Ibrutinib: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on May 20, 2024.

1. How it works

• Ibrutinib is an oral BTK inhibitor that may be used to treat several different cancers and graft versus host disease. Ibrutinib is available as the brand Imbruvica. There is no Imbruvica generic.
• Ibrutinib works by inhibiting the enzyme Bruton tyrosine kinase (BTK). BTK is part of a crucial signaling pathway in certain cancers, especially B-cell leukemias and lymphomas. By blocking this pathway, Ibrutinib blocks the signals that stimulate malignant cells to grow and divide out of control, triggering the death of cancerous cells.
• Ibrutinib belongs to the class of medicines known as Bruton tyrosine kinase inhibitors. It may also be called a targeted treatment.

2. Upsides

• Ibrutinib may be used to treat adults with chronic lymphocytic leukemia, small lymphocytic lymphoma (with or without 17p deletion), and Waldenstrom's macroglobulinemia.
• Ibrutinib may be used to treat chronic graft-versus-host disease (cGVHD) in adults and children older than 1 year after the failure of at least one other systemic treatment.
• Ibrutinib is not chemotherapy, it is a targeted treatment. Chemotherapy focuses primarily on the fact that cancer cells divide rapidly, so it kills all rapidly dividing cells (including healthy cells). Targeted treatments identify other features of cancer cells that are different from normal cells or are more overactive than normal cells.
• Ibrutinib is an oral tablet that is usually taken once daily in adults.
• Ibrutinib may be taken as a single agent, or in combination with other agents.
• No dose adjustment is required for people with mild or moderate kidney disease. Ibrutinib has not been studied in people with severe kidney disease. The dosage of Ibrutinib may need to be adjusted in those with mild or moderate liver disease. Avoid Ibrutinib in severe liver disease.
• Does not prolong the QT interval to any significant extent.
• Ibrutinib may be taken with or without food.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Diarrhea, fatigue, edema, nausea, pain, upper respiratory tract infections, rash, constipation, abdominal pain, vomiting, and bruising are the most common side effects reported.
• Other reported side effects include mouth ulcers, dyspepsia, fever, lack of energy, muscle spasms, joint pain, other infections (such as urinary tract infections, pneumonia, skin infections, or sinusitis), petechiae (tiny purple, red, or brown spots on the skin), shortness of breath, cough, nose bleeds, decreased appetite, dizziness, or headache. High lymphocyte counts are also common.
• High blood pressure has occurred in 19% of people; 8% experienced Grade 3 or greater hypertension. Monitor blood pressure and initiate or adjust blood pressure medication as needed.
• Ibrutinib can cause neutropenia, thrombocytopenia, and anemia. Temporarily stop Ibrutinib in people experiencing Grade 3 or greater non-hematological toxicities, Grade 3 or greater neutropenia with infection or fever, or Grade 4 hematological toxicities. Reinitiate ibrutinib at the starting dose once the adverse reaction has improved to Grade 1 or baseline (recovery). Reduce ibrutinib by 140mg/day if the adverse reaction reoccurs and consider a second reduction to 140 mg as needed. If side effects persist despite these dosage reductions, discontinue Ibrutinib.
• Ibrutinib is associated with an increased risk of other malignancies. Melanoma skin cancer was reported in 6% of people receiving ibrutinib and non-skin carcinomas in 4%.
• Ibrutinib is metabolized by CYP3A hepatic enzymes and strong CYP3A inhibitors such as clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal, and grapefruit should not be administered with Ibrutinib. The dosage of Ibrutinib will need to be reduced in people coadministered moderate CYP3A inhibitors, voriconazole, or posaconazole. After discontinuation of the CYP3A inhibitor, resume the previous dose of ibrutinib.
• The dosage of ibrutinib needs to be reduced in those with mild liver disease to 140 mg/day and moderate liver disease to 70 mg/day. Ibrutinib should not be used in people with severe liver disease.
• Major bleeding events, including intracranial hemorrhage, gastrointestinal bleeding, blood in the urine, and post-procedural hemorrhage, have occurred in 4% of patients who have received Ibrutinib; 0.4% of which were fatal. The risk is higher in those receiving anticoagulants or antiplatelet agents. Monitor people administered Ibrutinib for signs of bleeding and consider withholding ibrutinib for at least 3 to 7 days pre and post-surgery.
• Infections are common with ibrutinib and grade 3 or greater infections have occurred in 21% of patients receiving ibrutinib in clinical trials.
• Grade 3 or greater ventricular tachyarrhythmias have occurred in 0.2% of patients and Grade 3 or greater atrial fibrillation and atrial flutter have occurred in 4% of patients who received ibrutinib in clinical trials. The risk is greater in people with cardiac risk factors, high blood pressure, acute infections, and a previous history of cardiac arrhythmias. Periodically monitor patients clinically for cardiac arrhythmias. Obtain an ECG for patients who develop arrhythmic symptoms (such as palpitations, lightheadedness, syncope, chest pain) or new-onset shortness of breath and treat if necessary.
• Tumor Lysis Syndrome (TLS), which may lead to death, has been reported particularly in those with a high tumor burden before treatment. Monitor.
• Ibrutinib may harm a developing fetus. Advise women of childbearing potential to use effective contraception during Ibrutinib treatment and for one month following the final dose. There is also no data about the effects of ibrutinib on a newborn when breastfeeding. Advise women not to breastfeed during treatment with ibrutinib and for at least one week after the last dose. No effects on fertility have been reported.
• Ibrutinib is considered safe and effective in children older than 1 year when used to treat chronic Graft Versus Host Disease (cGVHD) after failure of one or more lines of systemic therapy.
• There is no generic ibrutinib, it is only available as the brand Imbruvica.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

• Ibrutinib is an oral tablet that may be taken once daily to treat certain types of cancers in adults or to treat chronic Graft Versus Host disease in adults and children older than 1 year. It works by inhibiting the enzyme Bruton tyrosine kinase (BTK) which is part of a crucial signaling pathway. Diarrhea and other gastrointestinal effects, high blood pressure, bruising, and infections are common side effects.

5. Tips

• Ibrutinib should be taken at approximately the same time each day with a glass of water. The capsules should be swallowed whole, do not break open, chew, or crush. If you miss a dose of ibrutinib, take the missed dose as soon as possible on the same day. However, if it is almost time for your next dose, do not double up the dose to make up for the extra dose, just return to your normal dosing schedule.
• Most people are kept on ibrutinib indefinitely regardless of clinical response. This is a common treatment strategy for people with certain types of leukemia and solid tumors because often when the treatment agent is stopped, symptoms can reappear and lymph nodes enlarge within a relatively short period, particularly if patients have not been taking ibrutinib for very long or if they have tried many other previous treatments.
• The recommended starting dose for ibrutinib varies depending on the condition being treated, but for adults, examples include Waldenstrom's macroglobulinemia, chronic or small lymphocytic leukemia, chronic graft-versus-host disease: 420mg once daily. Dosages may need reducing if toxicities occur.
• Copay assistance for ibrutinib (Imbruvica) is available under the YOU&I Support Program: Phone 1-877-877-3536 menu option 1, Monday to Friday 8 am-8 pm, and Saturdays 8 am to 5 pm. This program also offers support and contact with a nurse who can answer your questions, help address treatment challenges, and provide drug and disease information. People with commercial insurance may be able to get ibrutinib for as little as $10 per prescription.
• Keep your appointments with your healthcare provider. They must be able to monitor your response to ibrutinib. Your healthcare provider should do monthly blood tests to check you for side effects.
• Do not drink grapefruit juice or eat grapefruit products while you are taking ibrutinib as this may increase levels of ibrutinib in your body.
• Ibrutinib has been associated with some uncommon but serious side effects. Seek emergency medical help or call your doctor immediately if you experience any unusual bleeding, severe headache, yellow skin, severe upper right abdominal pain, chest pain, edema, shortness of breath, heart palpitations, itchy skin or skin reactions, dark urine, or other worrying side effects.
• See your doctor regularly for routine monitoring of your blood pressure, liver function, blood counts, and other vital signs.
• During initial treatment with ibrutinib, it is not uncommon to see an increase in white cell counts (lymphocytes). High lymphocyte counts have been reported in up to 57% to 69% of people in clinical trials. These resolved after 12 weeks in 95% of patients after ibrutinib was seen in 77 (57%) patients in group 1. This lasted for 12 to 14 weeks and resolved in 94% to 95% of these patients. Response to treatment and survival without cancer progression was similar in people with a high lymphocyte count during initial therapy and those without.
• Tell all healthcare professionals that you are taking ibrutinib. Ibrutinib can increase your risk of bleeding and may need to be withheld for at least 3 to 7 days before and after elective surgery.
• Your healthcare provider should do a pregnancy test before you start treatment with ibrutinib. Use effective contraception while receiving ibrutinib and for one month after the last dose. If you inadvertently become pregnant, see your doctor immediately. Males with female partners who can become pregnant should use effective birth control (contraception) during treatment and for one month after their last dose of ibrutinib. You should also not breastfeed while taking ibrutinib and for at least one week after the last dose.

6. Response and effectiveness

• In some people, very good partial clinical responses to ibrutinib may occur within three to six months.
• Ibrutinib is usually given until disease progression or unacceptable toxicity occurs, or in the case of graft vs. host disease, recurrence of an underlying malignancy.
• For CLL, the ORR for one trial was 58.3%, all were partial responses. None of the patients achieved a complete response. The DOR ranged from 5.6 to over 24 months. When ibrutinib was compared to ofatumumab, the ORR was 42.6% with ibrutinib and 4.1% with ofatumumab.
• For Waldenstrom's macroglobulinemia, 61.9% of people achieved a partial response or very good partial response. The mean duration of response was 2.8 months to over 18 months.
• For chronic graft versus host disease, the overall response rate was 67% and 48% responded for at least 20 weeks.
• Ibrutinib is usually given until disease progression or unacceptable toxicity occurs, or in the case of graft vs. host disease, recurrence of an underlying malignancy.
• The average duration of ibrutinib therapy in clinical trials has been around 41 months (range, 2–51 months). In people who have stopped ibrutinib, the average survival after treatment discontinuation was 8 months.
• High lymphocyte counts are a common and safe side effect that has been reported in 57% to 69% of people receiving ibrutinib in clinical trials. These resolve in over 94% of people within 14 weeks and are not a reflection of treatment response or cancer progression.

7. Interactions

Medicines that interact with ibrutinib may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with ibrutinib. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Ibrutinib interacts with over 360 medications; the majority of these interactions are considered moderate or major. Common medications that may interact with ibrutinib include:

• Antibiotics such as chloramphenicol, ciprofloxacin, or norfloxacin
• Anticoagulants, such as enoxaparin or heparin
• Antidepressants, such as citalopram or clomipramine
• Antifungals such as ketoconazole or voriconazole
• Antihistamines such as fexofenadine or terfenadine
• Antipsychotics, such as clozapine
• Antiseizure medications such as carbamazepine, fosphenytoin, phenytoin, or phenobarbitone
• Aprepitant
• Aspirin and NSAIDs such as ibuprofen, diclofenac, and sulindac
• barbiturates such as butabarbital
• Biologics, such as abciximab or adalimumab
• Corticosteroids, such as dexamethasone
• Digoxin
• Fingolimod
• Grapefruit juice
• Heart medications, such as amiodarone, quinidine, or verapamil
• Herbals, such as brewer's yeast or flax
• HIV medications, such as amprenavir, atazanavir, cobicistat, or efavirenz
• Immunosuppressants such as azathioprine, cyclosporine, or tacrolimus
• Iodine
• Lactobacillus
• Loperamide
• Omega-3 polyunsaturated fatty acids
• Mifepristone
• Quinidine
• Vaccinations, such as cholera, BCG vaccine, or zoster vaccine
• Warfarin.

Strong CYP3A4 enzyme inhibitors, such as ketoconazole, diltiazem, itraconazole, or grapefruit may increase blood concentrations of ibrutinib.

Strong CYP3A4 enzyme inducers, such as carbamazepine, rifampicin, phenytoin, phenobarbital, and St. John’s wort, may decrease blood concentrations of ibrutinib.

Note that this list is not all-inclusive and includes only common medications that may interact with ibrutinib. You should refer to the prescribing information for ibrutinib for a complete list of interactions.

References

• Imbruvica (ibrutinib) [Package insert]. Updated 03/2024. Pharmacyclics LLC. An AbbVie Company. Janssen. https://www.drugs.com/pro/imbruvica.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use ibrutinib only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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