have signs of an allergic reaction, such as hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.

Krazati may cause other serious side effects. Call your doctor at once if you have:

• nausea, diarrhea, or vomiting;
• shortness of breath, cough or fever;
• fast or pounding heartbeats, fluttering in your chest, and sudden dizziness (like you might pass out);
• stomach bleeding – bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds or
• liver problems – loss of appetite, stomach pain (upper right side), tiredness, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA .

Before taking Krazati

Before you start treatment, tell your healthcare provider about all of your medical conditions, including if you:

• have any heart problems, including heart failure and congenital long QT syndrome.
• have liver problems.

Pregnancy

This medicine may harm an unborn baby. Tell your doctor or healthcare provider if you are pregnant.

This medicine may affect fertility in men or women. Pregnancy could be harder to achieve while either parent is using this medicine.

Breastfeeding

Tell your doctor or healthcare professional if you are breastfeeding or plan to breastfeed. It is not known if this medicine passes into your breastmilk. Do not breastfeed during treatment or for one week after your last dose.

Warnings

Gastrointestinal side effects. This medicine may cause diarrhea, nausea, and vomiting. Seek medical advice. Depending on how severe your symptoms are, your dose may be reduced or permanently discontinued.

QTc Interval Prolongation: This medicine should not be used with other products with a known potential to prolong the QTc interval. If you are at risk or on medications known to prolong the QT interval, your ECG will be monitored, and electrolytes, particularly potassium and magnesium. Your healthcare provider will correct any electrolyte abnormalities.

Liver problems: Your healthcare provider will monitor liver laboratory tests prior to the start of this medicine, monthly for 3 months after, and as clinically indicated.

Lung problems: Monitor for new or worsening respiratory symptoms.

How should I take Krazati?

Take Krazati twice a day, with or without food, at the same time each day.

Swallow the tablet whole, and do not crush, chew, or break it.

If you vomit shortly after taking this medicine, do not take another dose. Take your next dose as scheduled.

If you miss a dose, take it as soon as you remember. If it has been more than 4 hours, do not take it. Take your next dose at your next scheduled time. Do not take 2 doses at the same time to make up for a missed dose.

Your treatment may be changed or permanently discontinued if you have certain side effects.

This medicine can affect the results of certain medical tests. Tell any doctor who treats you that you are using this medicine.

You will need medical tests before and during treatment with this medicine.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

If you develop certain side effects, your healthcare provider may change your dose or temporarily or permanently stop treatment.

Dosing information

Usual Adult Krazati Dose for Non-Small Cell Lung Cancer

Recommended dosage: 600 mg orally twice daily

Usual Adult Krazati Dose for Colorectal Cancer in combination with cetuximab

Recommended dosage for CRC: 600 mg orally twice daily

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verifying and describing a clinical benefit in a confirmatory trial(s).

What is Onureg?

Onureg is a prescription medicine used for continued treatment of adults with acute myeloid leukemia (AML) who:

• had a first complete remission (CR) following intensive induction chemotherapy with or without recovery of your blood cell counts, and
• who are not able to complete intensive curative therapy.

It is not known if Onureg is safe and effective in children under 18 years of age.

Warnings

Both men and women using Onureg should use effective birth control to prevent pregnancy. Azacitidine can harm an unborn baby if the mother or father is using this medicine.

Before taking this medicine

You should not use Onureg if you are allergic to azacitidine.

To make sure Onureg is safe for you, tell your doctor if you have:

• kidney disease; or
• liver disease.

Azacitidine can harm an unborn baby if the mother or the father is using this medicine.

• If you are a woman, you may need to have a negative pregnancy test before starting this treatment. Do not use Onureg if you are pregnant. Use effective birth control to prevent pregnancy while you are using this medicine. If you take Onureg, keep using birth control for at least 6 months after your last dose.
• If you are a man, use effective birth control if your sex partner is able to get pregnant. If you take Onureg, keep using birth control for at least 3 months after your last dose.
• Tell your doctor right away if a pregnancy occurs while either the mother or the father is using Onureg.

Onureg may affect fertility (ability to have children) in both men and women. However, it is important to use birth control to prevent pregnancy because this medicine can harm an unborn baby.

You should not breastfeed while using Onureg. Also do not breastfeed for at least 1 week after your last dose of Onureg.

How should I use Onureg?

Use Onureg exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets.

Onureg tablets are taken by mouth in a 28-day treatment cycle. You may need to take the medicine only during the first 2 weeks of each cycle.

Take Onureg at the same time each day, with or without food. Swallow the tablet whole and do not crush, chew, or break it.

Do not use a broken tablet. The medicine from a broken pill can be dangerous if it gets in your mouth, eyes, or nose, or on your skin. If this happens, wash your skin with soap and water or rinse your eyes with water.

If you vomit shortly after taking Onureg, do not take another dose. Wait until your next scheduled dose time to take the medicine again.

Your treatment schedule may be different. Your doctor will determine how long to treat you with azacitidine. Onureg tablets should not be used in place of Vidaza (azacitidine) injection. The oral and injection forms of this medicine have different uses and dosages.

You may also be given medicine to reduce nausea and vomiting. Use this medicine only as prescribed.

Azacitidine can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your kidney function may also need to be tested.

Store Onureg at room temperature away from moisture and heat. Keep the tablets in their original container, along with the packet or canister of moisture-absorbing preservative. Keep the container tightly closed when not in use.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What should I avoid while using Onureg?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Onureg side effects

Get emergency medical help if you have signs of an allergic reaction to Onureg: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe ongoing nausea, vomiting, or diarrhea;
• redness, swelling, warmth, oozing, or other signs of skin infection;
• low blood cell counts–fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath;
• signs of a lung infection–fever, cough with mucus, chest pain, feeling short of breath;
• kidney problems–pain in your lower back, blood in your urine, little or no urination, swelling in your feet or ankles;
• liver problems–upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
• low potassium level–leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling; or
• signs of tumor cell breakdown–tiredness, weakness, muscle cramps, nausea, vomiting, diarrhea, fast or slow heart rate, tingling in your hands and feet or around your mouth.

Common Onureg side effects may include:

• fever, chills, bruising, or other signs of low blood cell counts;
• lung infection;
• low potassium;
• nausea, vomiting, stomach pain, loss of appetite;
• constipation, diarrhea;
• joint pain, pain in your arms or legs;
• feeling weak or tired; or
• dizziness.

What is Revlimid?

Revlimid is a medication used to treat types of multiple myeloma, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, and anemia in myelodysplastic syndromes (MDS) in adults. Revlimid helps to slow cancer growth, block new blood vessel growth in tumors, and help the immune system fight cancer. Revlimid is available as capsules that are taken once a daily.

Revlimid received FDA approval on December 27, 2005. The active ingredient, sometimes called the generic name, is lenalidomide.

This medicine is only available through a restricted distribution program called the Lenalidomide REMS program, as it may cause birth defects or embryo-fetal death.

What is Revlimid used for?

Revlimid is used for specific adult patients with:

Multiple Myeloma in combination with dexamethasone. Also, for multiple myeloma maintenance therapy in patients who have had an autologous hematopoietic stem cell transplantation (auto-HSCT).

Myelodysplastic Syndromes with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.

Mantle Cell Lymphoma (MCL) that has relapsed or progressed after two prior therapies, one of which included bortezomib.

Previously treated Follicular Lymphoma (FL), used in combination with a rituximab product.

Previously treated Marginal Zone Lymphoma (MZL), used in combination with combination with a rituximab product.

Revlimid is not indicated and is not recommended for the treatment of patients with CLL outside of controlled clinical trials.

Revlimid side effects

Common Revlimid side effects may include:

• cold symptoms such as stuffy nose, sneezing, sore throat;
• sleep problems, tiredness;
• weakness;
• headache;
• tremors;
• nosebleed;
• muscle cramps;
• joint pain;
• shortness of breath;
• fever, cough, tiredness;
• itching, rash, swelling; or
• stomach pain, nausea, vomiting, diarrhea, constipation.

Serious Revlimid side effects.

Get emergency medical help if you have signs of an allergic reaction (hives, difficulty breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Lenalidomide may cause serious side effects. Call your doctor at once if you have:

• signs of a stroke or blood clot – sudden numbness or weakness, severe headache, problems with speech or vision, shortness of breath, swelling or redness in your arm or leg;
• heart attack symptoms – chest pain or pressure, pain spreading to your jaw or shoulder, sweating;
• liver problems – upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
• low blood cell counts – fever, chills, swollen gums, mouth sores, skin sores, easy bruising, unusual bleeding;
• signs of a tumor getting worse – swollen glands, low fever, rash, or pain; or
• signs of tumor cell breakdown – lower back pain, blood in your urine, little or no urinating, numbness or tingly feeling around your mouth, muscle weakness or tightness, feeling short of breath, confusion, fainting.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects.

Warnings

Never use Revlimid if you are pregnant. Even one dose of lenalidomide can cause severe, life-threatening birth defects or death of a baby if the mother or the father is taking this medicine at the time of conception or during pregnancy.

Use birth control to prevent pregnancy, whether you are a man or a woman.

For women: Use two forms of birth control, beginning 4 weeks before you start taking Revlimid and ending 4 weeks after you stop taking it. See the ‘Before taking this medicine’ section for more information.

For men: Use a condom to prevent pregnancy during your treatment and for up to 4 weeks after your treatment ends. See the ‘Before taking this medicine’ section for more information.

Revlimid may cause blood clots. Stop using this medicine and call your doctor at once if you have symptoms such as sudden numbness, severe headache, problems with vision or speech, chest pain, shortness of breath, coughing up blood, or swelling in your arm or leg.

Revlimid can lower blood cells that help your body fight infections and help your blood to clot. Call your doctor if you have unusual bruising or bleeding or signs of infection (fever, chills, body aches). You will need frequent blood tests while you are taking Revlimid.

Before taking this medicine

You should not use Revlimid if you are allergic to lenalidomide.

To make sure Revlimid is safe for you, tell your doctor if you have ever had:

• an allergic reaction to thalidomide;
• kidney disease (or if you are on dialysis);
• liver disease;
• a blood clots or stroke;
• high blood pressure, high cholesterol or triglycerides;
• a thyroid disorder;
• lactose intolerance; or
• if you smoke.

Using Revlimid may increase your risk of developing other types of cancer, such as leukemia or lymphoma. Talk with your doctor about your specific risk.

Pregnancy

Revlimid can cause severe, life-threatening birth defects or death of a baby if the mother or the father is taking this medicine at the time of conception or during pregnancy. Even one dose of lenalidomide can cause major birth defects in the baby’s arms and legs, bones, ears, eyes, face, and heart. Never use Revlimid if you are pregnant. Tell your doctor right away if your period is late while taking Revlimid.

For Women: If you have not had a hysterectomy, you will be required to use two reliable forms of birth control, beginning 4 weeks before you start taking Revlimid and ending 4 weeks after you stop taking it. Even women with fertility problems are required to use birth control while taking this medicine. You must also have a negative pregnancy test 10 to 14 days before treatment and again 24 hours before. While you are taking Revlimid, you will have a pregnancy test every 2 to 4 weeks.

The birth control method you use must be proven highly effective, such as birth control pills, an intrauterine device (IUD), a tubal ligation, or a sexual partner’s vasectomy. The extra form of birth control you use must be a barrier method such as a latex condom, a diaphragm, or a cervical cap.

Stop using Revlimid and call your doctor at once if you quit using birth control, if your period is late, or if you think you might be pregnant. Not having sexual intercourse (abstinence) is the most effective method of preventing pregnancy.

For Men: If a man fathers a baby while using Revlimid, the baby may have birth defects. Use a condom to prevent pregnancy during your treatment and for up to 4 weeks after your treatment ends. You must agree in writing to always use latex condoms when having sex with a woman who is able to get pregnant, even if you have had a vasectomy. Contact your doctor if you have had unprotected sex, even once, or if you think your female sexual partner may be pregnant.

Breastfeeding

You should not breastfeed while using Revlimid.

How should I take Revlimid?

Take the medicine at the same time each day. You may take Revlimid with or without food.

Take each dose with a full glass of water. Swallow the capsule whole without breaking it open.

Lenalidomide can increase your risk of bleeding or infection. Your blood will need to be tested often.

Medicine from an open capsule can be dangerous if it gets on your skin. If this occurs, wash your skin with soap and water. Ask your doctor or pharmacist how to handle and dispose of a broken capsule safely.

Take Revlimid exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or longer than recommended. Never share this medicine with another person, even if they have the same disorder you have.

Revlimid Dosing information

Usual Adult Revlimid Dose for Multiple Myeloma

Use: Multiple Myeloma in combination with dexamethasone
Dose: 25 mg orally once a day on Days 1 to 21 of repeated 28-day cycles until disease progression or unacceptable toxicity

Use: Maintenance therapy for Multiple Myeloma following auto-HSCT
Dose: 10 mg once a day continuously (Days 1 to 28 of repeated 28-day cycles) for 3 cycles, then increase to 15 mg once a day if tolerated until disease progression or unacceptable toxicity.

Comments:
For patients who are not eligible for auto-HSCT, therapy should continue until disease progression or unacceptable toxicity.
For patients who are eligible for auto-HSCT, hematopoietic stem cell mobilization should occur within 4 cycles.
Following auto-HSCT, initiate maintenance therapy after adequate hematologic recovery (ANC 1000/mcL or more AND/OR platelet count 75,000/mcL or more).
Consult the manufacturer’s product information for dexamethasone dosing recommendations.

Usual Adult Dose for Myelodysplastic Disease:

Dose: 10 mg orally once a day; therapy is continued or modified based on clinical and laboratory findings until disease progression or unacceptable toxicity
Use: Treatment of transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.

Usual Adult Dose for Lymphoma:

Follicular Lymphoma or Marginal Zone Lymphoma:
Dose: 20 mg orally once a day on Days 1 through 21 of repeated 28-day cycles for up to 12 cycles in combination with a rituximab product.
Use: In combination with a rituximab product for the treatment of previously treated follicular lymphoma (FL). In combination with a rituximab product for the treatment of previously treated marginal zone lymphoma (MZL).

Mantel Cell Lymphoma:
Dose: 25 mg orally once a day on Days 1 to 21 of repeated 28-day cycles until disease progression or unacceptable toxicity; treatment is continued, modified, or discontinued based on clinical and laboratory findings.
Use: The treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after 2 prior therapies, one of which included bortezomib.

Revlimid is available in 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg capsules.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If you are more than 12 hours late, skip the missed dose. Do not take extra medicine to make up for the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What to avoid

You must not donate blood or sperm while you are using Revlimid, and for at least 4 weeks after your last dose. Avoid exposing another person to your blood or semen through casual or sexual contact.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient’s body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

What other drugs will affect Revlimid?

Tell your doctor if you also use pembrolizumab (Keytruda).

If you use hormonal birth control (pills, implants, injections) to prevent pregnancy: There are certain drugs that can make hormonal birth control less effective in your body. Tell your doctor about all other medicines you use. You may need to replace your hormonal birth control method with another effective form of contraception.

Other drugs may interact with lenalidomide, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Revlimid Package Insert

Review the Revlimid Package Insert for more detailed information about this medicine. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

Handling and Disposal

Care should be exercised in the handling of this medicine. Capsules should not be opened or broken. If powder from capsules contacts the skin, wash the skin immediately and thoroughly with soap and water. If Revlimid contacts the mucous membranes, flush thoroughly with water. Procedures for the proper handling and disposal of anticancer drugs should be considered. Several guidelines on the subject have been published. Dispense no more than a 28-day supply.

Ingredients

Active ingredient: lenalidomide

Inactive ingredients: lactose anhydrous, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate.

The 5 mg and 25 mg capsule shells contain gelatin, titanium dioxide, and black ink.

The 2.5 mg and 10 mg capsule shells contain gelatin, FD&C blue #2, yellow iron oxide, titanium dioxide, and black ink.

The 15 mg capsule shell contains gelatin, FD&C blue #2, titanium dioxide, and black ink.

The 20 mg capsule shell contains gelatin, FD&C blue #2, yellow iron oxide, titanium dioxide and black ink.

Storage

Store at 20°C – 25°C (68°F – 77°F)

What is abiraterone?

Abiraterone works by reducing androgen production in the body. Androgens are male hormones that can promote tumor growth in the prostate gland.

Abiraterone is used together with steroid medication (prednisone or methylprednisolone) to treat prostate cancer that has spread to other parts of the body. abiraterone is used in men whose prostate cancer cannot be treated with surgery or other medicines.

It is not known if abiraterone acetate tablets are safe or effective in females or children.

Warnings

Abiraterone tablets should not be handled by a woman who is pregnant or who may become pregnant. This medicine can harm an unborn baby or cause miscarriage.You should not use abiraterone if you are allergic to it.

Before taking this medicine

Abiraterone is not for use by women or children.

To make sure this medicine is safe for you, tell your doctor if you have ever had:

• liver disease;
• diabetes (especially if you use pioglitazone or repaglinide);
• heart problems, high blood pressure;
• a heart attack;
• low levels of potassium in your blood; or
• problems with your adrenal gland or pituitary gland.

Abiraterone can harm an unborn baby if a woman is exposed to it during pregnancy. An abiraterone tablet should not be handled by a woman who is pregnant or may become pregnant. The medicine from a broken tablet could be absorbed through the skin.

Abiraterone can also harm an unborn baby if the father is taking this medicine at the time of conception or during pregnancy.

Use effective birth control if your sex partner is pregnant or able to get pregnant. Keep using birth control for at least 3 weeks after your last dose.

How should I take abiraterone?

Take abiraterone exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets.

Abiraterone is usually taken once per day while also taking a steroid 1 or 2 times per day. Follow your doctor’s dosing instructions very carefully.

Your abiraterone dose needs may change if you switch to a different brand, strength, or form of this medicine. Avoid medication errors by using only the medicine your doctor prescribes.

Your prednisone or methylprednisolone dose needs may change if you have an infection or are under stress. Do not change your dose or stop using your steroid medicine without your doctor’s advice.

Take this medicine with a full glass of water.

You may take Yonsa with or without food.

Take Zytiga on an empty stomach. Do not eat anything for at least 2 hours before and 1 hour after you take Zytiga.

Swallow the tablet whole and do not crush, chew, or break it.

Your blood pressure will need to be checked often, and you may need frequent blood tests. If you have diabetes, your blood sugar should be checked carefully, especially if you take pioglitazone or repaglinide.

You should not stop using abiraterone or your steroid medicine suddenly. Follow your doctor’s instructions about tapering your prednisone dose.

Store at room temperature away from moisture and heat.

Dosing information

Usual Adult Dose for Prostate Cancer:

Metastatic CRPC:
-Regular formulation: 1000 mg orally once daily (in combination with methylprednisolone 5 mg orally 2 times daily)
-Micronized formulation: 500 mg orally once daily (in combination with methylprednisolone 4 mg orally 2 times daily)

Metastatic high-risk CSPC:
-Regular formulation: 1000 mg orally once daily (in combination with methylprednisolone 5 mg orally once daily)
-Micronized formulation: 500 mg orally once daily (in combination with methylprednisolone 4 mg orally 2 times a day)

Comments:
-Patients receiving this drug should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
NOTE: Different abiraterone acetate formulations have different indications and different dosing. Below are suggested dosing guidelines. Refer to the manufacturer product information before prescribing this drug.

Uses:
In combination with prednisone for the treatment of patients with:
-Metastatic castration-resistant prostate cancer (CRPC)
-Metastatic high-risk castration-sensitive prostate cancer (CSPC)

Detailed Abiraterone dosage information

What happens if I miss a dose?

Skip the missed dose and take the medicine the following day. Do not take two doses at one time.

Call your doctor for instructions if you miss more than one dose of abiraterone.

What should I avoid while taking abiraterone?

Do not eat food for at least 2 hours before you take Zytiga and for at least 1 hour after your dose. Food can increase the amount of Zytiga your body absorbs and may cause side effects.

Avoid taking an herbal supplement containing St. John’s wort.

Abiraterone side effects

Get emergency medical help if you have signs of an allergic reaction to abiraterone: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• swelling in your ankles or feet, pain in your legs;
• fast or irregular heartbeats;
• a light-headed feeling, like you might pass out;
• severe headache, blurred vision, pounding in your neck or ears;
• pain or burning when you urinate;
• low red blood cells (anemia) – pale skin, tiredness, feeling light-headed or short of breath, cold hands and feet;
• low blood potassium – leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling;
• liver problems – stomach pain (upper right side), nausea, vomiting, dark urine, jaundice (yellowing of the skin or eyes); or
• low blood sugar – headache, hunger, sweating, irritability, dizziness, fast heart rate, and feeling anxious or shaky.

Common abiraterone side effects may include:

• feeling very weak or tired;
• feeling very hot;
• high blood sugar;
• increased blood pressure;
• swelling in your legs or feet;
• anemia, low blood potassium;
• painful urination;
• abnormal liver function tests or other blood tests;
• joint pain or swelling;
• headache;
• nausea, vomiting, diarrhea; or
• cold symptoms such as stuffy nose, sneezing, cough, sore throat.

What is abiraterone?

Abiraterone works by reducing androgen production in the body. Androgens are male hormones that can promote tumor growth in the prostate gland.

Abiraterone is used together with steroid medication (prednisone or methylprednisolone) to treat prostate cancer that has spread to other parts of the body. abiraterone is used in men whose prostate cancer cannot be treated with surgery or other medicines.

It is not known if abiraterone acetate tablets are safe or effective in females or children.

Warnings

Abiraterone tablets should not be handled by a woman who is pregnant or who may become pregnant. This medicine can harm an unborn baby or cause miscarriage.You should not use abiraterone if you are allergic to it.

Before taking this medicine

Abiraterone is not for use by women or children.

To make sure this medicine is safe for you, tell your doctor if you have ever had:

• liver disease;
• diabetes (especially if you use pioglitazone or repaglinide);
• heart problems, high blood pressure;
• a heart attack;
• low levels of potassium in your blood; or
• problems with your adrenal gland or pituitary gland.

Abiraterone can harm an unborn baby if a woman is exposed to it during pregnancy. An abiraterone tablet should not be handled by a woman who is pregnant or may become pregnant. The medicine from a broken tablet could be absorbed through the skin.

Abiraterone can also harm an unborn baby if the father is taking this medicine at the time of conception or during pregnancy.

Use effective birth control if your sex partner is pregnant or able to get pregnant. Keep using birth control for at least 3 weeks after your last dose.

How should I take abiraterone?

Take abiraterone exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets.

Abiraterone is usually taken once per day while also taking a steroid 1 or 2 times per day. Follow your doctor’s dosing instructions very carefully.

Your abiraterone dose needs may change if you switch to a different brand, strength, or form of this medicine. Avoid medication errors by using only the medicine your doctor prescribes.

Your prednisone or methylprednisolone dose needs may change if you have an infection or are under stress. Do not change your dose or stop using your steroid medicine without your doctor’s advice.

Take this medicine with a full glass of water.

You may take Yonsa with or without food.

Take Zytiga on an empty stomach. Do not eat anything for at least 2 hours before and 1 hour after you take Zytiga.

Swallow the tablet whole and do not crush, chew, or break it.

Your blood pressure will need to be checked often, and you may need frequent blood tests. If you have diabetes, your blood sugar should be checked carefully, especially if you take pioglitazone or repaglinide.

You should not stop using abiraterone or your steroid medicine suddenly. Follow your doctor’s instructions about tapering your prednisone dose.

Store at room temperature away from moisture and heat.

Dosing information

Usual Adult Dose for Prostate Cancer:

Metastatic CRPC:
-Regular formulation: 1000 mg orally once daily (in combination with methylprednisolone 5 mg orally 2 times daily)
-Micronized formulation: 500 mg orally once daily (in combination with methylprednisolone 4 mg orally 2 times daily)

Metastatic high-risk CSPC:
-Regular formulation: 1000 mg orally once daily (in combination with methylprednisolone 5 mg orally once daily)
-Micronized formulation: 500 mg orally once daily (in combination with methylprednisolone 4 mg orally 2 times a day)

Comments:
-Patients receiving this drug should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
NOTE: Different abiraterone acetate formulations have different indications and different dosing. Below are suggested dosing guidelines. Refer to the manufacturer product information before prescribing this drug.

Uses:
In combination with prednisone for the treatment of patients with:
-Metastatic castration-resistant prostate cancer (CRPC)
-Metastatic high-risk castration-sensitive prostate cancer (CSPC)

What happens if I miss a dose?

Skip the missed dose and take the medicine the following day. Do not take two doses at one time.

Call your doctor for instructions if you miss more than one dose of abiraterone.

What should I avoid while taking abiraterone?

Do not eat food for at least 2 hours before you take Zytiga and for at least 1 hour after your dose. Food can increase the amount of Zytiga your body absorbs and may cause side effects.

Avoid taking an herbal supplement containing St. John’s wort.

Abiraterone side effects

Get emergency medical help if you have signs of an allergic reaction to abiraterone: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• swelling in your ankles or feet, pain in your legs;
• fast or irregular heartbeats;
• a light-headed feeling, like you might pass out;
• severe headache, blurred vision, pounding in your neck or ears;
• pain or burning when you urinate;
• low red blood cells (anemia) – pale skin, tiredness, feeling light-headed or short of breath, cold hands and feet;
• low blood potassium – leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling;
• liver problems – stomach pain (upper right side), nausea, vomiting, dark urine, jaundice (yellowing of the skin or eyes); or
• low blood sugar – headache, hunger, sweating, irritability, dizziness, fast heart rate, and feeling anxious or shaky.

Common abiraterone side effects may include:

• feeling very weak or tired;
• feeling very hot;
• high blood sugar;
• increased blood pressure;
• swelling in your legs or feet;
• anemia, low blood potassium;
• painful urination;
• abnormal liver function tests or other blood tests;
• joint pain or swelling;
• headache;
• nausea, vomiting, diarrhea; or
• cold symptoms such as stuffy nose, sneezing, cough, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect abiraterone?

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Tell your doctor about all your current medicines. Many drugs can interact with abiraterone, especially:

• other prostate cancer medicines, especially radium Ra 223 (may increase your risk of fractures while you are taking abiraterone); or
• pioglitazone or repaglinide to treat diabetes (may cause severe low blood sugar hypoglycemia while you are taking abiraterone.

What is Abecma?

Abecma is a CAR T cell therapy used to treat relapsed or refractory multiple myeloma to help patients live longer without cancer progressing or passing away. Abecma infusion is made from your white blood cells, which are changed so that they can recognize and kill multiple myeloma cancer cells. It is given as a one-time infusion after the process of making your personal infusion.

Abecma FDA approval was granted on March 26, 2021, for adult patients who have relapsed or refractory multiple myeloma and have tried two or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an antiCD38 monoclonal antibody.  Abecma approval was based on positive results from KarMMa Pivotal Trial that showed 72% idecabtagene vicleucel treated patients had a response that was a partial response (19%), very good partial response (25%), or stringent complete response (28%). 

Abecma mechanism of action (MOA) is as a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell immunotherapy.

How does Abecma work?

Abecma (idecabtagene vicleucel) is a medicine made from your own white blood cells, which are genetically modified so that they can recognize and attack your multiple myeloma cells. Abecma Car T therapy works as your T cells (a type of white blood cell) are changed to recognize proteins on the outside MM cancer cells so that they can attack the cancer cells. A more detailed explanation of how it works is:

• Your T cells are a type of white blood cell that is part of your immune system that can attack foreign substances in your body.
• On the outside of the multiple myeloma cells are proteins called B-cell maturation antigen (BCMA).
• Normally, T cells do not recognize MM cells, so do not attack and kill them.
• Your T cells (type of white blood cell) are collected and sent to the manufacturing center where they add to the T cell a special receptor called CAR (chimeric antigen receptor) that is designed to bind to certain proteins in cancer cells.
• Your T Cells will now be able to recognize the BCMA protein on the MM cells and kill the cancer cells.
• These changed T cells, called chimeric antigen receptor T cells (CAR T cells), are then grown in large numbers in the laboratory and then given as a one-time Abecma infusion to the MM cancer patient.

BCMA = B-cell maturation antigen. CAR-T = chimeric antigen receptor-T cell.

How will I receive Abecma?

Abecma is made from your own white blood cells, so your blood will be collected by a process called “leukapheresis” (LOO-kuh-feh-REE-sis). This is when they take blood from your bloodstream and separate white blood cells from the rest of your blood, which they return to the bloodstream.

Your white blood cells will be sent to a manufacturing center to make your infusion, which usually takes about 4 weeks, but the time may vary.

Before you have your infusion, you will be given chemotherapy for 3 days to prepare your body.

You are usually given Abecma 2 days after completion of chemotherapy.

Abecma is given as an intravenous infusion through a catheter (tube) placed into your vein. Your dose may be given in one or more infusion bags. The infusion usually takes up to 30 minutes for each infusion bag.

Approximately 30 to 60 minutes before your infusion, you will be given an antihistamine and acetaminophen.

You will be monitored at the certified healthcare facility, where you will receive your treatment daily for at least 7 days after the infusion.

You should plan to stay within 2 hours of this location for at least 4 weeks after getting Abecma. Your healthcare provider will check to see that your treatment is working and help you with any side effects that may occur.

Your infusion may be delayed up to 7 days if you have any of the following conditions:

• unresolved serious adverse events (especially pulmonary events, cardiac events, or hypotension), including those after preceding chemotherapies,
• active infections, or inflammatory disorders.

Warnings

Abecma can cause a very common side effect called cytokine release syndrome or CRS, which can be severe or fatal. Symptoms of CRS include fever, difficulty breathing, dizziness or light-headedness, nausea, headache, fast heartbeat, low blood pressure, or fatigue. Tell your healthcare provider right away if you develop fever or any of these other symptoms.

Abecma can increase the risk of life-threatening infections that may lead to death. Tell your healthcare provider right away if you develop fever, chills, or any signs or symptoms of an infection. It may also lower one or more types of blood cells (red blood cells, white blood cells, or platelets), which may make you feel weak or tired or increase your risk of severe infection or bleeding. After treatment, your healthcare provider will test your
blood to check for this. Tell your healthcare provider right away if you get a fever, are feeling tired, or have bruising or bleeding.

Abecma may increase your risk of getting cancer including certain types of blood cancers, called T-cell malignancies. Your healthcare provider should monitor you for these.

Abecma may also cause life-threatening nerve problems, blood disorders, or other life-threatening reactions. Tell your caregivers or seek emergency medical attention if you have problems with speech, problems with thinking or memory, confusion, seizures, fatigue, shortness of breath, or chest pain.

Having Abecma in your blood may cause a false-positive human immunodeficiency virus (HIV) test result by some commercial tests.

It is important that you tell your healthcare providers that you have received Abecma and to show them your Patient Wallet Card. Your healthcare provider may give you other medicines to treat your side effects.

Before taking this medicine

Tell your doctor if you have ever had:

• an active infection or inflammation;
• hepatitis B;
• cytomegalovirus; or
• if you have received a vaccine in the past 6 weeks.

Pregnancy

This medicine is not recommended for women who are pregnant, and pregnancy after Abecma infusion should be discussed with the treating physician. Women may need to take a pregnancy test before receiving this medicine. You may also need to use birth control to prevent pregnancy during and shortly after treatment with Abecma and chemotherapy.

Assess immunoglobulin levels in newborns of mothers treated with this infusion. If you receive the infusion during pregnancy, your baby’s blood may need to be tested after it is born. This is to evaluate any effects the medicine may have had on the baby.

Breastfeeding

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risks.

What should I avoid while using Abecma?

Abecma can cause weakness, drowsiness, confusion, problems with memory or coordination, and seizures. Avoid driving or operating machinery for at least 8 weeks after you are have your infusion.

Vaccination with live virus vaccines is not recommended for at least 6 weeks before the start of lymphodepleting chemotherapy, during Abecma treatment, and until immune recovery following your infusion.

Do not donate blood, an organ, or any tissues or cells.

Abecma REMS

Abecma is only available through a restricted program called the Abecma REMS (Risk Evaluation and Mitigation Strategy) program designed to manage the risk of serious side effects. The Abecma REMS program aims to reduce  the risks of cytokine release syndrome (CRS) and neurologic toxicities. This infusion can only be administered at a REMS-certified healthcare facility that is specially certified and has on-site, immediate access to treatments (tocilizumab) and facilities that may be required.

What other drugs will affect Abecma?

Other drugs may interact with Abecma, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Does Abecma interact with my other drugs?

Enter medications to view a detailed interaction report using our Drug Interaction Checker.Drug nameAdd a drug to check interactionsAdd

Storage

• Store Abecma frozen in the vapor phase of liquid nitrogen (less than or equal to minus 130°C).
• Thaw Abecma prior to the infusion, according to the Prescribing Information.

Ingredients

Abecma is supplied in one or more infusion bag(s) containing a frozen suspension of genetically modified autologous T cells in 5% DMSO.

Abecma is made specifically for each individual patient with their own white blood cells. Match the identity of the patient with the patient identifiers on the cassette(s) and infusion bag(s) upon receipt.

Highlights of Prescribing Information

These highlights do not include all the information needed to use ABIRATERONE ACETATE TABLETS safely and effectively. See full prescribing information for ABIRATERONE ACETATE TABLETS.

ABIRATERONE ACETATE tablets, for oral use
Initial U.S. Approval: 2011

Recent Major Changes

Indications and Usage for Abiraterone Acetate

Abiraterone acetate tablets are a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with•metastatic castration-resistant prostate cancer (CRPC). •metastatic high-risk castration-sensitive prostate cancer (CSPC).

Abiraterone Acetate Dosage and Administration

Metastatic castration-resistant prostate cancer:•Abiraterone acetate tablets 1,000 mg orally once daily with prednisone
5 mg orally twice daily.

Metastatic castration-sensitive prostate cancer:•Abiraterone acetate tablets 1,000 mg orally once daily with prednisone
5 mg orally once daily.

Patients receiving abiraterone acetate tablets should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. Abiraterone acetate tablets must be taken as a single dose once daily on an empty stomach. Do not eat food 2 hours before and 1 hour after taking Abiraterone acetate tablets. The tablets must be swallowed whole with water. Do not crush or chew tablets.

Dose Modification:•For patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the abiraterone acetate tablets starting dose to 250 mg once daily. (2.4)•For patients who develop hepatotoxicity during treatment, hold abiraterone acetate tablets until recovery. Retreatment may be initiated at a reduced dose. Abiraterone acetate tablets should be discontinued if patients develop severe hepatotoxicity.

Dosage Forms and Strengths

•Uncoated Tablet 250 mg

Contraindications

• None (4)

Warnings and Precautions

•Mineralocorticoid excess: Closely monitor patients with cardiovascular disease. Control hypertension and correct hypokalemia before treatment. Monitor blood pressure, serum potassium and symptoms of fluid retention at least monthly. (5.1)•Adrenocortical insufficiency: Monitor for symptoms and signs of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations. (5.2)•Hepatotoxicity: Can be severe and fatal. Monitor liver function and modify, interrupt, or discontinue abiraterone acetate dosing as recommended. (5.3)•Increased fractures and mortality in combination with radium Ra 223 dichloride: Use of abiraterone acetate tablets plus prednisone/prednisolone in combination with radium Ra 223 dichloride is not recommended. (5.4)•Embryo-Fetal Toxicity: abiraterone acetate tablets can cause fetal harm. Advise males with female partners of reproductive potential to use effective contraception. (5.5, 8.1, 8.3)•Hypoglycemia: Severe hypoglycemia has been reported in patients with pre-existing diabetes who are taking medications containing thiazolidinediones (including pioglitazone) or repaglinide. Monitor blood glucose in patients with diabetes and assess if antidiabetic agent dose modifications are required. (5.6)

Adverse Reactions/Side Effects

The most common adverse reactions (≥10%) are fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache. (6.1)

The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, and hypokalemia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-233-2001 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

•CYP3A4 Inducers: Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate dosing frequency. (2.5, 7.1)•CYP2D6 Substrates: Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate. (7.2)

Use In Specific Populations

•Do not use abiraterone acetate in patients with baseline severe hepatic impairment (Child-Pugh Class C). (8.6)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 11/2024

Full Prescribing Information

1. Indications and Usage for Abiraterone Acetate

Abiraterone acetate tablets are indicated in combination with prednisone for the treatment of patients with•Metastatic castration-resistant prostate cancer (CRPC)•Metastatic high-risk castration-sensitive prostate cancer (CSPC)

2. Abiraterone Acetate Dosage and Administration

2.1 Recommended Dose for Metastatic CRPC

The recommended dose of abiraterone acetate tablets is 1,000 mg (four 250 mg tablets) orally once daily with prednisone 5 mg orally twice daily.

2.2 Recommended Dose for Metastatic High-risk CSPC

The recommended dose of abiraterone acetate tablets is 1,000 mg (four 250 mg tablets) orally once daily with prednisone 5 mg administered orally once daily.

2.3 Important Administration Instructions

Patients receiving abiraterone acetate tablets should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

Abiraterone acetate tablets must be taken as a single dose once daily on an empty stomach. Do not eat food 2 hours before and 1 hour after taking Abiraterone acetate tablets. The tablets must be swallowed whole with water. Do not crush or chew tablets.

2.4 Dose Modification Guidelines in Hepatic Impairment and Hepatotoxicity

Hepatic Impairment

In patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the recommended dose of abiraterone acetate tablets to 250 mg once daily. In patients with moderate hepatic impairment monitor ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. If elevations in ALT and/or AST greater than 5 x upper limit of normal (ULN) or total bilirubin greater than 3 x ULN occur in patients with baseline moderate hepatic impairment, discontinue abiraterone acetate tablets and do not re-treat patients with abiraterone acetate tablets.

Do not use abiraterone acetate tablets in patients with baseline severe hepatic impairment (Child-Pugh Class C).

Hepatotoxicity

For patients who develop hepatotoxicity during treatment with abiraterone acetate tablets (ALT and/or AST greater than
5 x ULN or total bilirubin greater than 3 x ULN), interrupt treatment with abiraterone acetate tablets [see Warnings and Precautions (5.3)]. Treatment may be restarted at a reduced dose of 750 mg once daily following return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5 x ULN and total bilirubin less than or equal to 1.5 x ULN. For patients who resume treatment, monitor serum transaminases and bilirubin at a minimum of every two weeks for three months and monthly thereafter.

If hepatotoxicity recurs at the dose of 750 mg once daily, re-treatment may be restarted at a reduced dose of 500 mg once daily following return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5 x ULN and total bilirubin less than or equal to 1.5 x ULN.

If hepatotoxicity recurs at the reduced dose of 500 mg once daily, discontinue treatment with abiraterone acetate tablets.

Permanently discontinue abiraterone acetate tablets for patients who develop a concurrent elevation of ALT greater than
3 x ULN and total bilirubin greater than 2 x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation .

2.5 Dose Modification Guidelines for Strong CYP3A4 Inducers

Avoid concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) during abiraterone acetate tablets treatment.

If a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate tablets dosing frequency to twice a day only during the co-administration period (e.g., from 1,000 mg once daily to 1,000 mg twice a day). Reduce the dose back to the previous dose and frequency, if the concomitant strong CYP3A4 inducer is discontinued.

3. Dosage Forms and Strengths

Abiraterone acetate tablets 250 mg are white to off-white, oval-shaped tablets debossed with “WW597” on one side.

4. Contraindications

None.

5. Warnings and Precautions

5.1 Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions due to Mineralocorticoid Excess

Abiraterone acetate may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment with abiraterone acetate.

In the combined data from 4 placebo-controlled trials using prednisone 5 mg twice daily in combination with 1,000 mg abiraterone acetate daily, grades 3-4 hypokalemia were detected in 4% of patients on the abiraterone acetate arm and 2% of patients on the placebo arm. Grades 3-4 hypertension were observed in 2% of patients each arm and grades 3-4 fluid retention in 1% of patients each arm.

In LATITUDE (a randomized placebo-controlled, multicenter clinical trial), which used prednisone 5 mg daily in combination with 1,000 mg abiraterone acetate daily, grades 3-4 hypokalemia were detected in 10% of patients on the abiraterone acetate arm and 1% of patients on the placebo arm, grades 3-4 hypertension were observed in 20% of patients on the abiraterone acetate arm and 10% of patients on the placebo arm. Grades 3-4 fluid retention occurred in 1% of patients each arm .

Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, such as those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia. In postmarketing experience, QT prolongation and Torsades de Pointes have been observed in patients who develop hypokalemia while taking abiraterone acetate.

The safety of abiraterone acetate in patients with left ventricular ejection fraction <50% or New York Heart Association (NYHA) Class III or IV heart failure (in COU-AA-301) or NYHA Class II to IV heart failure (in COU-AA-302 and LATITUDE) has not been established because these patients were excluded from these randomized clinical trials .

5.2 Adrenocortical Insufficiency

Adrenal insufficiency occurred in 0.3% of 2230 patients taking abiraterone acetate and in 0.1% of 1763 patients taking placebo in the combined data of randomized, placebo-controlled clinical studies. Adrenocortical insufficiency was reported in patients receiving abiraterone acetate in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress.

Monitor patients for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress.

Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with abiraterone acetate. If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations .

5.3 Hepatotoxicity

In postmarketing experience, there have been abiraterone acetate-associated severe hepatic toxicity, including fulminant hepatitis, acute liver failure and deaths .

In the combined data of randomized clinical trials, grade 3-4 ALT or AST increases (at least 5 x ULN) were reported in 6% of 2230 patients who received abiraterone acetate, typically during the first 3 months after starting treatment. Patients whose baseline ALT or AST were elevated were more likely to experience liver test elevation than those beginning with normal values. Treatment discontinuation due to ALT and AST increases or abnormal hepatic function occurred in 1.1% of 2230 patients taking abiraterone acetate. In these clinical trials, no deaths clearly related to abiraterone acetate were reported due to hepatotoxicity events.

Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with abiraterone acetate, every two weeks for the first three months of treatment and monthly thereafter. In patients with baseline moderate hepatic impairment receiving a reduced abiraterone acetate dose of 250 mg, measure ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the ULN, or the bilirubin rises above three times the ULN, interrupt abiraterone acetate treatment and closely monitor liver function.

Re-treatment with abiraterone acetate at a reduced dose level may take place only after return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5 x ULN and total bilirubin less than or equal to 1.5 x ULN .

Permanently discontinue abiraterone acetate for patients who develop a concurrent elevation of ALT greater than 3 x ULN and total bilirubin greater than 2 x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation .

The safety of abiraterone acetate re-treatment of patients who develop AST or ALT greater than or equal to 20 x ULN and/or bilirubin greater than or equal to 10 x ULN is unknown.

5.4 Increased Fractures and Mortality in Combination with Radium Ra 223 Dichloride

Abiraterone acetate plus prednisone/prednisolone is not recommended for use in combination with radium Ra 223 dichloride outside of clinical trials.

The clinical efficacy and safety of concurrent initiation of abiraterone acetate plus prednisone/prednisolone and radium Ra 223 dichloride was assessed in a randomized, placebo-controlled multicenter study (ERA-223 trial) in 806 patients with asymptomatic or mildly symptomatic castration-resistant prostate cancer with bone metastases. The study was unblinded early based on an Independent Data Monitoring Committee recommendation.

At the primary analysis, increased incidences of fractures (28.6% vs 11.4%) and deaths (38.5% vs 35.5%) have been observed in patients who received abiraterone acetate plus prednisone/prednisolone in combination with radium Ra 223 dichloride compared to patients who received placebo in combination with abiraterone acetate plus prednisone/prednisolone.

5.5 Embryo-Fetal Toxicity

The safety and efficacy of abiraterone acetate have not been established in females. Based on animal reproductive studies and mechanism of action, abiraterone acetate can cause fetal harm and loss of pregnancy when administered to a pregnant female. In animal reproduction studies, oral administration of abiraterone acetate to pregnant rats during organogenesis caused adverse developmental effects at maternal exposures approximately ≥ 0.03 times the human exposure (AUC) at the recommended dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with abiraterone acetate and for 3 weeks after the last dose of abiraterone acetate .

5.6 Hypoglycemia

Severe hypoglycemia has been reported when abiraterone acetate was administered to patients with pre-existing diabetes receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide [. Monitor blood glucose in patients with diabetes during and after discontinuation of treatment with abiraterone acetate. Assess if antidiabetic drug dosage needs to be adjusted to minimize the risk of hypoglycemia.

6. Adverse Reactions/Side Effects

The following are discussed in more detail in other sections of the labeling:•Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions due to Mineralocorticoid Excess 

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Two randomized placebo-controlled, multicenter clinical trials (COU-AA-301 and COU-AA-302) enrolled patients who had metastatic CRPC in which abiraterone acetate was administered orally at a dose of 1,000 mg daily in combination with prednisone 5 mg twice daily in the active treatment arms. Placebo plus prednisone 5 mg twice daily was given to patients on the control arm. Another randomized placebo-controlled, multicenter clinical trial (LATITUDE) enrolled patients who had metastatic high-risk CSPC in which abiraterone acetate was administered at a dose of 1,000 mg daily in combination with prednisone 5 mg once daily. Placebos were administered to patients in the control arm. Additionally, two other randomized, placebo-controlled trials were conducted in patients with metastatic CRPC. The safety data pooled from 2230 patients in randomized controlled trials constitute the basis for the data presented in the Warnings and Precautions, Grade 1-4 adverse reactions, and Grade 1-4 laboratory abnormalities. In all trials, a gonadotropin-releasing hormone (GnRH) analog or prior orchiectomy was required in both arms.

In the pooled data, median treatment duration was 11 months (0.1, 43) for abiraterone acetate-treated patients and 7.2 months (0.1, 43) for placebo-treated patients. The most common adverse reactions (≥10%) that occurred more commonly (>2%) in the abiraterone acetate arm were fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache. The most common laboratory abnormalities (>20%) that occurred more commonly (≥2%) in the abiraterone acetate arm were anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, and hypokalemia. Grades 3-4 adverse events were reported for 53% of patients in the abiraterone acetate arm and 46% of patients in the placebo arm. Treatment discontinuation was reported in 14% of patients in the abiraterone acetate arm and 13% of patients in the placebo arm. The common adverse events (≥1%) resulting in discontinuation of abiraterone acetate and prednisone were hepatotoxicity and cardiac disorders.

Deaths associated with treatment-emergent adverse events were reported for 7.5% of patients in the abiraterone acetate arm and 6.6% of patients in the placebo arm. Of the patients in the abiraterone acetate arm, the most common cause of death was disease progression (3.3%). Other reported causes of death in ≥5 patients included pneumonia, cardio-respiratory arrest, death (no additional information), and general physical health deterioration.

COU-AA-301: Metastatic CRPC Following Chemotherapy

COU-AA-301 enrolled 1195 patients with metastatic CRPC who had received prior docetaxel chemotherapy. Patients were not eligible if AST and/or ALT ≥2.5 x ULN in the absence of liver metastases. Patients with liver metastases were excluded if AST and/or ALT >5 x ULN.

Table 1 shows adverse reactions on the abiraterone acetate arm in COU-AA-301 that occurred with a ≥2% absolute increase in frequency compared to placebo or were events of special interest. The median duration of treatment with abiraterone acetate with prednisone was 8 months.

Table 1: Adverse Reactions due to Abiraterone Acetate in COU-AA-301

Table 2 shows laboratory abnormalities of interest from COU-AA-301.

Table 2: Laboratory Abnormalities of Interest in COU-AA-301

COU-AA-302: Metastatic CRPC Prior to Chemotherapy

COU-AA-302 enrolled 1088 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy. Patients were ineligible if AST and/or ALT ≥2.5 x ULN and patients were excluded if they had liver metastases.

Table 3 shows adverse reactions on the abiraterone acetate arm in COU-AA-302 that occurred in ≥5% of patients with a ≥2% absolute increase in frequency compared to placebo. The median duration of treatment with abiraterone acetate with prednisone was 13.8 months.

Table 3: Adverse Reactions in ≥5% of Patients on the Abiraterone Acetate Arm in COU-AA-302

Table 4 shows laboratory abnormalities that occurred in greater than 15% of patients, and more frequently (>5%) in the abiraterone acetate arm compared to placebo in COU-AA-302.

Table 4: Laboratory Abnormalities in >15% of Patients in the Abiraterone Acetate Arm of COU-AA-302

LATITUDE: Patients with Metastatic High-risk CSPC

LATITUDE enrolled 1199 patients with newly-diagnosed metastatic, high-risk CSPC who had not received prior cytotoxic chemotherapy. Patients were ineligible if AST and/or ALT ≥2.5 x ULN or if they had liver metastases. All the patients received GnRH analogs or had prior bilateral orchiectomy during the trial. The median duration of treatment with abiraterone acetate and prednisone was 24 months. Table 5 shows adverse reactions on the abiraterone acetate arm that occurred in ≥5% of patients with a ≥2% absolute increase in frequency compared to those on the placebos arm.

Table 5: Adverse Reactions in ≥5% of Patients on the Abiraterone Acetate Arm in LATITUDE1

1 All patients were receiving an GnRH agonist or had undergone orchiectomy.

2 Adverse events graded according to CTCAE version 4.0.

3 Reported as an adverse event or reaction.

4 Including cough, productive cough, upper airway cough syndrome.

Table 6 shows laboratory abnormalities that occurred in >15% of patients, and more frequently (>5%) in the abiraterone acetate arm compared to placebos.

Table 6: Laboratory Abnormalities in >15% of Patients in the Abiraterone Acetate Arm of LATITUDE

Cardiovascular Adverse Reactions

In the combined data of randomized, placebo-controlled clinical studies, cardiac failure occurred more commonly in patients on the abiraterone acetate arm compared to patients on the placebo arm (2.6% versus 0.9%). Grade 3-4 cardiac failure occurred in 1.3% of patients taking abiraterone acetate and led to 5 treatment discontinuations and 4 deaths. Grade 3-4 cardiac failure occurred in 0.2% of patients taking placebo. There were no treatment discontinuations and two deaths due to cardiac failure in the placebo group.

In the same combined data, the majority of arrhythmias were grade 1 or 2. There was one death associated with arrhythmia and three patients with sudden death in the abiraterone acetate arms and five deaths in the placebo arms. There were 7 (0.3%) deaths due to cardiorespiratory arrest in the abiraterone acetate arms and 2 (0.1%) deaths in the placebo arms. Myocardial ischemia or myocardial infarction led to death in 3 patients in the placebo arms and 3 deaths in the abiraterone acetate arms.

6.2 Postmarketing Experience

The following additional adverse reactions have been identified during post approval use of abiraterone acetate with prednisone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Respiratory, Thoracic and Mediastinal Disorders: non-infectious pneumonitis.

Musculoskeletal and Connective Tissue Disorders: myopathy, including rhabdomyolysis.

Hepatobiliary Disorders: fulminant hepatitis, including acute hepatic failure and death.

Cardiac Disorders: QT prolongation and Torsades de Pointes (observed in patients who developed hypokalemia or had underlying cardiovascular conditions).

Immune System Disorders – Hypersensitivity: anaphylactic reactions (severe allergic reactions that include, but are not limited to difficulty swallowing or breathing, swollen face, lips, tongue or throat, or an itchy rash (urticaria)).

7. Drug Interactions

7.1 Drugs that Inhibit or Induce CYP3A4 Enzymes

Based on in vitro data, abiraterone acetate is a substrate of CYP3A4.

In a dedicated drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate dosing frequency .

In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone .

7.2 Effects of Abiraterone on Drug Metabolizing Enzymes

Abiraterone acetate is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. In a CYP2D6 drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine). If alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 substrate drug .

In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate. Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with abiraterone acetate .

8. Use In Specific Populations

8.1 Pregnancy

Risk Summary

The safety and efficacy of abiraterone acetate have not been established in females. Based on findings from animal studies and the mechanism of action, abiraterone acetate can cause fetal harm and potential loss of pregnancy.

There are no human data on the use of abiraterone acetate in pregnant women. In animal reproduction studies, oral administration of abiraterone acetate to pregnant rats during organogenesis caused adverse developmental effects at maternal exposures approximately ≥ 0.03 times the human exposure (AUC) at the recommended dose (see Data).

Data

Animal Data

In an embryo-fetal developmental toxicity study in rats, abiraterone acetate caused developmental toxicity when administered at oral doses of 10, 30 or 100 mg/kg/day throughout the period of organogenesis (gestational days 6-17). Findings included embryo-fetal lethality (increased post implantation loss and resorptions and decreased number of live fetuses), fetal developmental delay (skeletal effects) and urogenital effects (bilateral ureter dilation) at doses ≥10 mg/kg/day, decreased fetal ano-genital distance at ≥30 mg/kg/day, and decreased fetal body weight at 100 mg/kg/day. Doses ≥10 mg/kg/day caused maternal toxicity. The doses tested in rats resulted in systemic exposures (AUC) approximately 0.03, 0.1 and 0.3 times, respectively, the AUC in patients.

8.2 Lactation

Risk Summary

The safety and efficacy of abiraterone acetate have not been established in females. There is no information available on the presence of abiraterone acetate in human milk, or on the effects on the breastfed child or milk production.

8.3 Females and Males of Reproductive Potential

Contraception

Males

Based on findings in animal reproduction studies and its mechanism of action, advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 weeks after the final dose of abiraterone acetate.

Infertility

Based on animal studies, abiraterone acetate may impair reproductive function and fertility in males of reproductive potential .

8.4 Pediatric Use

Safety and effectiveness of abiraterone acetate in pediatric patients have not been established.

8.5 Geriatric Use

Of the total number of patients receiving abiraterone acetate in randomized clinical trials, 70% of patients were 65 years and over and 27% were 75 years and over. No overall differences in safety or effectiveness were observed between these elderly patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

8.6 Patients with Hepatic Impairment

The pharmacokinetics of abiraterone were examined in subjects with baseline mild (N=8) or moderate (N=8) hepatic impairment (Child-Pugh Class A and B, respectively) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of abiraterone after a single oral 1,000 mg dose of abiraterone acetate increased by approximately 1.1-fold and 3.6-fold in subjects with mild and moderate baseline hepatic impairment, respectively compared to subjects with normal hepatic function.

In another trial, the pharmacokinetics of abiraterone were examined in subjects with baseline severe (N=8) hepatic impairment (Child-Pugh Class C) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of abiraterone increased by approximately 7-fold and the fraction of free drug increased 2-fold in subjects with severe baseline hepatic impairment compared to subjects with normal hepatic function.

No dosage adjustment is necessary for patients with baseline mild hepatic impairment. In patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the recommended dose of abiraterone acetate to 250 mg once daily. Do not use abiraterone acetate in patients with baseline severe hepatic impairment (Child-Pugh Class C). If elevations in ALT or AST >5 x ULN or total bilirubin >3 x ULN occur in patients with baseline moderate hepatic impairment, discontinue abiraterone acetate treatment.

For patients who develop hepatotoxicity during treatment, interruption of treatment and dosage adjustment may be required .

8.7 Patients with Renal Impairment

No dosage adjustment is necessary for patients with renal impairment .

10. Overdosage

Human experience of overdose with abiraterone acetate tablets is limited.

There is no specific antidote. In the event of an overdose, stop abiraterone acetate tablets, undertake general supportive measures, including monitoring for arrhythmias and cardiac failure and assess liver function.

11. Abiraterone Acetate Description

Abiraterone acetate, the active ingredient of abiraterone acetate tablets, USP is the acetyl ester of abiraterone. Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each abiraterone acetate tablet, USP contains 250 mg of abiraterone acetate. Abiraterone acetate is designated chemically as (3β)-17-(3-pyridinyl) androsta-5,16-dien-3-yl acetate and its structure is:

Abiraterone acetate is a white to off-white, non-hygroscopic, crystalline powder. Its molecular formula is C26H33NO2 and it has a molecular weight of 391.55. Abiraterone acetate is a lipophilic compound with an octanol-water partition coefficient of 5.12 (Log P) and is practically insoluble in water. The pKa of the aromatic nitrogen is 5.19.

Abiraterone acetate tablets, USP are available in 250 mg uncoated tablets with the following inactive ingredients:

• 250 mg uncoated tablets: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulfate and sodium starch glycolate (derived from potato).

12. Abiraterone Acetate – Clinical Pharmacology

12.1 Mechanism of Action

Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis.

CYP17 catalyzes two sequential reactions: 1) the conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives by 17α-hydroxylase activity and 2) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17, 20-lyase activity. DHEA and androstenedione are androgens and are precursors of testosterone. Inhibition of CYP17 by abiraterone can also result in increased mineralocorticoid production by the adrenals.

Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor.

Abiraterone acetate decreased serum testosterone and other androgens in patients in the placebo-controlled clinical trial. It is not necessary to monitor the effect of abiraterone acetate on serum testosterone levels.

Changes in serum prostate specific antigen (PSA) levels may be observed but have not been shown to correlate with clinical benefit in individual patients.

12.2 Pharmacodynamics

Cardiac Electrophysiology

In a multi-center, open-label, single-arm trial, 33 patients with metastatic CRPC received abiraterone acetate orally at a dose of 1,000 mg once daily at least 1 hour before or 2 hours after a meal in combination with prednisone 5 mg orally twice daily. Assessments up to Cycle 2 Day 2 showed no large changes in the QTc interval (i.e., >20 ms) from baseline. However, small increases in the QTc interval (i.e., <10 ms) due to abiraterone acetate cannot be excluded due to study design limitations.

12.3 Pharmacokinetics

Following administration of abiraterone acetate, the pharmacokinetics of abiraterone have been studied in healthy subjects and in patients with metastatic CRPC. In vivo, abiraterone acetate is converted to abiraterone. In clinical studies, abiraterone acetate plasma concentrations were below detectable levels (<0.2 ng/mL) in >99% of the analyzed samples.

Absorption

Following oral administration of abiraterone acetate to patients with metastatic CRPC, the median time to reach maximum plasma abiraterone concentrations is 2 hours. Abiraterone accumulation is observed at steady-state, with a 2-fold higher exposure (steady-state AUC) compared to a single 1,000 mg dose of abiraterone acetate.

At the dose of 1,000 mg daily in patients with metastatic CRPC, steady-state values (mean ± SD) of Cmax were 226 ± 178 ng/mL and of AUC were 993 ± 639 ng.hr/mL. No major deviation from dose proportionality was observed in the dose range of 250 mg to 1,000 mg. However, the exposure was not significantly increased when the dose was doubled from 1,000 to 2,000 mg (8% increase in the mean AUC).

Effect of Food

Systemic exposure of abiraterone is increased when abiraterone acetate is administered with food. In healthy subjects abiraterone Cmax and AUC0-∞ were approximately 7- and 5-fold higher, respectively, when a single dose of abiraterone acetate was administered with a low-fat meal (7% fat, 300 calories) and approximately 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a high-fat (57% fat, 825 calories) meal compared to overnight fasting. Abiraterone AUC0-∞ was approximately 7-fold or 1.6-fold higher, respectively, when a single dose of abiraterone acetate was administered 2 hours after or 1 hour before a medium fat meal (25% fat, 491 calories) compared to overnight fasting.

Systemic exposures of abiraterone in patients with metastatic CRPC, after repeated dosing of abiraterone acetate were similar when abiraterone acetate was taken with low-fat meals for 7 days and increased approximately 2-fold when taken with high-fat meals for 7 days compared to when taken at least 2 hours after a meal and at least 1 hour before a meal for 7 days.

Given the normal variation in the content and composition of meals, taking abiraterone acetate with meals has the potential to result in increased and highly variable exposures.

Distribution

Abiraterone is highly bound (>99%) to the human plasma proteins, albumin and alpha-1 acid glycoprotein. The apparent steady-state volume of distribution (mean ± SD) is 19,669 ± 13,358 L.

Elimination

In patients with metastatic CRPC, the mean terminal half-life of abiraterone in plasma (mean ± SD) is 12 ± 5 hours.

Metabolism

Following oral administration of 14C-abiraterone acetate as capsules, abiraterone acetate is hydrolyzed to abiraterone (active metabolite). The conversion is likely through esterase activity (the esterases have not been identified) and is not CYP mediated. The two main circulating metabolites of abiraterone in human plasma are abiraterone sulphate (inactive) and N-oxide abiraterone sulphate (inactive), which account for about 43% of exposure each. CYP3A4 and SULT2A1 are the enzymes involved in the formation of N-oxide abiraterone sulphate and SULT2A1 is involved in the formation of abiraterone sulphate.

Excretion

Following oral administration of 14C-abiraterone acetate, approximately 88% of the radioactive dose is recovered in feces and approximately 5% in urine. The major compounds present in feces are unchanged abiraterone acetate and abiraterone (approximately 55% and 22% of the administered dose, respectively).

Specific Populations

Patients with Hepatic Impairment

The pharmacokinetics of abiraterone was examined in subjects with baseline mild (N=8) or moderate (N=8) hepatic impairment (Child-Pugh Class A and B, respectively) and in 8 healthy control subjects with normal hepatic function. Systemic exposure to abiraterone after a single oral 1,000 mg dose given under fasting conditions increased approximately 1.1-fold and 3.6-fold in subjects with mild and moderate baseline hepatic impairment, respectively. The mean half-life of abiraterone is prolonged to approximately 18 hours in subjects with mild hepatic impairment and to approximately 19 hours in subjects with moderate hepatic impairment.

In another trial, the pharmacokinetics of abiraterone were examined in subjects with baseline severe (N=8) hepatic impairment (Child-Pugh Class C) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of abiraterone increased by approximately 7-fold in subjects with severe baseline hepatic impairment compared to subjects with normal hepatic function. In addition, the mean protein binding was found to be lower in the severe hepatic impairment group compared to the normal hepatic function group, which resulted in a two-fold increase in the fraction of free drug in patients with severe hepatic impairment.

Patients with Renal Impairment

The pharmacokinetics of abiraterone were examined in patients with end-stage renal disease (ESRD) on a stable hemodialysis schedule (N=8) and in matched control subjects with normal renal function (N=8). In the ESRD cohort of the trial, a single 1,000 mg abiraterone acetate dose was given under fasting conditions 1 hour after dialysis, and samples for pharmacokinetic analysis were collected up to 96 hours post dose. Systemic exposure to abiraterone after a single oral 1,000 mg dose did not increase in subjects with end-stage renal disease on dialysis, compared to subjects with normal renal function.

Drug Interaction Studies

Clinical Studies

Effect of Other Drugs on Abiraterone Acetate Tablets

Strong CYP3A4 inducers: In a clinical pharmacokinetic interaction study of healthy subjects pretreated with a strong CYP3A4 inducer (rifampin, 600 mg daily for 6 days) followed by a single dose of abiraterone acetate 1,000 mg, the mean plasma AUC∞ of abiraterone was decreased by 55%.

Strong CYP3A4 inhibitors: Co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.

Effect of Abiraterone Acetate Tablets on Other Drugs

CYP2D6 substrates: The Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8-and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily (plus prednisone 5 mg twice daily). The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.

CYP1A2 substrates: When abiraterone acetate 1,000 mg daily (plus prednisone 5 mg twice daily) was given with a single dose of 100 mg theophylline (CYP1A2 substrate), no increase in systemic exposure of theophylline was observed.

CYP2C8 substrates: The AUC of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given to healthy subjects with a single dose of 1,000 mg abiraterone acetate.

In Vitro Studies

Cytochrome P450 (CYP) Enzymes: Abiraterone is a substrate of CYP3A4 and has the potential to inhibit CYP1A2, CYP2D6, CYP2C8 and to a lesser extent CYP2C9, CYP2C19 and CYP3A4/5.

Transporter Systems: In vitro studies show that at clinically relevant concentrations, abiraterone acetate and abiraterone are not substrates of P-glycoprotein (P-gp) and that abiraterone acetate is an inhibitor of P-gp. In vitro, abiraterone and its major metabolites were shown to inhibit the hepatic uptake transporter OATP1B1. There are no clinical data available to confirm transporter based interaction.

13. Nonclinical Toxicology

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

A two-year carcinogenicity study was conducted in rats at oral abiraterone acetate doses of 5, 15, and 50 mg/kg/day for males and 15, 50, and 150 mg/kg/day for females. Abiraterone acetate increased the combined incidence of interstitial cell adenomas and carcinomas in the testes at all dose levels tested. This finding is considered to be related to the pharmacological activity of abiraterone. Rats are regarded as more sensitive than humans to developing interstitial cell tumors in the testes. Abiraterone acetate was not carcinogenic in female rats at exposure levels up to 0.8 times the human clinical exposure based on AUC. Abiraterone acetate was not carcinogenic in a 6-month study in the transgenic (Tg.rasH2) mouse.

Abiraterone acetate and abiraterone was not mutagenic in an in vitro microbial mutagenesis (Ames) assay or clastogenic in an in vitro cytogenetic assay using primary human lymphocytes or an in vivo rat micronucleus assay.

In repeat-dose toxicity studies in male rats (13- and 26-weeks) and monkeys (39-weeks), atrophy, aspermia/hypospermia, and hyperplasia in the reproductive system were observed at ≥50 mg/kg/day in rats and ≥250 mg/kg/day in monkeys and were consistent with the antiandrogenic pharmacological activity of abiraterone. These effects were observed in rats at systemic exposures similar to humans and in monkeys at exposures approximately 0.6 times the AUC in humans.

In a fertility study in male rats, reduced organ weights of the reproductive system, sperm counts, sperm motility, altered sperm morphology and decreased fertility were observed in animals dosed for 4 weeks at ≥30 mg/kg/day orally. Mating of untreated females with males that received 30 mg/kg/day oral abiraterone acetate resulted in a reduced number of corpora lutea, implantations and live embryos and an increased incidence of pre-implantation loss. Effects on male rats were reversible after 16 weeks from the last abiraterone acetate administration.

In a fertility study in female rats, animals dosed orally for 2 weeks until day 7 of pregnancy at ≥30 mg/kg/day had an increased incidence of irregular or extended estrous cycles and pre-implantation loss (300 mg/kg/day). There were no differences in mating, fertility, and litter parameters in female rats that received abiraterone acetate. Effects on female rats were reversible after 4 weeks from the last abiraterone acetate administration.

The dose of 30 mg/kg/day in rats is approximately 0.3 times the recommended dose of 1,000 mg/day based on body surface area.

In 13- and 26-week studies in rats and 13- and 39-week studies in monkeys, a reduction in circulating testosterone levels occurred with abiraterone acetate at approximately one half the human clinical exposure based on AUC. As a result, decreases in organ weights and toxicities were observed in the male and female reproductive system, adrenal glands, liver, pituitary (rats only), and male mammary glands. The changes in the reproductive organs are consistent with the antiandrogenic pharmacological activity of abiraterone acetate.

13.2 Animal Toxicology and/or Pharmacology

A dose-dependent increase in cataracts was observed in rats after daily oral abiraterone acetate administration for 26 weeks starting at ≥50 mg/kg/day (similar to the human clinical exposure based on AUC). In a 39-week monkey study with daily oral abiraterone acetate administration, no cataracts were observed at higher doses (2 times greater than the clinical exposure based on AUC).

14. Clinical Studies

The efficacy and safety of abiraterone acetate with prednisone was established in three randomized placebo-controlled international clinical studies. All patients in these studies received a GnRH analog or had prior bilateral orchiectomy. Patients with prior ketoconazole treatment for prostate cancer and a history of adrenal gland or pituitary disorders were excluded from these trials. Concurrent use of spironolactone was not allowed during the study period.

COU-AA-301: Patients with metastatic CRPC who had received prior docetaxel chemotherapy

In COU-AA-301 (NCT00638690), a total of 1195 patients were randomized 2:1 to receive either abiraterone acetate orally at a dose of 1,000 mg once daily in combination with prednisone 5 mg orally twice daily (N=797) or placebo once daily plus prednisone 5 mg orally twice daily (N=398). Patients randomized to either arm were to continue treatment until disease progression (defined as a 25% increase in PSA over the patient’s baseline/nadir together with protocol-defined radiographic progression and symptomatic or clinical progression), initiation of new treatment, unacceptable toxicity or withdrawal.

The following patient demographics and baseline disease characteristics were balanced between the treatment arms. The median age was 69 years (range 39–95) and the racial distribution was 93% Caucasian, 3.6% Black, 1.7% Asian, and 1.6% Other. Eighty-nine percent of patients enrolled had an ECOG performance status score of 0–1 and 45% had a Brief Pain Inventory-Short Form score of ≥4 (patient’s reported worst pain over the previous 24 hours). Ninety percent of patients had metastases in bone and 30% had visceral involvement. Seventy percent of patients had radiographic evidence of disease progression and 30% had PSA-only progression. Seventy percent of patients had previously received one cytotoxic chemotherapy regimen and 30% received two regimens.

The protocol pre-specified interim analysis was conducted after 552 deaths and showed a statistically significant improvement in overall survival (OS) in patients treated with abiraterone acetate with prednisone compared to patients in the placebo with prednisone arm (Table 9 and Figure 1). An updated survival analysis was conducted when 775 deaths (97% of the planned number of deaths for final analysis) were observed. Results from this analysis were consistent with those from the interim analysis (Table 7).

Table 7: Overall Survival of Patients Treated with Either Abiraterone Acetate or Placebo in Combination with Prednisone in COU-AA-301 (Intent-to-Treat Analysis)

1 p-value is derived from a log-rank test stratified by ECOG performance status score (0-1 vs. 2), pain score (absent vs. present), number of prior chemotherapy regimens (1 vs. 2), and type of disease progression (PSA only vs. radiographic).

2 Hazard Ratio is derived from a stratified proportional hazards model. Hazard ratio <1 favors abiraterone acetate with prednisone.

Figure 1: Kaplan-Meier Overall Survival Curves in COU-AA-301 (Intent-to-Treat Analysis)

COU-AA-302: Patients with metastatic CRPC who had not received prior cytotoxic chemotherapy

In COU-AA-302, (NCT00887198), 1088 patients were randomized 1:1 to receive either abiraterone acetate orally at a dose of 1,000 mg once daily (N=546) or Placebo orally once daily (N=542). Both arms were given concomitant prednisone 5 mg twice daily. Patients continued treatment until radiographic or clinical (cytotoxic chemotherapy, radiation or surgical treatment for cancer, pain requiring chronic opioids, or ECOG performance status decline to 3 or more) disease progression, unacceptable toxicity or withdrawal. Patients with moderate or severe pain, opiate use for cancer pain, or visceral organ metastases were excluded.

Patient demographics were balanced between the treatment arms. The median age was 70 years. The racial distribution of patients treated with abiraterone acetate was 95% Caucasian, 2.8% Black, 0.7% Asian and 1.1% Other. The ECOG performance status was 0 for 76% of patients, and 1 for 24% of patients. Co-primary efficacy endpoints were overall survival and radiographic progression-free survival (rPFS). Baseline pain assessment was 0–1 (asymptomatic) in 66% of patients and 2–3 (mildly symptomatic) in 26% of patients as defined by the Brief Pain Inventory-Short Form (worst pain over the last 24 hours).

Radiographic progression-free survival was assessed with the use of sequential imaging studies and was defined by bone scan identification of 2 or more new bone lesions with confirmation (Prostate Cancer Working Group 2 criteria) and/or modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria for progression of soft tissue lesions. Analysis of rPFS utilized centrally-reviewed radiographic assessment of progression.

The planned final analysis for OS, conducted after 741 deaths (median follow up of 49 months) demonstrated a statistically significant OS improvement in patients treated with abiraterone acetate with prednisone compared to those treated with placebo with prednisone (Table 8 and Figure 2). Sixty-five percent of patients on the abiraterone acetate arm and 78% of patients on the placebo arm used subsequent therapies that may prolong OS in metastatic CRPC. Abiraterone acetate was used as a subsequent therapy in 13% of patients on the abiraterone acetate arm and 44% of patients on the placebo arm.

Table 8: Overall Survival of Patients Treated with Either Abiraterone Acetate or Placebo in Combination with Prednisone in COU-AA-302 (Intent-to-Treat Analysis)

Figure 2: Kaplan Meier Overall Survival Curves in COU-AA-302

At the pre-specified rPFS analysis, 150 (28%) patients treated with abiraterone acetate with prednisone and 251 (46%) patients treated with placebo with prednisone had radiographic progression. A significant difference in rPFS between treatment groups was observed (Table 9 and Figure 3).

Table 9: Radiographic Progression-free Survival of Patients Treated with Either Abiraterone Acetate or Placebo in Combination with Prednisone in COU-AA-302 (Intent-to-Treat Analysis)

Figure 3: Kaplan Meier Curves of Radiographic Progression-free Survival in COU-AA-302 (Intent-to-Treat Analysis)

The primary efficacy analyses are supported by the following prospectively defined endpoints. The median time to initiation of cytotoxic chemotherapy was 25.2 months for patients in the abiraterone acetate arm and 16.8 months for patients in the placebo arm (HR=0.580; 95% CI: [0.487, 0.691], p < 0.0001).

The median time to opiate use for prostate cancer pain was not reached for patients receiving abiraterone acetate and was 23.7 months for patients receiving placebo (HR=0.686; 95% CI: [0.566, 0.833], p=0.0001). The time to opiate use result was supported by a delay in patient reported pain progression favoring the abiraterone acetate arm.

LATITUDE: Patients with metastatic high-risk CSPC

In LATITUDE (NCT01715285), 1199 patients with metastatic high-risk CSPC were randomized 1:1 to receive either abiraterone acetate orally at a dose of 1,000 mg once daily with prednisone 5 mg once daily (N=597) or placebos orally once daily (N=602). High-risk disease was defined as having at least two of three risk factors at baseline: a total Gleason score of ≥8, presence of ≥3 lesions on bone scan, and evidence of measurable visceral metastases. Patients with significant cardiac, adrenal, or hepatic dysfunction were excluded. Patients continued treatment until radiographic or clinical disease progression, unacceptable toxicity, withdrawal or death. Clinical progression was defined as the need for cytotoxic chemotherapy, radiation or surgical treatment for cancer, pain requiring chronic opioids, or ECOG performance status decline to ≥3.

Patient demographics were balanced between the treatment arms. The median age was 67 years among all randomized subjects. The racial distribution of patients treated with abiraterone acetate was 69% Caucasian, 2.5% Black, 21% Asian, and 8.1% Other. The ECOG performance status was 0 for 55%, 1 for 42%, and 2 for 3.5% of patients. Baseline pain assessment was 0-1 (asymptomatic) in 50% of patients, 2-3 (mildly symptomatic) in 23% of patients, and ≥4 in 28% of patients as defined by the Brief Pain Inventory-Short Form (worst pain over the last 24 hours).

A major efficacy outcome was overall survival. The pre-specified interim analysis after 406 deaths showed a statistically significant improvement in OS in patients on abiraterone acetate with prednisone compared to those on placebos. Twenty-one percent of patients on the abiraterone acetate arm and 41% of patients on the placebos arm received subsequent therapies that may prolong OS in metastatic CRPC. An updated survival analysis was conducted when 618 deaths were observed. The median follow-up time was 52 months. Results from this analysis were consistent with those from the pre-specified interim analysis (Table 10 and Figure 4). At the updated analysis, 29% of patients on the abiraterone acetate arm and 45% of patients on the placebos arm received subsequent therapies that may prolong OS in metastatic CRPC.

Table 10: Overall Survival of Patients Treated with Either Abiraterone Acetate or Placebos in LATITUDE (Intent-to-Treat Analysis)

NE=Not estimable

1 This is based on the pre-specified interim analysis

2 p value is from log-rank test stratified by ECOG PS score (0/1 or 2) and visceral (absent or present).

3 Hazard Ratio is derived from a stratified proportional hazards model. Hazard ratio <1 favors abiraterone acetate with prednisone.

Figure 4: Kaplan-Meier Plot of Overall Survival; Intent-to-treat Population in LATITUDE Updated Analysis

The major efficacy outcome was supported by a statistically significant delay in time to initiation of chemotherapy for patients in the abiraterone acetate arm compared to those in the placebos arm. The median time to initiation of chemotherapy was not reached for patients on abiraterone acetate with prednisone and was 38.9 months for patients on placebos (HR = 0.44; 95% CI: [0.35, 0.56], p < 0.0001).

16. How is Abiraterone Acetate supplied

Abiraterone Acetate Tablets, USP 250 mg – Uncoated tablets

Abiraterone acetate tablets, USP are available as white to off-white, oval tablets debossed with “WW597” on one side.

NDC 82249-010-12 120 tablets available in high-density polyethylene bottles

Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted in the range from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Keep out of reach of children.

Based on its mechanism of action, abiraterone acetate tablets may harm a developing fetus. Women who are pregnant or women who may be pregnant should not handle abiraterone acetate 250 mg uncoated tablets or other abiraterone acetate tablets if broken, crushed, or damaged without protection, e.g., gloves .

Infertility•Advise male patients that abiraterone acetate tablets may impair fertility

Distributed by:
CivicaScript, LLC
Lehi, Utah 84043

Manufactured by:
Arab Pharmaceuticals Manufacturing PSC

PO Box 41

Sahab – Jordan

2INABI250TC-E
Revised: November 2023

PATIENT INFORMATION

Abiraterone Acetate Tablets, USP
[a” bir a’ ter one as’ e tate]

What are abiraterone acetate tablets?

Abiraterone acetate tablets are a prescription medicine that are used along with prednisone. Abiraterone acetate tablets are used to treat men with prostate cancer that has spread to other parts of the body.

It is not known if abiraterone acetate tablets are safe and effective in females or children.

Before taking abiraterone acetate tablets, tell your healthcare provider about all of your medical conditions, including if you:•have heart problems•have liver problems•have diabetes•have a history of adrenal problems•have a history of pituitary problems•are receiving any other treatment for prostate cancer•are pregnant or plan to become pregnant. Abiraterone acetate tablets can cause harm to your unborn baby and loss of pregnancy (miscarriage). Females who are or may become pregnant should not handle abiraterone acetate uncoated tablets or other abiraterone acetate tablets if broken, crushed, or damaged without protection, such as gloves.•have a partner who is pregnant or may become pregnant.oMales who have female partners who are able to become pregnant should use effective birth control (contraception) during treatment with abiraterone acetate tablets and for 3 weeks after the last dose of abiraterone acetate tablets.•are breastfeeding or plan to breastfeed. It is not known if abiraterone acetate passes into your breastmilk.

Tell your healthcare provider about all the medicines you take or treatments you receive, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Abiraterone acetate tablets can interact with many other medicines.

You should not start or stop any medicine before you talk with the healthcare provider that prescribed abiraterone acetate tablets.

Know the medicines you take. Keep a list of them with you to show to your healthcare provider and pharmacist when you get a new medicine.

How should I take abiraterone acetate tablets?•Take abiraterone acetate tablets and prednisone exactly as your healthcare provider tells you.•Take your prescribed dose of abiraterone acetate tablets 1 time a day.•Your healthcare provider may change your dose if needed.•Do not change or stop taking your prescribed dose of abiraterone acetate tablets or prednisone without talking with your healthcare provider first.•Take abiraterone acetate tablets as a single dose one time a day on an empty stomach. Do not eat food 2 hours before and 1 hour after taking abiraterone acetate.•Do not take abiraterone acetate with food. Taking abiraterone acetate with food may cause more of the medicine to be absorbed by the body than is needed and this may cause side effects.•Swallow abiraterone acetate tablets whole. Do not crush or chew tablets.•Take abiraterone acetate tablets with water.•If you miss a dose of abiraterone acetate tablets or prednisone, take your prescribed dose the following day. If you miss more than 1 dose, tell your healthcare provider right away.•Your healthcare provider will do blood tests to check for side effects.

What are the possible side effects of abiraterone acetate tablets?

Abiraterone acetate tablets may cause serious side effects including:•High blood pressure (hypertension), low blood potassium levels (hypokalemia), fluid retention (edema), and irregular heartbeats can happen during treatment with abiraterone acetate tablets. This can be life threatening. To decrease the chance of this happening, you must take prednisone with abiraterone acetate tablets exactly as your healthcare provider tells you. Your healthcare provider will check your blood pressure, do blood tests to check your potassium levels, and check for any signs and symptoms of fluid retention every month during treatment with abiraterone acetate tablets.

Tell your healthcare provider if you get any of the following symptoms:

•Adrenal problems may happen if you stop taking prednisone, get an infection, or are under stress.•Severe liver problems. You may develop changes in liver function blood tests. Your healthcare provider will do blood tests to check your liver before treatment with abiraterone acetate tablets and during treatment with abiraterone acetate tablets. Liver failure may occur, which can lead to death. Tell your healthcare provider right away if you notice any of the following changes:oyellowing of the skin or eyesodarkening of the urineosevere nausea or vomiting•Increased risk of bone fracture and death when abiraterone acetate tablets and prednisone or prednisolone, is used in combination with a type of radiation called radium Ra 223 dichloride. Tell your healthcare provider about any other treatments you are taking for prostate cancer.•Severe low blood sugar (hypoglycemia). Severe low blood sugar with abiraterone acetate tablets can happen in people who have diabetes and take certain antidiabetic medicines. You and your healthcare provider should check your blood sugar levels regularly during treatment with abiraterone acetate tablets and after you stop treatment. Your healthcare provider may also need to change the dose of your antidiabetic medicines. Signs and symptoms of low blood sugar may include:

The most common side effects of abiraterone acetate tablets include:

Abiraterone acetate tablets may cause fertility problems in males, which may affect the ability to father children. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of abiraterone acetate tablets. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store abiraterone acetate tablets?•Store abiraterone acetate tablets at room temperature between 68oF to 77oF (20oC to 25oC).

Keep abiraterone acetate tablets and all medicines out of the reach of children.

General information about the safe and effective use of abiraterone acetate tablets.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use abiraterone acetate tablets for a condition for which it was not prescribed. Do not give abiraterone acetate tablets to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your healthcare provider or pharmacist for information about abiraterone acetate tablets that is written for health professionals.

What are the ingredients of abiraterone acetate tablets?

Active ingredient: abiraterone acetate

Inactive ingredients: 250 mg uncoated tablets: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulfate and sodium starch glycolate (derived from potato).

This Patient Information has been approved by the U.S. Food and Drug Administration.

Distributed by:
CivicaScript, LLC
Lehi, Utah 84043

Manufactured by:
Arab Pharmaceuticals Manufacturing PSC

PO Box 41
Sahab – Jordan

2INABI250TMC-E
Revised: November 2023

PRINCIPAL DISPLAY PANEL

NDC 82249-010-12

Abiraterone Acetate
Tablets, 250 mg

Rx Only
120 Tablets

What is Abecma?

Abecma is a CAR T cell therapy used to treat relapsed or refractory multiple myeloma to help patients live longer without cancer progressing or passing away. Abecma infusion is made from your white blood cells, which are changed so that they can recognize and kill multiple myeloma cancer cells. It is given as a one-time infusion after the process of making your personal infusion.

Abecma FDA approval was granted on March 26, 2021, for adult patients who have relapsed or refractory multiple myeloma and have tried two or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an antiCD38 monoclonal antibody.  Abecma approval was based on positive results from KarMMa Pivotal Trial that showed 72% idecabtagene vicleucel treated patients had a response that was a partial response (19%), very good partial response (25%), or stringent complete response (28%). 

Abecma mechanism of action (MOA) is as a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell immunotherapy.

How does Abecma work?

Abecma (idecabtagene vicleucel) is a medicine made from your own white blood cells, which are genetically modified so that they can recognize and attack your multiple myeloma cells. Abecma Car T therapy works as your T cells (a type of white blood cell) are changed to recognize proteins on the outside MM cancer cells so that they can attack the cancer cells. A more detailed explanation of how it works is:

• Your T cells are a type of white blood cell that is part of your immune system that can attack foreign substances in your body.
• On the outside of the multiple myeloma cells are proteins called B-cell maturation antigen (BCMA).
• Normally, T cells do not recognize MM cells, so do not attack and kill them.
• Your T cells (type of white blood cell) are collected and sent to the manufacturing center where they add to the T cell a special receptor called CAR (chimeric antigen receptor) that is designed to bind to certain proteins in cancer cells.
• Your T Cells will now be able to recognize the BCMA protein on the MM cells and kill the cancer cells.
• These changed T cells, called chimeric antigen receptor T cells (CAR T cells), are then grown in large numbers in the laboratory and then given as a one-time Abecma infusion to the MM cancer patient.

BCMA = B-cell maturation antigen. CAR-T = chimeric antigen receptor-T cell.

How will I receive Abecma?

Abecma is made from your own white blood cells, so your blood will be collected by a process called “leukapheresis” (LOO-kuh-feh-REE-sis). This is when they take blood from your bloodstream and separate white blood cells from the rest of your blood, which they return to the bloodstream.

Your white blood cells will be sent to a manufacturing center to make your infusion, which usually takes about 4 weeks, but the time may vary.

Before you have your infusion, you will be given chemotherapy for 3 days to prepare your body.

You are usually given Abecma 2 days after completion of chemotherapy.

Abecma is given as an intravenous infusion through a catheter (tube) placed into your vein. Your dose may be given in one or more infusion bags. The infusion usually takes up to 30 minutes for each infusion bag.

Approximately 30 to 60 minutes before your infusion, you will be given an antihistamine and acetaminophen.

You will be monitored at the certified healthcare facility, where you will receive your treatment daily for at least 7 days after the infusion.

You should plan to stay within 2 hours of this location for at least 4 weeks after getting Abecma. Your healthcare provider will check to see that your treatment is working and help you with any side effects that may occur.

Your infusion may be delayed up to 7 days if you have any of the following conditions:

• unresolved serious adverse events (especially pulmonary events, cardiac events, or hypotension), including those after preceding chemotherapies,
• active infections, or inflammatory disorders.

Abecma side effects

Common Abecma side effects may include:

• cytokine release syndrome (confusion, trouble breathing, fast or irregular heartbeats, feeling light-headed or very tired);
• headache, dizziness;
• problems with speech;
• low blood cell counts;
• fever, chills, tiredness, or other signs of infection;
• decreased appetite, severe nausea or diarrhea;
• pain in your bones, joints, or muscles;
• swelling anywhere in your body; or
• cold symptoms such as stuffy nose, sneezing, sore throat, cough.

Serious Abecma side effects:

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

A serious side effect of this medicine is called cytokine release syndrome (CRS). Tell your caregivers right away if you have signs of this condition: fever, chills, trouble breathing, severe vomiting or diarrhea, tremors, shaking, fast or irregular heartbeats, feeling light-headed, or feeling very tired. Your caregivers will have medication available to quickly treat CRS if it occurs.

Also, tell your caregivers or seek emergency medical attention if you have signs of nerve problems, blood disorders, or infection. Symptoms may include problems with speech, problems with thinking or memory, confusion, fatigue, fever, swelling, or a seizure.

Call your doctor at once if you have:

• headaches, dizziness, drowsiness;
• problems with thinking or memory;
• trouble speaking or understanding what is said to you;
• tremors, anxiety, sleep problems;
• seizure;
• right-sided upper stomach pain, vomiting, loss of appetite, yellowing of your skin or eyes, and not feeling well; or
• low blood cell counts – fever, chills, tiredness, flu-like symptoms, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath.

Warnings

Abecma can cause a very common side effect called cytokine release syndrome or CRS, which can be severe or fatal. Symptoms of CRS include fever, difficulty breathing, dizziness or light-headedness, nausea, headache, fast heartbeat, low blood pressure, or fatigue. Tell your healthcare provider right away if you develop fever or any of these other symptoms.

Abecma can increase the risk of life-threatening infections that may lead to death. Tell your healthcare provider right away if you develop fever, chills, or any signs or symptoms of an infection. It may also lower one or more types of blood cells (red blood cells, white blood cells, or platelets), which may make you feel weak or tired or increase your risk of severe infection or bleeding. After treatment, your healthcare provider will test your
blood to check for this. Tell your healthcare provider right away if you get a fever, are feeling tired, or have bruising or bleeding.

Abecma may increase your risk of getting cancer including certain types of blood cancers, called T-cell malignancies. Your healthcare provider should monitor you for these.

Abecma may also cause life-threatening nerve problems, blood disorders, or other life-threatening reactions. Tell your caregivers or seek emergency medical attention if you have problems with speech, problems with thinking or memory, confusion, seizures, fatigue, shortness of breath, or chest pain.

Having Abecma in your blood may cause a false-positive human immunodeficiency virus (HIV) test result by some commercial tests.

It is important that you tell your healthcare providers that you have received Abecma and to show them your Patient Wallet Card. Your healthcare provider may give you other medicines to treat your side effects.

Before taking this medicine

Tell your doctor if you have ever had:

• an active infection or inflammation;
• hepatitis B;
• cytomegalovirus; or
• if you have received a vaccine in the past 6 weeks.

Pregnancy

This medicine is not recommended for women who are pregnant, and pregnancy after Abecma infusion should be discussed with the treating physician. Women may need to take a pregnancy test before receiving this medicine. You may also need to use birth control to prevent pregnancy during and shortly after treatment with Abecma and chemotherapy.

Assess immunoglobulin levels in newborns of mothers treated with this infusion. If you receive the infusion during pregnancy, your baby’s blood may need to be tested after it is born. This is to evaluate any effects the medicine may have had on the baby.

Breastfeeding

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risks.

Abecma pregnancy and breastfeeding warnings (more detail)

What should I avoid while using Abecma?

Abecma can cause weakness, drowsiness, confusion, problems with memory or coordination, and seizures. Avoid driving or operating machinery for at least 8 weeks after you are have your infusion.

Vaccination with live virus vaccines is not recommended for at least 6 weeks before the start of lymphodepleting chemotherapy, during Abecma treatment, and until immune recovery following your infusion.

Do not donate blood, an organ, or any tissues or cells.

Abecma REMS

Abecma is only available through a restricted program called the Abecma REMS (Risk Evaluation and Mitigation Strategy) program designed to manage the risk of serious side effects. The Abecma REMS program aims to reduce  the risks of cytokine release syndrome (CRS) and neurologic toxicities. This infusion can only be administered at a REMS-certified healthcare facility that is specially certified and has on-site, immediate access to treatments (tocilizumab) and facilities that may be required.

What other drugs will affect Abecma?

Other drugs may interact with Abecma, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Abecma drug interactions (more detail)

Does Abecma interact with my other drugs?

Enter medications to view a detailed interaction report using our Drug Interaction Checker.Drug nameAdd a drug to check interactionsAdd

Storage

• Store Abecma frozen in the vapor phase of liquid nitrogen (less than or equal to minus 130°C).
• Thaw Abecma prior to the infusion, according to the Prescribing Information.

Ingredients

Abecma is supplied in one or more infusion bag(s) containing a frozen suspension of genetically modified autologous T cells in 5% DMSO.

Abecma is made specifically for each individual patient with their own white blood cells. Match the identity of the patient with the patient identifiers on the cassette(s) and infusion bag(s) upon receipt.