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.

What is Imbruvica?

Imbruvica (ibrutinib) is used to treat chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), and chronic graft versus host disease (cGVHD) in certain patients. Imbruvica helps slow cancer progression in CLL, SLL, and WM and slow disease progression in cGVHD. 

Imbruvica is a targeted therapy it is not a a chemotherapy drug.

Imbruvica works by inhibiting the enzyme Bruton tyrosine kinase (BTK), which is part of a crucial signaling pathway in certain cancers, telling them to grow and divide uncontrollably.  By blocking Bruton tyrosine kinase, Imbruvica helps stop cancer cells from multiplying and triggers cancer cells to die.

Imbruvica is taken once a day as a capsule, tablet, or oral suspension.

Imbruvica FDA approval was first granted on November 13, 2013.

What is Imbruvica used for?

Imbruvica is FDA-approved (Imbruvica indications) for:

• chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in adults
• chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with 17p deletion in adults
• Waldenström’s macroglobulinemia (WM) in adults
• chronic graft versus host disease (cGVH), after failure of one or more lines of systemic therapy for adult and pediatric patients aged 1 year and older.

Imbruvica is no longer indicated for mantle cell lymphoma (MCL) or marginal zone lymphoma (MZL).

How does Imbruvica work?

Imbruvica’s mechanism of action is as a BTK inhibitor by directly inhibiting Bruton’s tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue on the enzyme, preventing its activity. BTK works as a signaling molecule for the B-cell antigen receptor (BCR) and cytokine receptor pathways. Activation of these pathways causes the proliferation of B cells and other interactions, and inhibition has been shown to reduce the growth and spread of malignant B cells. 

Imbruvica belongs to the class of medicines known as BTK inhibitors.

Imbruvica side effects

Common side effects of Imbruvica

Common Imbruvica side effects may include: 

• Diarrhea 59%
• Bruising 51%
• Upper respiratory tract infection 47%
• Fatigue, tiredness 33%
• Musculoskeletal pain 25%
• Rash 25%
• Fever 24%
• Joint pain 24%
• Constipation 22%
• Sinusitis 22%
• Cough 22%
• Swelling of extremities 22%
• Dizziness 20%
• Nausea 20%
• Mouth ulcers, stomatitis 20%
• Headache 18%
• Muscle spasms 18%
• Vomiting 18% 
• High blood pressure 16%
• Low appetitie 16% 
• Petechiae 16%
• Skin infection 16%
• Abdominal pain 14%
• Weakness, lack of energy and strength 14%
• Oropharyngeal pain, pain in the middle area or the throat 14%
• Chills 12%
• Difficulty breathing 12%
• Dyspepsia, indigestion 12%
• Pneumonia 12%
• Urinary tract infection 12%
• Second cancers 10%

These common side effects occurred in 10% or more of Imbruvica patients in the CLL/SLL clinical trial called Study 1102.

This medicine also cause blood test abnormalities including decreased platelets, neutrophils and hemoglobin levels. Your HCP will monitor your blood tests regularly.

Serious side effects of Imbruvica

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

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

• severe or ongoing diarrhea;
• heart problems – swelling, rapid weight gain, feeling short of breath;
• heart rhythm disorders – dizziness, chest pain, shortness of breath, fast or irregular heart rate, feeling light-headed;
• high blood pressure- severe headache, blurred vision, pounding in your neck or ears;
• 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;
• kidney problems – swelling, urinating less, feeling tired or short of breath;
• liver problems – stomach pain or discomfort, dark-colored urine, or yellow skin and eyes;
• 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.

Also see Warning section.

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. You may report side effects to the FDA .

Imbruvica for CLL

Imbruvica for CLL/SLL can be used for patients:

• as a first-line treatment or in patients who have previously had treatment for their cancer, and includes patients with or without a deletion in chromosome 17 (17p deletion). 
• in combination with Gazyva (obinutuzumab) for the treatment of previously untreated patients
• in combination with rituximab (Rituxan and other brands) for the treatment of previously untreated patients.

In CLL/SLL clinical trial RESONATE-2 (NCT01722487) Imbruvica significantly prolonged CLL/SLL overall survival with a relative risk of death that was 84% lower than chlorambucil at 24 months when used as monotherapy. The estimated CLL/SLL Imbruvica survival rate at 24 months was 98% versus 85% with chlorambucil.

The median progression-free survival (PFS) was not reached for Imbruvica compared to 18.9 months for chlorambucil. Imbruvica had a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil.

Warnings

Serious hemorrhage, including intracranial or gastrointestinal hemorrhage, hematuria, and post-procedural hemorrhage has occurred in people receiving Imbruvica, 0.4% have been fatal. 39% of people reported bleeding of any grade, including purpura and petechiae. Coadministration with antiplatelet or anticoagulants may increase the risk. Your doctor will monitor for signs and symptoms of bleeding and discontinue if serious bleeding occurs. They may consider withholding Imbruivca for 3 to 7 days pre and post surgery depending on the risk of bleeding. Call your doctor at once if you have signs of bleeding inside your body, such as dizziness, confusion, headache, speech problems, black or bloody stools, pink or brown urine, or coughing up blood or vomit that looks like coffee grounds.

Infections. This medication affects your immune system. Serious bacterial, viral, or fungal infections have been reported with Imbruvica; 21% were Grade 3 or higher. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred, in addition to reactivation of hepatitis B. Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections in patients who are at increased risk for infections. Tell your doctor if you have a fever, chills, cough, mouth sores, or other signs of infection.

Progressive multifocal leukoencephalopathy (PML) is a brain infection caused by a virus (polyomavirus JC) 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. Tell your doctor if you have a fever, chills, cough, mouth sores, or other signs of infection.

High blood pressure (hypertension) Hypertension as a side effect occurred in 19% of 1,476 patients with B-cell malignancies taking Imbruvica in clinical trials. Grade 3 or greater hypertension affects 8% of patients and the rate increases the longer the medicine is taken. BP should be measured regularly and treated as necessary.

Serious cardiac arrhythmias and cardiac disease, including atrial fibrillation, atrial flutter, ventricular arrhythmias, heart failure, and sudden death, have been reported in patients treated with Imbruvica. The risk is more likely in those with cardiac risk factors, high blood pressure, and acute infections. High blood pressure occurred in 19% of people prescribed Imbruvica in clinical trials. Monitor yourself for signs and symptoms of cardiac arrhythmias (such as palpitations, dizziness, dizziness when standing, and shortness of breath) and report these to your doctor immediately. Your doctor will check your blood pressure regularly.

Blood count abnormalities, including neutropenia, thrombocytopenia, and anemia, have occurred in people receiving Imbruvica. Your doctor will perform regular blood counts and interrupt treatment, reduce the dose, or discontinue treatment as warranted.

Second Primary Malignancies. Using Imbruvica may increase your risk of developing other cancers, such as non-melanoma skin cancer. Ask your doctor about this risk and what skin symptoms to watch for. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Tumor Lysis syndrome has been reported infrequently with Imbruvica. Symptoms include nausea and vomiting, diarrhea, and muscle cramps. If you have any symptoms like these, report them to your doctor.

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

Before taking this medicine

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

• an infection
• bleeding problems
• take a blood thinner such as warfarin
• a heart rhythm disorder
• risk factors for heart disease (such as diabetes, smoking, being overweight, having high blood pressure or high cholesterol)
• low blood cell counts
• recent surgery or plan to have surgery, medical or dental procedure
• liver disease.

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

Pregnancy

Ibrutinib can harm an unborn baby if the mother or the father is using this medication.

If you are a woman, you may need a pregnancy test to make sure you are not pregnant. Use birth control while using Imbruvica and for at least 1 month after your last dose. If you are a man, use birth control if your sex partner can get pregnant. Keep using birth control for at least 1 month after your last dose. Tell your doctor right away if a pregnancy occurs.

Breastfeeding

Do not breastfeed while using Imbruvica, and for at least 1 week after your last dose.

How should I take Imbruvica?

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

Take this medicine with a full glass of water, at the same time each day. Drink plenty of liquids while you are taking Imbruvica.

• Swallow the Imbruvica tablet or capsule whole and do not crush, chew, break, or open it.
• Shake the oral suspension (liquid). Measure a dose with the supplied measuring device (not a kitchen spoon), then take the medicine.

Tell your healthcare providers if you have a planned surgery.

You may get dehydrated during prolonged illness. Call your doctor if you are sick with vomiting or diarrhea.

You may get infections or bleed more easily. You will need frequent blood and medical tests.

Imbruvica dosing information

The dose of Imbruvica varies depending on the condition being treated:

Imbruvica Dosage for Adults with CLL/SLL and WM

• 420mg once daily.

Imbruvica Dosage for cGVHD

• Patients 12 years and older: 420mg once daily
• Patients 1 year old to less than 12 years old: 240mg/m² once daily (up to a maximum dosage of 420mg once daily).

Imbruvica Dosage forms and strengths

• Capsules: 70 mg and 140 mg
• Tablets: 140 mg, 280 mg, and 420 mg
• Oral suspension: 70 mg/mL

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 take 2 doses on the same day.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What should I avoid while taking this medicine?

Avoid grapefruit and Seville oranges with Imbruvica, as this may cause side effects. Avoid consuming grapefruit products and orange marmalades.

What other drugs will affect Imbruvica?

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.

• 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.

Other drugs may interact with ibrutinib, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all other medicines you use.

I

Imbruvica Package Insert 

HCPs and patients often use the Imbruvica Package Insert (PI) for more detailed information about this medicine. The Imbruvica Package Insert (prescribing information) 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 HCP (health care professional). 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 Imbruvica Prescribing Information (PI) or FDA label.

Imbruvica and Medicare

Because of the prescription drug law, known as the Inflation Reduction Act, Medicare is able to negotiate directly with drug companies to improve access to some of the costliest single-source brand-name Medicare Part B and Part D drugs.

Imbruvica is one of 10 drugs covered under Medicare Part D that were selected in 2024 for the first cycle of negotiation based on Total Expenditures under Part D and other criteria as required by the law. Negotiations with participating drug companies are ongoing, and any negotiated prices for the first cycle of negotiation is effective from 2026.

Ingredients

Active ingredient: ibrutinib.

• Tablets are supplied in three strengths: 140mg, 280mg, 420mg
• Capsules are supplied in two strengths: 70mg and 140mg
• Oral suspension: 70mg/mL. The bottle contains 108mL suspension in a 150mL bottle.

Inactive ingredients:

• Capsules: croscarmellose sodium, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate. The capsule shell contains gelatin, titanium dioxide, yellow iron oxide (70 mg capsule only), and black ink.
• Tablets: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, and sodium lauryl sulfate. The film coating for each tablet contains ferrosoferric oxide (140 mg, 280 mg, and 420 mg tablets), polyvinyl alcohol, polyethylene glycol, red iron oxide (280 mg tablets), talc, titanium dioxide, and yellow iron oxide (140 mg and 420 mg tablets).
• Oral suspension: benzyl alcohol, citric acid monohydrate, disodium hydrogen phosphate, hypromellose, microcrystalline cellulose, and carboxymethylcellulose sodium, purified water, and sucralose.

Jaypirca is a cancer medicine used to treat types of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). Jaypirca tablets may help to reduce the amount of CLL, SLL, and MCL, and for MCL it may remove the cancer. It can help treat cancer in patients who have already been treated with ibrutinib, acalabrutinib, or zanubrutinib (covalent BTK inhibitors), as it works differently than these cancer medicines.

Jaypirca FDA approval was received on January 27, 2023, as an accelerated approval based on response rate. Continued approval for these indications may depend on verification and description of clinical benefit in other trials.

Jaypirca tablet is an oral kinase inhibitor, and more specifically, it is a non-covalent (reversible) BTK inhibitor.

How does Jaypirca work?

Jaypirca’s mechanism of action (MOA) is that it blocks BTK, which is a signaling protein found across numerous B-cell leukemia and lymphomas, including MCL, CLL, and SLL, that, when stimulated, activates pathways responsible for B-cell proliferation, activity, and growth. This blocks the activity that leads to the growth of the B-cells and causes cell death of the malignant B-cells. Jaypirca belongs to the class of drugs called Bruton’s tyrosine kinase (BTK) inhibitors and is highly selective for BTK (300 times more selective than most other kinases).

What is Jaypirca used for?

Jaypirca FDA approval is for adult patients with:

• Relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of treatment, including a BTK inhibitor
• Chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two lines of treatment, including a Bruton’s tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

Jaypirca side effects

Common Jaypirca side effects

Common Jaypirca side effects may include bruising, tiredness, diarrhea, swelling, muscle, joint pain, bone pain, fever, chills, cough with mucus, chest pain, and feeling short of breath.

Serious Jaypirca 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.

Other serious Jaypirca side effects. Call your doctor at once if you have:

• chest pressure, racing or pounding heartbeats, fluttering in your chest, feeling short of breath;
• signs of infection – fever, chills, sore throat, body aches, unusual tiredness, loss of appetite, bruising or bleeding;
• bleeding inside your body – weakness, dizziness; pink or brown urine; abnormal vaginal bleeding; bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds; or
• 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.

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

Also, see the Warnings section.

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 .

Warnings

Infections. Serious and deadly infections caused by bacteria, viruses, or fungi have occurred with Jaypirca, 24% were Grade 3 or higher; opportunistic infections such as those caused by Pneumocystis jirovecci pneumonia also occurred. Consider prophylaxis, such as vaccinations and antibiotics in those at increased risk.

Bleeding. Serious and fatal bleeding events (hemorrhage) have also occurred with Jaypirca. Monitor for any signs of bleeding and manage appropriately.

Low blood cell counts. Lower than normal blood cell counts, including low neutrophils, platelets, or red blood cells, can occur. Your healthcare provider will monitor your blood counts regularly throughout treatment.

Liver problems which may be severe or life-threatening, or lead to death, can happen in people treated with Jaypirca. 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

Cardiac arrhythmia. Cardiac arrhythmias may occur, including atrial fibrillation and atrial flutter, and second primary cancers, including skin cancers, have also occurred. Use sun protection when outside.

Fetal Harm. This medicine can cause fetal harm. Females of reproductive potential should use effective contraception.

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

Before taking this medicine

Tell your doctor if you have or have ever had:

• an infection or have been told you are at an increased risk of infection;
• recent surgery, or plan to have surgery or a dental procedure;
• bleeding problems or are taking a blood thinner medicine;
• heart rhythm problems;
• high blood pressure;
• other types of cancer, including skin cancer; or
• kidney disease.

Pregnancy

Tell your healthcare provider if you are pregnant, plan to become pregnant or become pregnant, as this medicine may harm an unborn baby. Do not use this medicine if you are pregnant. Your healthcare provider will do a pregnancy test before starting treatment in females who can become pregnant. Females who are able to become pregnant should use effective birth control (contraception) during treatment and for 1 week after their last dose. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment.

Breastfeeding

Tell your healthcare provider if you are breastfeeding or planning to breastfeed, as it is not known if Jaypirca passes into your breast milk. Do not breastfeed during treatment and for 1 week after your last dose.

How should I take this medicine?

Jaypirca instructions

Take Jaypirca tablets 1 time each day at about the same time each day. Tablets can be taken with or without food. Tablets should be swallowed whole with water. Do not cut, crush, or chew the tablets.

General Information

Take Jaypirca tablets exactly as your healthcare provider tells you. Do not change your dose or stop treatment unless your healthcare provider tells you to do so.

You will need to have blood tests often.

Using this medicine may increase your risk of developing cancer. Ask your doctor about your individual risk.

Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Jaypirca Dosing Information

Usual Adult Dose of Jaypirca for CLL, SLL, and MCL
Dose: 200 mg orally once daily
Length of Therapy: Until disease progression or unacceptable toxicity occurs.
Comments: These indications are approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Use:

• For the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
• For the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two lines of treatment, including a Bruton’s tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

Jaypirca is available in 50 mg and 100 mg tablets.

What happens if I miss a dose?

If you miss a dose, take it as soon as you remember on the same day. If it has been more than 12 hours from the time you usually take Jaypirca, skip the missed dose, and take your next dose on the next day at your usual time.

What other drugs will affect Jaypirca?

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

Jaypirca interacts with other drugs that are metabolized in a certain way. Tell your doctor if you are taking medicines that contain any of the following drugs:

• strong CYP3A inhibitors: cobicistat, ritonavir, itraconazole, ketoconazole, posaconazole, voriconazole, ceritinib, clarithromycin, idelalisib, nefazodone, nelfinavir
• strong CYP3A inducers: apalutamide, carbamazepine, enzalutamide, ivosidenib, lumacaftor, mitotane, phenytoin, rifampin, St. John’s wort
• moderate CYP3A inducers: bosentan, cenobamate, dabrafenib, efavirenz, etravirine, lorlatinib, pexidartinib, phenobarbital, primidone, sotorasib