What is oral cyanocobalamin?

Cyanocobalamin, also known as Vitamin B12, is a form of vitamin B found in foods. Vitamin B12 is important for growth, cell reproduction and energy, healthy red blood cell formation and to keep your nerve cells healthy.

Cyanocobalamin is likely effective in alternative medicine as an aid in treating or preventing low levels of vitamin B12 in your body. Low levels of Vitamin B12 can be caused by an autoimmune disease, pernicious anemia, certain types of surgery, stomach disorders, or malnutrition.

Cyanocobalamin has been used in alternative medicine as a possibly effective aid in treating canker sores, and may help lower homocysteine levels in blood (a risk factor for heart disease).

Cyanocobalamin has also been used to treat memory and thinking problems, Alzheimer’s disease, reduce falls, help with bone health, cataracts, and sleep disorders. However, research has shown that cyanocobalamin may not be effective in treating these conditions.

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

Oral cyanocobalamin 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.

Less serious side effects may be more likely, and you may have none at all.

This is not a complete list of side effects and others may occur.

Warnings

Follow all directions on the product label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Before taking this medicine

You should not use cyanocobalamin if you are allergic to vitamin B12, cobalamin, or cobalt.

Ask a doctor, pharmacist, or other healthcare provider if it is safe for you to use this product if you have ever had:

• any condition that makes it hard for your body to absorb nutrients from food (malabsorption);
• cancer; or
• if you use a blood thinner (such as warfarin).

Ask a doctor before using cyanocobalamin if you are pregnant or breastfeeding.

Do not give cyanocobalamin to a child without medical advice.

How should I use oral cyanocobalamin?

When considering the use of cyanocobalamin, seek the advice of your doctor. You may also consider consulting a practitioner who is trained in the use of herbal/health supplements.

If you choose to use cyanocobalamin, use it as directed on the package or as directed by your doctor, pharmacist, or other healthcare provider. Do not use more of this product than is recommended on the label.

Do not use different forms of cyanocobalamin (pills, liquids, and others) at the same time or you could have an overdose.

Carefully follow instructions about whether to take your cyanocobalamin with or without food.

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

You must chew the chewable tablet thoroughly before you swallow it.

Measure cyanocobalamin liquid with the supplied measuring device (not a kitchen spoon).

Do not swallow a lozenge, disintegrating tablet, or sublingual tablet whole. Allow it to dissolve in your mouth without chewing. sublingual tablet or liquid should be placed under your tongue.

If you need surgery, tell the surgeon ahead of time that you are using cyanocobalamin. You may need to stop using cyanocobalamin for a short time.

Cyanocobalamin can affect the results of certain lab tests. Tell any doctor who treats you that you are using cyanocobalamin.

The recommended daily dose of cyanocobalamin changes with age. Follow your healthcare provider’s instructions. You may also consult the Office of Dietary Supplements of the NIH, or the USDA Nutrient Database of recommended daily allowances for more information.

Call your doctor if the condition you are treating with cyanocobalamin does not improve, or if it gets worse while using this product.

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

Store the cyanocobalamin liquid in the refrigerator after opening for best results.

Cyanocobalamin dosing information

Usual Adult Dose for Pernicious Anemia:

Initial dose: 100 mcg intramuscularly or deep subcutaneous once a day for 6 to 7 days
If clinical improvement and reticulocyte response is seen from the above dosing:
-100 mcg every other day for 7 doses, then:
-100 mcg every 3 to 4 days for 2 to 3 weeks, then:
Maintenance dose: 100 to 1000 mcg monthly
Duration of therapy: Life

Comments:
-Administer concomitant folic acid if needed.
-Chronic treatment should be done with an oral preparation in patients with normal intestinal absorption.

Usual Adult Dose for B12 Nutritional Deficiency:

25 to 2000 mcg orally daily

Usual Adult Dose for Schilling Test:

1000 mcg intramuscularly is the flushing dose

Usual Pediatric Dose for B12 Nutritional Deficiency:

0.5 to 3 mcg daily

What happens if I miss a dose?

Use cyanocobalamin as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not use 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 oral cyanocobalamin?

Avoid drinking large amounts of alcohol. Heavy drinking can make it harder for your body to absorb cyanocobalamin.

What other drugs will affect oral cyanocobalamin?

Do not use cyanocobalamin without medical advice if you are using any of the following medications:

• vitamin C supplements;
• folic acid;
• potassium supplements;
• oral diabetes medicine that contains metformin; or
• medicines that reduce stomach acid, such as cimetidine, omeprazole, lansoprazole, Nexium, Prevacid, Prilosec, Zantac, and others.

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.

Calquence (acalabrutinib) is a targeted cancer treatment used for chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL), in certain patients.

Calquence is a Bruton tyrosine kinase (BTK) inhibitor that works by blocking BTK, a protein that plays a key role in cancer cell growth and division. By inhibiting BTK, Calquence helps to slow the progression of cancer and helps extend patients’ lives

Calquence capsules and tablets are taken twice daily.

Calquence FDA approval was granted on October 31, 2017, for treating MCL. Its approval was later expanded to include CLL and SLL. Calquence is manufactured by AstraZeneca Pharmaceuticals.

How does Calquence work? 

Some cancer cells get signals to grow and divide from a protein called Bruton tyrosine kinase (BTK). The Calquence mechanism of action is by blocking Bruton tyrosine kinase (BTK), which helps to stop cancer cells from growing and multiplying, to help reduce cancer growth. The Calquence class of medications is called BTK inhibitors and is a targeted therapy.

Is Calquence chemotherapy?

No, Calquence is not chemotherapy; it is a targeted therapy, specifically a Bruton’s tyrosine kinase (BTK) inhibitor.

What is Calquence used for?

Calquence is used for adult patients with:

• chronic lymphocytic leukemia (CLL)
• small lymphocytic lymphoma (SLL) 
• mantle cell lymphoma (MCL)  in patients
  • who have received at least one prior therapy, or
  • who are previously untreated, and
    • are ineligible for autologous hematopoietic stem cell transplantation (HSCT), and
    • used in combination with bendamustine and rituximab.

Calquence side effects

Common Calquence side effects

Common Calquence side effects include:

• Infection (65%)
• Upper respiratory tract infection – URTI (35%)
• Lower respiratory tract infection – LRTI (18%)
• Urinary tract infection – UTI (15%)
• Headache (39%)
• Dizziness (20%)
• Diarrhea (35%)
• Nausea (22%)
• Musculoskeletal pain (32%)
• Joint pain (16%)
• Tiredness (23%)
• Bruising (21%)
• Rash (25%)
• Hemorrhage (20%).

There were also changes in blood test levels neutropenia 23% (low white blood cells), anemia 53% (low red blood cells), thrombocytopenia 32% (low platelet levels, and lymphocytosis 16% (high white blood cells).

The above common side effects occurred in patients being treated with Calquence CLL as monotherapy and occurred in 15% or more of patients.

Serious side effects

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

• unusual bleeding – nosebleeds, bleeding gums, abnormal vaginal bleeding, any bleeding that will not stop
• bleeding inside your body – weakness, dizziness, confusion; problems with speech, prolonged headache, bloody or tarry stools, pink or brown urine; coughing up blood or vomit that looks like coffee grounds
• heart rhythm disorders – dizziness, chest pain, shortness of breath, fast or irregular heart rate, or feeling light-headed. Serious cardiac arrhythmias have occurred in patients treated with Calquence
• 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 infection – fever, chills, tiredness, flu-like symptoms, cough with mucus, chest pain, trouble breathing.

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

This medicine may cause a brain infection that can lead to disability or death. Tell your doctor if you have problems with speech, thought, vision, or muscle movement. These symptoms can get worse quickly.

Liver toxicity, which may be severe or fatal, has been reported with Bruton tyrosine kinase inhibitors, including this medicine. Your healthcare provider will monitor your liver function tests before starting treatment with this medicine and while you are taking it. Tell your healthcare provider immediately if you experience abdominal discomfort, dark urine, or yellowing of the skin.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

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

Warnings

Bleeding problems. Calquence can make it easier for you to bleed. Contact your doctor or seek emergency medical attention if you have any bleeding that will not stop.

Call your doctor at once if you have signs of bleeding inside your body, such as: dizziness, weakness, confusion, headache, speech problems, black or bloody stools, pink or brown urine, or coughing up blood or vomit that looks like coffee grounds.

Your healthcare provider may stop this medicine for any planned medical, surgical, or dental procedure

Infections: Monitor for signs and symptoms of infection and treat promptly. 

Change in blood tests. It may cause low levels of red blood cells (anemia), white blood cells (leukopenia), or platelets (thrombocytopenia). You will have complete blood counts regularly.

Second Primary Cancer: Other cancers have occurred, including skin cancers and other solid tumors. Always use sun protection. 

Heart rhythm changes: You will be monitored for symptoms of problems with the rate or rhythm of your heart (arrhythmias).

Severe hepatic impairment. This medicine should be avoided in patients with severe liver impairment and liver problems that have occurred in patients taking this medicine. If you have symptoms of stomach pain, dark-colored urine of dark color, or yellowing of your skin, you should contact your healthcare provider, who will monitor your liver function.

Before taking this medicine

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

• an active or chronic infection, including hepatitis B;
• a heart rhythm disorder;
• bleeding problems;
• recent surgery or plan to have surgery, medical or dental procedure; or
• liver problems

Taking Calquence may increase your risk of developing other cancers. Ask your doctor about this risk.

Pregnancy

Tell your healthcare professional if you are pregnant or plan to become pregnant, as Calquence may harm your unborn baby and problems during childbirth (dystocia). Your healthcare provider may do a pregnancy test before you start treatment, if you are able to become pregnant.

Females who are able to become pregnant should use effective birth control (contraception) during treatment with this medicine and for at least 1 week after the last dose.

Breastfeeding

Tell your healthcare professional if you are breastfeeding or plan to breastfeed. It is not known if Calquence passes into your breast milk. Do not breastfeed during treatment with this medicine and for at least 2 weeks after your final dose.

How should I take Calquence?

Calquence directions

• Calquence tablet and capsules is usually taken twice per day (about 12 hours apart) with or without food, with a glass of water. Swallow the tablet and capsule whole, and do not crush, chew, break, open, or dissolve it.
• If you need to take an antacid medicine, take it either 2 hours before or 2 hours after you take Calquence.  If you need to take certain other medicines called acid reducers (H-2 receptor blockers), take Calquence 2 hours before the acid reducer medicine.
• Your healthcare provider may tell you to decrease your dose, temporarily stop, or completely stop taking this medicine if you develop certain side effects. 
• Take this medicine exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.
• If you need surgery, tell the surgeon beforehand that you are using this medication. You may need to stop using the medicine for a short time.
• While taking this medicine, you may need frequent blood tests.
• If you’ve had hepatitis B, it may come back. You may need liver function tests while using this medicine.

Calquence dosing information

Usual monotherapy adult dose of Calquence for CLL,  SLL, or MCL

Dose: Calquence 100 mg capsule or tablet orally every 12 hours until the cancer progresses or there is unacceptable toxicity.

Usual adult dose in combination with obinutuzumab 

For patients with previously untreated CLL or SLL. The recommended dose of Calquence 100 mg taken orally approximately every 12 hours. Start Calquence at Cycle 1 (each cycle is 28 days). Start obinutuzumab (Gazyva) at Cycle 2 for a total of 6 cycles and refer to the obinutuzumab prescribing information for recommended dosing. 

Administer Calquence prior to obinutuzumab when given on the same day. 

Usual adult Calquence dose in combination with bendamustine and rituximab 

For patients with previously untreated MCL. The recommended dosage of 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity

Start Calquence on Day 1 of Cycle 1 (each cycle is 28 days) 

Administer bendamustine 90 mg/m2 on Days 1 and 2 and rituximab 375 mg/m2 on Day 1 of Cycle 1 and continue for a total of 6 cycles. 

Patients achieving a response (PR or CR) after the first 6 cycles may receive maintenance rituximab on Day 1 of every other cycle for a maximum of 12 additional doses, starting on Cycle 8 up to Cycle 30 

General dose information

How long do you take Calquence? Calquence treatment should be continued until the cancer progresses or there is unacceptable toxicity.

Formulations available: 

• Calquence 100mg capsules.
• Calquence 100mg tablets.

Hepatic Impairment. You should not take this medicine if you have severe hepatic impairment. Dose modifications are not required for patients with mild or moderate hepatic impairment.

Dose modifications for drug interactions. See detailed dosing information for dose modifications required for drug interactions.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if you are more than 3 hours late for the dose. Do not use 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 taking Calquence?

Avoid taking an antacid such as Tums or calcium carbonate within 2 hours before or after you take Calquence.

Calquence 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.

What other drugs will affect Calquence?

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

Drug interactions with groups:

• Strong CYP3A Inhibitors: Avoid co-administration of strong CYP3A Inhibitors with Calquence.
• Moderate CYP3A Inhibitors: Reduce the dosage of Calquence if these medicines are used together.
• Strong CYP3A Inducers: Avoid co-administration of strong CYP3A Inducers with Calquence. If co-administration is unavoidable, then the dosage of Calquence should be increased.

If you use a stomach acid reducer such as cimetidine, ranitidine, Tagamet, Pepcid, or Zantac, take the Calquence dose 2 hours before taking any of these other medicines.

Tell your doctor about all your current medicines. Many drugs can affect acalabrutinib, especially:

• a blood thinner (warfarin, Coumadin, Jantoven);
• an antibiotic or antifungal medicine (itraconazole, fluconazole, erythromycin, rifampin);
• antiviral medicine to treat hepatitis C or HIV/AIDS;
• heart medication (diltiazem) ; or
• a proton pump inhibitor stomach acid medicine – such as omeprazole, lansoprazole, rabeprazole, Nexium, Prevacid, Prilosec, Protonix, and others.

This list is not complete and many other drugs may interact with acalabrutinib. This includes prescription and over-the-counter medicines, vitamins, and herbal products.

Calquence Copay Card and Calquence Cares

The Calquence Copay Card can help you pay as little as $0 per month for out-of-pocket costs if you have commercial insurance plans.

AstraZeneca has a support program called AstraZeneca Access 360, which can help with questions about insurance, costs, affordability options, and other patient resources.

For patients with Medicare or no insurance facing affordability challenges, there is also an AstraZeneca Prescriptions Savings plan called AZ&ME.

Calquence Package Insert 

Review the Calquence Package Insert (PI) for more detailed information about this medicine. The PI contains more comprehensive 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.

Brukinsa is used to treat adults with mantle cell lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma, and follicular lymphoma. It is an oral capsule or tablet that is taken once or twice a day.

Brukinsa (zanubrutinib) was first approved in 2019. There is no generic.

FDA approvals and indications

Brukinsa is a prescription oral capsule or tablet used to treat adults with:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Follicular lymphoma (FL), in combination with obinutuzumab, whose disease has come back or did not respond to treatment (relapsed or refractory) and who have received at least 2 prior treatments
• Mantle cell lymphoma (MCL), who have received at least 1 prior treatment for their cancer.
• Waldenström’s macroglobulinemia (WM)
• Marginal zone lymphoma (MZL), when the disease has come back or did not respond to treatment (relapsed or refractory), and who have received at least one anti-CD20-based regimen.

It is not known if this medicine is safe and effective in children.

How does Brukinsa work?

Brukinsa is a targeted treatment, not a chemotherapy drug, and works by directly blocking an enzyme, called Bruton’s tyrosine kinase (BTK), preventing its activity.

• BTK is a signaling molecule for pathways that cause an increase in B cells, a type of white blood cell that makes infection-fighting antibodies.
• Inhibition of BTK reduces the growth and spread of malignant B cells.

Brukinsa belongs to the drug class called BTK inhibitors.

Side effects

The most common side effects of Brukinsa are:

• diarrhea or constipation
• low platelet or other blood cell counts
• easy bruising or bleeding
• musculoskeletal pain
• high blood pressure
• a rash
• cold or flu symptoms, such as stuffy nose, sneezing, sore throat, or cough.

Serious side effects and warnings

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

Brukinsa can cause the following serious or life-threatening side effects:

• Severe bleeding. Bleeding problems are common with Brukinsa, and can be serious and may
  lead to death. Your risk of bleeding may increase if you are also taking a blood thinner medicine. Tell your healthcare provider if you have any signs or symptoms of bleeding, including:
  • blood in your stools or black stools (looks like tar)
  • pink or brown urine
  • unexpected bleeding, or bleeding that is severe or you cannot control
  • increased bruising
  • dizziness
  • weakness
  • confusion
  • vomit blood or vomit that looks like coffee grounds
  • cough up blood or blood clots
  • change in speech
  • headache that lasts a long time.
• Infections that can be serious and may lead to death. Tell your healthcare provider right away if you have fever, chills, or flu-like symptoms
• Decrease in blood cell counts (white blood cells, platelets, and red blood cells). Your healthcare provider should do blood tests during treatment with Brukinsa to check your blood counts.
• Second primary cancers. New cancers have happened in people during treatment with Brukinsa, including cancers of the skin or other organs. Your healthcare provider will check you for other cancers during treatment. Use sun protection when you are outside in sunlight.
• Heart rhythm problems (atrial fibrillation, atrial flutter, and ventricular arrhythmias) that can be serious and may lead to death. Tell your healthcare provider if you have any of the following signs or symptoms:
  • your heartbeat is fast or irregular
  • feel lightheaded or dizzy
  • pass out (faint)
  • shortness of breath
  • chest discomfort.
• Liver problems. Liver problems, which may be severe or life-threatening, or lead to death, can happen in people treated with Brukinsa. Your healthcare provider will do blood tests to check your liver before and during treatment. Tell your healthcare provider or get medical help right away if you have any signs of liver problems, including stomach pain or discomfort, dark-colored urine, or yellow skin and eyes.

Brukinsa can cause fetal harm when administered to a pregnant woman, including malformations. Women should use effective contraception and avoid becoming pregnant while taking Brukinsa and for 1 week after the last dose. Men should avoid fathering a child during treatment and for 1 week after the last dose.

It is not known if Brukinsa is safe and effective in children.

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

Before taking

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

• have bleeding problems
• have had recent surgery or plan to have surgery. Your healthcare provider may stop Brukinsa for any planned medical, surgical, or dental procedure
• have an infection
• have or had heart rhythm problems
• have high blood pressure
• have liver problems, including a history of hepatitis B virus (HBV) infection
• take any other medicines, including prescription and over-the-counter medicines, vitamins, and herbal supplements
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Pregnancy

Brukinsa can harm your unborn baby. If you can become pregnant, your healthcare provider may do a pregnancy test before starting treatment with this medicine.

You may need to have a negative pregnancy test before you start using Brukinsa. Females should not become pregnant during treatment and for at least 1 week after the last dose. You should use effective birth control (contraception) during treatment and for at least 1 week after the last dose.

Males should avoid getting female partners pregnant during treatment and for at least 1 week after the last dose of Brukinsa. You should use effective birth control (contraception) during treatment and for at least 1 week after the last dose.

Breastfeeding

It is not known if Brukinsa passes into your breast milk. Do not breastfeed during treatment and for at least 2 weeks after your last dose.

How should I take Brukinsa?

Take exactly as directed by your healthcare provider. 

• Take the capsules/tablets once or twice daily as directed.
• Swallowed the capsules whole with a full glass of water. Do not open, break, or chew the capsules.
• The tablets can be split in half down the score line as prescribed by your healthcare provider. Do not chew or crush the tablets.
• May be taken with or without food. 
• The dosage may need to be reduced in those with severe liver disease.
• Take until disease progression or unacceptable toxicity occurs.

Dosing information

Adult dose of Brukinsa for MCL, WM, MZL, CLL, SLL, and FL:

• 160 mg twice a day or 320 mg once a day.
• May be taken with or without food.

Available as 80 mg capsules and 160 mg tablets.

Dosage reduction

The recommended dosage in severe liver disease is 80 mg twice daily.

• No dosage reduction is necessary in patients with mild or moderate hepatic impairment (Child-Pugh class A or B).

The dose also needs to be reduced when used with CYP3A Inhibitors or Inducers .

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 other drugs will affect Brukinsa?

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. Common medications that may interact with Brukinsa include:

• Moderate to strong CYP3A Inhibitors, such as clarithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, ritonavir, grapefruit juice, erythromycin, or verapamil
• Moderate to strong CYP3A inducers, such as glucocorticoids, rifampin, carbamazepine, phenobarbital, and phenytoin. Avoid coadministration.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking Brukinsa with certain other medications may affect how zanubrutinib works and can cause side effects.