IMBRUVICA (Ibrutinib)
Bruton’s Tyrosine Kinase (BTK) Inhibitor for Blood Cancers
Quick Facts About IMBRUVICA
Key Takeaways About IMBRUVICA
- Targeted cancer therapy: IMBRUVICA selectively blocks Bruton’s tyrosine kinase (BTK), a key protein in B-cell signalling, to reduce cancer cell growth and promote cell death in CLL, MCL, and WM
- Continuous once-daily treatment: Taken as a single daily dose until disease progression or unacceptable toxicity – there is no fixed treatment duration or cycle
- Bleeding and cardiac risks: IMBRUVICA increases the risk of bleeding and can cause atrial fibrillation or heart failure, particularly in patients with pre-existing cardiac conditions
- Major drug interactions: Strong CYP3A4 inhibitors and inducers significantly affect ibrutinib levels – do not take with St. John’s Wort, grapefruit, or Seville oranges
- Not for use in pregnancy: IMBRUVICA may harm the unborn baby – effective contraception is required during treatment and for three months after stopping
What Is IMBRUVICA and What Is It Used For?
IMBRUVICA (ibrutinib) is a targeted anti-cancer medication that works by blocking Bruton’s tyrosine kinase (BTK), a protein that helps certain cancer cells grow and survive. It is approved for the treatment of chronic lymphocytic leukaemia (CLL), mantle cell lymphoma (MCL), and Waldenström’s macroglobulinaemia (WM) in adults.
IMBRUVICA belongs to a class of medicines called protein kinase inhibitors. Unlike traditional chemotherapy, which kills rapidly dividing cells indiscriminately, ibrutinib is a targeted therapy that specifically blocks a single enzyme – Bruton’s tyrosine kinase (BTK) – that plays a critical role in the survival and proliferation of B-lymphocytes. This targeted mechanism of action generally results in fewer side effects compared to conventional chemotherapy.
BTK is a key component of the B-cell receptor (BCR) signalling pathway. In healthy individuals, this pathway regulates the normal development, maturation, and function of B-cells (a type of white blood cell). However, in B-cell malignancies, the BCR signalling pathway becomes dysregulated, driving uncontrolled cancer cell growth. Ibrutinib forms a covalent (irreversible) bond with a specific amino acid (cysteine-481) in the BTK active site, permanently shutting down its enzymatic activity. This disruption stops the cancer cells from receiving the growth and survival signals they need, leading to cancer cell death (apoptosis) and preventing them from accumulating in the lymph nodes, blood, and bone marrow.
Chronic Lymphocytic Leukaemia (CLL)
CLL is the most common type of leukaemia in adults in Western countries. It is a slow-growing cancer of the B-lymphocytes that accumulate in the blood, bone marrow, lymph nodes, and spleen. IMBRUVICA is approved for CLL both as a first-line treatment (for patients who have not received any prior therapy) and for relapsed or refractory disease (when the cancer has returned after or failed to respond to previous treatments). Landmark clinical trials, including the RESONATE and RESONATE-2 studies, demonstrated that ibrutinib significantly improved progression-free survival and overall survival compared to standard treatments. The European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) both include ibrutinib as a recommended treatment option for CLL.
Mantle Cell Lymphoma (MCL)
MCL is a relatively rare but aggressive type of non-Hodgkin lymphoma that arises from B-lymphocytes in the “mantle zone” of the lymph node. IMBRUVICA is approved for adults with MCL who have not previously been treated and for whom stem cell transplantation would be appropriate, as well as for relapsed or refractory MCL. In clinical studies, ibrutinib achieved overall response rates of approximately 68% in relapsed/refractory MCL patients, with a complete response rate of around 21%. The treatment offers an important option for patients who may not be candidates for intensive chemotherapy or transplantation.
Waldenström’s Macroglobulinaemia (WM)
WM (also known as lymphoplasmacytic lymphoma) is a rare, slow-growing type of non-Hodgkin lymphoma characterised by overproduction of a protein called immunoglobulin M (IgM). IMBRUVICA is approved for WM both as first-line treatment and for relapsed/refractory disease, and is also indicated for patients for whom chemo-immunotherapy is not considered suitable. The pivotal iNNOVATE trial demonstrated superior progression-free survival for the combination of ibrutinib plus rituximab compared to placebo plus rituximab in WM patients.
IMBRUVICA was the first BTK inhibitor to receive regulatory approval. It was initially approved by the U.S. Food and Drug Administration (FDA) in November 2013 for MCL and subsequently received European Medicines Agency (EMA) approval in October 2014. Since then, it has become one of the most widely used targeted therapies in haematological oncology, with approvals in over 100 countries worldwide.
What Should You Know Before Taking IMBRUVICA?
Before starting IMBRUVICA, inform your doctor about all medical conditions – especially bleeding disorders, heart problems, liver disease, hepatitis B history, high blood pressure, and kidney problems. Do not take IMBRUVICA if you are allergic to ibrutinib or if you are taking St. John’s Wort.
IMBRUVICA is a powerful medication that requires careful medical supervision. Before prescribing it, your haematologist or oncologist will perform a thorough evaluation of your overall health, including blood tests, heart function assessment, and review of all current medications. It is essential that you provide your doctor with a complete medical history to ensure IMBRUVICA is safe for you.
Contraindications
You should not take IMBRUVICA if:
- You are allergic to ibrutinib or any of the other ingredients in the tablets (including lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, or sodium lauryl sulphate)
- You are taking St. John’s Wort (Hypericum perforatum), an herbal remedy used for mild depression and anxiety – this herbal medicine strongly reduces ibrutinib blood levels, making the treatment ineffective
If you are unsure about any of the above, consult your doctor, pharmacist, or nurse before taking IMBRUVICA.
Warnings and Precautions
Talk to your doctor, pharmacist, or nurse before taking IMBRUVICA if any of the following apply to you:
- Bleeding history or anticoagulant use: IMBRUVICA increases the risk of bleeding. Inform your doctor if you have ever had abnormal bruising or bleeding, or if you take any blood-thinning medications, antiplatelet agents, or supplements that increase bleeding risk (such as fish oil, vitamin E, or flaxseed)
- Heart rhythm problems: If you have ever had irregular heartbeats (arrhythmia), severe heart failure, or if you experience shortness of breath, weakness, dizziness, fainting, chest pain, or swollen legs, inform your doctor immediately. IMBRUVICA can cause atrial fibrillation and other cardiac events
- Liver problems: If you have hepatic impairment or a history of hepatitis B infection, your doctor will need to adjust your dose and monitor your liver function closely. IMBRUVICA can cause hepatitis B reactivation, which can be life-threatening
- High blood pressure: IMBRUVICA may worsen hypertension. Your blood pressure should be monitored regularly during treatment
- Recent or planned surgery: Your doctor may ask you to stop taking IMBRUVICA for 3 to 7 days before and after any surgical procedure, as the drug increases bleeding risk
- Kidney problems: Impaired kidney function may affect how IMBRUVICA is cleared from the body. Your doctor will monitor your kidney function during treatment
Signs of PML (Progressive Multifocal Leukoencephalopathy): Memory loss, difficulty thinking, trouble walking, or vision loss. This is a very rare but serious brain infection that can be fatal.
Signs of stroke: Sudden numbness or weakness (especially on one side), confusion, difficulty speaking, vision changes, loss of balance, or severe headache without known cause.
Splenic rupture symptoms (after stopping IMBRUVICA): Pain in the upper left abdomen, pain beneath the left ribcage, or pain at the tip of the left shoulder.
Effects on the Heart
Treatment with IMBRUVICA can affect the heart, particularly in patients with pre-existing cardiac conditions such as heart rhythm disorders, heart failure, or hypertension, as well as in patients with diabetes or advanced age. These cardiac effects can be serious and, in rare cases, fatal – including sudden cardiac death. Your doctor will assess your heart function before starting treatment and will monitor it periodically throughout your course of therapy.
You should immediately inform your doctor if you develop any of the following symptoms during treatment: shortness of breath, difficulty breathing when lying down, swelling of the feet, ankles, or legs, or unusual weakness or tiredness. These may be signs of heart failure.
Infections
During treatment with IMBRUVICA, you may develop viral, bacterial, or fungal infections. Your immune system is compromised by both the underlying cancer and the treatment itself, making you more susceptible to infections. Contact your doctor if you develop fever, chills, body aches, flu-like symptoms, fatigue, shortness of breath, or yellowing of the skin or eyes (jaundice). Severe infections, including sepsis and opportunistic infections, have been reported and may require hospitalisation and treatment interruption.
Pregnancy and Breastfeeding
IMBRUVICA should not be used during pregnancy. Based on its mechanism of action and animal studies, ibrutinib is expected to cause harm to the developing baby. Women of childbearing potential must use a highly effective method of contraception during treatment and for at least three months after the last dose of IMBRUVICA. If you become pregnant while taking IMBRUVICA, inform your doctor immediately.
You should not breastfeed while taking IMBRUVICA, as it is not known whether ibrutinib passes into human breast milk. A risk to the nursing infant cannot be excluded.
Driving and Operating Machinery
You may feel tired or dizzy after taking IMBRUVICA, which can affect your ability to drive or operate machinery. If you experience these symptoms, do not drive or use tools or machines until the symptoms have resolved.
Important Information About Ingredients
IMBRUVICA tablets contain lactose (a type of sugar). If you have been told by your doctor that you have an intolerance to certain sugars, contact your doctor before taking this medicine. The tablets contain less than 1 mmol (23 mg) of sodium per dose, meaning they are essentially sodium-free.
How Does IMBRUVICA Interact with Other Drugs?
IMBRUVICA has significant drug interactions due to its metabolism via CYP3A4. Strong CYP3A4 inhibitors (ketoconazole, posaconazole, clarithromycin, ritonavir) dramatically increase ibrutinib levels and require dose adjustment or avoidance. Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, St. John’s Wort) drastically reduce its effectiveness. Blood thinners and NSAIDs increase bleeding risk.
Ibrutinib is primarily metabolised by the liver enzyme CYP3A4, making it highly susceptible to drug interactions with medications that either inhibit or induce this enzyme. Additionally, IMBRUVICA affects platelet function, which can increase the risk of bleeding when combined with anticoagulants or antiplatelet agents. Always tell your doctor about all medications you are taking, including over-the-counter drugs, herbal remedies, and dietary supplements.
Major Interactions – Avoid or Adjust Dose
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Ketoconazole / Posaconazole / Voriconazole | Strong antifungals | Strong CYP3A4 inhibitors; can increase ibrutinib levels up to 29-fold | Avoid concurrent use or reduce IMBRUVICA dose significantly; use fluconazole as alternative |
| Clarithromycin / Telithromycin | Macrolide antibiotics | Strong CYP3A4 inhibitors; markedly increase ibrutinib exposure | Avoid concurrent use; consider azithromycin as alternative (minimal CYP3A4 inhibition) |
| Ritonavir / Cobicistat / Indinavir | HIV protease inhibitors / boosters | Strong CYP3A4 inhibitors; dramatically increase ibrutinib levels | Avoid concurrent use if possible; if unavoidable, reduce IMBRUVICA dose |
| Rifampicin | Antibiotic (tuberculosis) | Strong CYP3A4 inducer; reduces ibrutinib levels by approximately 90% | Avoid concurrent use – IMBRUVICA will be rendered ineffective |
| Carbamazepine / Phenytoin | Anti-epileptic drugs | Strong CYP3A4 inducers; markedly reduce ibrutinib blood levels | Avoid concurrent use; consider alternative anti-epileptic agents |
| St. John’s Wort (Hypericum perforatum) | Herbal supplement | Strong CYP3A4 inducer; dramatically reduces ibrutinib effectiveness | Contraindicated – must not be taken with IMBRUVICA |
| Warfarin / Heparin | Anticoagulants | IMBRUVICA increases bleeding risk; combined use significantly raises haemorrhage risk | Use with extreme caution; monitor closely for bleeding; consider alternatives if possible |
Moderate Interactions – Use with Caution
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Fluconazole / Erythromycin / Ciprofloxacin | Moderate CYP3A4 inhibitors | Moderately increase ibrutinib blood levels | Reduce IMBRUVICA dose to 280 mg daily during co-administration |
| Diltiazem / Verapamil | Calcium channel blockers | Moderate CYP3A4 inhibitors; increase ibrutinib levels and may have additive cardiac effects | Reduce IMBRUVICA dose; monitor heart rhythm and blood pressure closely |
| Ibuprofen / Naproxen / Aspirin | NSAIDs / Antiplatelet | Additive increase in bleeding risk due to combined antiplatelet effects | Use with caution; monitor for signs of bleeding; use paracetamol for pain relief when possible |
| Amiodarone / Dronedarone | Antiarrhythmic drugs | CYP3A4 inhibitors; may increase ibrutinib levels and have additive cardiac effects | Monitor heart rhythm closely; dose adjustment may be required |
| Aprepitant | Anti-emetic | Moderate CYP3A4 inhibitor; may increase ibrutinib exposure | Monitor for increased IMBRUVICA side effects during concurrent use |
| Rosuvastatin | Statin (cholesterol-lowering) | IMBRUVICA may increase rosuvastatin blood levels | Monitor for statin-related side effects (muscle pain, liver function) |
| Digoxin / Methotrexate | Cardiac glycoside / Immunosuppressant | IMBRUVICA may alter their blood levels via P-glycoprotein inhibition | Take digoxin or methotrexate at least 6 hours before or after IMBRUVICA |
Do not eat grapefruit or Seville oranges (bitter oranges), drink their juice, or take supplements containing these fruits while on IMBRUVICA. These fruits inhibit CYP3A4 and can unpredictably increase ibrutinib blood levels, raising the risk of serious side effects.
What Is the Correct Dosage of IMBRUVICA?
The dosage of IMBRUVICA depends on the condition being treated: 560 mg once daily for MCL, and 420 mg once daily for CLL and WM. Take the tablets at approximately the same time each day with a glass of water. Swallow tablets whole – do not crush or chew them.
Always take IMBRUVICA exactly as your doctor, pharmacist, or nurse has instructed. IMBRUVICA is a continuous treatment, meaning you take it every day until your doctor tells you to stop. Unlike conventional chemotherapy, there are no treatment cycles or rest periods. The tablets should be taken orally with a glass of water at approximately the same time each day.
Mantle Cell Lymphoma (MCL)
MCL Dosage
Recommended dose: 560 mg (four 140 mg tablets) once daily
This dose applies to both previously untreated MCL patients and those with relapsed/refractory disease. Your doctor may adjust your dose based on side effects and blood test results.
Chronic Lymphocytic Leukaemia (CLL) and Waldenström’s Macroglobulinaemia (WM)
CLL / WM Dosage
Recommended dose: 420 mg (three 140 mg tablets) once daily
This dose applies to first-line and relapsed/refractory CLL and WM. IMBRUVICA may be used alone or in combination with other treatments such as rituximab or obinutuzumab, depending on clinical circumstances.
Dose Adjustments
Your doctor may reduce your dose if you experience significant side effects or if you need to take certain other medications that interact with ibrutinib. Common dose reduction steps include reducing from 420 mg to 280 mg to 140 mg, or from 560 mg to 420 mg to 280 mg to 140 mg. If the side effects resolve, your doctor may increase the dose back to the original level.
When IMBRUVICA is used with moderate CYP3A4 inhibitors (such as fluconazole, erythromycin, or diltiazem), the dose should be reduced to 280 mg daily. With strong CYP3A4 inhibitors (such as ketoconazole or posaconazole), the dose may be reduced further or the combination should be avoided entirely.
Children and Adolescents
IMBRUVICA is not approved for use in children or adolescents under 18 years of age. The safety and efficacy of ibrutinib have not been established in this population.
Missed Dose
If you miss a dose of IMBRUVICA, take it as soon as possible on the same day, then return to your normal schedule the following day. Do not take a double dose to make up for a forgotten dose. If you are unsure about when to take your next dose, speak to your doctor, pharmacist, or nurse.
Overdose
If you take more IMBRUVICA than you should, contact your doctor immediately or go to the nearest hospital emergency department. Take the tablet packaging and this information with you. Symptoms of overdose may include increased bleeding, irregular heartbeat, or severe fatigue. There is no specific antidote for ibrutinib overdose – treatment is supportive.
If You Stop Taking IMBRUVICA
Do not stop taking IMBRUVICA unless your doctor tells you to. Abruptly discontinuing treatment can lead to rapid disease recurrence or “flare” of the underlying cancer. Some patients have experienced splenic rupture after stopping ibrutinib – contact your doctor immediately if you develop pain in the upper left abdomen after discontinuation.
If you are scheduled for any surgical procedure, tell your surgeon that you are taking IMBRUVICA. Your doctor may instruct you to stop taking IMBRUVICA for 3 to 7 days before the procedure and to restart it once adequate wound healing has occurred, typically 1–3 days after minor surgery and longer after major procedures.
What Are the Side Effects of IMBRUVICA?
Like all cancer therapies, IMBRUVICA can cause side effects. The most common include infections, bleeding and bruising, diarrhoea, musculoskeletal pain, nausea, rash, high blood pressure, and low blood cell counts. Serious side effects include atrial fibrillation, severe infections (sepsis), and bleeding events. Most side effects can be managed with dose adjustments or supportive care.
Not everyone who takes IMBRUVICA will experience side effects, and most are manageable. However, because ibrutinib affects several biological pathways beyond BTK, it can cause a range of adverse events. Your treatment team will regularly monitor you with blood tests and clinical assessments. It is important to report any new or worsening symptoms promptly, as early intervention can often prevent complications.
Itchy raised rash, difficulty breathing, swelling of the face, lips, tongue, or throat – you may be having an allergic reaction to the medicine. Severe allergic reactions (angioedema) and Stevens-Johnson syndrome have been reported rarely.
Side Effects by Frequency (B-cell Malignancies)
Very Common (more than 1 in 10 patients)
These effects occur in more than 10% of patients
- Infections – viral, bacterial, or fungal (upper respiratory tract, pneumonia, skin infections, urinary tract infections)
- Bleeding and bruising – blood in stool or urine, nosebleeds, heavy menstrual periods, easy bruising, petechiae (small red/purple spots under the skin)
- Diarrhoea
- Nausea and vomiting
- Constipation
- Mouth sores (stomatitis)
- Headache and dizziness
- Skin rash
- Pain in arms, legs, back, joints, or muscles; muscle cramps and spasms
- Fever
- Swelling of hands, ankles, or feet (peripheral oedema)
- High blood pressure (hypertension)
- Low platelet count (thrombocytopenia) and low white blood cell count (neutropenia) – seen in blood tests
- Increased lymphocyte count (lymphocytosis) – expected during early weeks of treatment
- Elevated blood creatinine
- Indigestion (dyspepsia)
Common (up to 1 in 10 patients)
These effects occur in 1–10% of patients
- Severe infections throughout the body (sepsis)
- Urinary tract infections
- Heart failure
- Irregular heartbeat (atrial fibrillation), skipped heartbeats, weak or uneven pulse, palpitations
- Febrile neutropenia (low white cells with fever)
- Non-melanoma skin cancers (squamous cell carcinoma, basal cell carcinoma)
- Blurred vision
- Skin redness (erythema) and hives (urticaria)
- Lung inflammation (pneumonitis) – may cause permanent damage
- Elevated uric acid levels (which may cause gout)
- Brittle or broken nails
- Acute kidney injury
- Peripheral neuropathy (weakness, numbness, tingling, or pain in hands, feet, or other body parts)
Uncommon (up to 1 in 100 patients)
These effects occur in 0.1–1% of patients
- Liver failure, including fatal cases
- Severe fungal infections
- Hepatitis B reactivation
- Bleeding on the surface of the brain (subdural haematoma)
- Tumour lysis syndrome (abnormal blood chemistry from rapid cancer cell breakdown)
- Severe allergic reaction (angioedema) – swelling of face, lips, mouth, tongue, or throat
- Stroke or transient ischaemic attack
- Eye bleeding (sometimes with vision loss) and inflammation inside the eye (uveitis)
- Cardiac arrest (heart stops beating)
- Abnormally rapid heartbeat (ventricular tachycardia)
- Pyoderma gangrenosum (painful skin ulcers) and Sweet’s syndrome (acute febrile neutrophilic dermatosis)
- Pyogenic granuloma (small red raised skin lesion that bleeds easily)
- Cutaneous vasculitis (inflamed blood vessels in the skin)
- Inflammation of fat tissue under the skin (panniculitis)
- Haemophagocytic lymphohistiocytosis (HLH) – overactivation of white blood cells causing severe inflammation
Rare (up to 1 in 1,000 patients)
These effects occur in less than 0.1% of patients
- Leukostasis – markedly elevated white blood cell count causing cells to clump together and obstruct small blood vessels
- Stevens-Johnson syndrome – severe skin reaction with blistering and peeling, especially around the mouth, nose, eyes, and genitals
Lymphocyte Count Increase
During the first weeks of treatment, laboratory tests may show an increase in white blood cells called lymphocytes in the blood. This is an expected pharmacological effect of IMBRUVICA: as ibrutinib inhibits BTK, cancer cells are released from the lymph nodes and spleen into the bloodstream. This “lymphocytosis” does not mean the disease is worsening. It typically resolves within a few months and does not require a change in treatment. Your doctor will monitor your blood counts to confirm this is the expected pattern.
Reporting suspected side effects after a medicine has been authorised is important. It allows continuous monitoring of the medicine’s benefit-risk balance. Healthcare professionals and patients are encouraged to report suspected adverse reactions through their national pharmacovigilance system (e.g., the Yellow Card Scheme in the UK, MedWatch in the US, or the EMA in Europe).
How Should You Store IMBRUVICA?
Store IMBRUVICA at room temperature, out of sight and reach of children. No special storage conditions are required. Do not use after the expiry date printed on the packaging.
Keep IMBRUVICA tablets in their original packaging to protect them from light and moisture. There are no special temperature requirements for this medication – standard room temperature storage is adequate. Check the expiry date (marked “EXP”) on the outer carton before taking each dose, and do not use the tablets after this date. The expiry date refers to the last day of the stated month.
Do not dispose of IMBRUVICA tablets in household waste or down the drain. Ask your pharmacist about safe disposal of medicines you no longer need. These measures help to protect the environment from potential contamination with cytotoxic substances.
What Does IMBRUVICA Contain?
Each IMBRUVICA film-coated tablet contains ibrutinib as the active substance. Tablets are available in four strengths: 140 mg, 280 mg, 420 mg, and 560 mg. Inactive ingredients include lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate.
Active Ingredient
The active substance is ibrutinib. Each tablet strength contains exactly the amount stated on the packaging:
- IMBRUVICA 140 mg: Each tablet contains 140 mg ibrutinib
- IMBRUVICA 280 mg: Each tablet contains 280 mg ibrutinib
- IMBRUVICA 420 mg: Each tablet contains 420 mg ibrutinib
- IMBRUVICA 560 mg: Each tablet contains 560 mg ibrutinib
Inactive Ingredients
The other ingredients are:
- Tablet core: Colloidal anhydrous silica, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulphate (E487)
- Film coating: Polyvinyl alcohol, macrogol, talc, titanium dioxide (E171)
The 140 mg and 420 mg tablets also contain black iron oxide (E172) and yellow iron oxide (E172). The 280 mg tablets contain black iron oxide (E172) and red iron oxide (E172). The 560 mg tablets contain red iron oxide (E172) and yellow iron oxide (E172).
Tablet Appearance and Pack Sizes
| Strength | Appearance | Size | Pack |
|---|---|---|---|
| 140 mg | Yellow-green to green, round; imprinted “ibr” / “140” | 9 mm diameter | 28 or 30 film-coated tablets |
| 280 mg | Purple, oblong; imprinted “ibr” / “280” | 15 mm × 7 mm | 28 or 30 film-coated tablets |
| 420 mg | Yellow-green to green, oblong; imprinted “ibr” / “420” | 17.5 mm × 7.4 mm | 28 or 30 film-coated tablets |
| 560 mg | Yellow to orange, oblong; imprinted “ibr” / “560” | 19 mm × 8.1 mm | 28 or 30 film-coated tablets |
Frequently Asked Questions About IMBRUVICA
IMBRUVICA (ibrutinib) is used to treat several types of blood cancer in adults: chronic lymphocytic leukaemia (CLL), mantle cell lymphoma (MCL), and Waldenström’s macroglobulinaemia (WM). It works by blocking Bruton’s tyrosine kinase (BTK), a protein that cancer cells need to grow and survive. It can be used as a first-line treatment or when the disease has relapsed or not responded to prior therapy.
The most common side effects of IMBRUVICA (occurring in more than 1 in 10 patients) include infections (upper respiratory, pneumonia, skin infections), bleeding and bruising, diarrhoea, nausea, constipation, headache, dizziness, musculoskeletal pain, rash, high blood pressure, fatigue, and low platelet counts. Most side effects are manageable with dose adjustments or supportive care. Your doctor will monitor you regularly with blood tests.
IMBRUVICA has important drug interactions. You must not take it with St. John’s Wort. Strong CYP3A4 inhibitors (ketoconazole, posaconazole, clarithromycin, ritonavir) significantly increase ibrutinib levels and require dose reduction or avoidance. Blood thinners and NSAIDs increase bleeding risk. Grapefruit and Seville oranges should also be avoided. Always inform your doctor about all medications, supplements, and herbal products you are taking.
IMBRUVICA is a continuous treatment taken once daily until disease progression or unacceptable side effects occur. Unlike traditional chemotherapy, there is no fixed number of treatment cycles. Many patients take IMBRUVICA for years. It is critically important not to stop taking it without your doctor’s guidance, as sudden discontinuation can lead to rapid disease progression. If you need surgery, your doctor may temporarily pause treatment for 3–7 days.
Yes, IMBRUVICA can affect the heart. Atrial fibrillation (irregular heartbeat) is a common side effect occurring in up to 1 in 10 patients. Heart failure and, rarely, cardiac arrest have also been reported. Patients with pre-existing heart conditions, diabetes, or advanced age are at higher risk. Your doctor will monitor your heart function before and during treatment. Report any symptoms such as shortness of breath, chest discomfort, palpitations, dizziness, or fainting immediately.
No, IMBRUVICA should not be used during pregnancy as it may cause harm to the developing baby. Women of childbearing potential must use highly effective contraception during treatment and for at least three months after stopping IMBRUVICA. You should not breastfeed while taking this medicine, as it is not known whether ibrutinib passes into breast milk. If you become pregnant or suspect pregnancy, contact your doctor immediately.
References
- European Medicines Agency (EMA). IMBRUVICA – Summary of Product Characteristics (SmPC). Available at: ema.europa.eu/imbruvica. Last updated 2025.
- Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32–42. doi:10.1056/NEJMoa1215637.
- Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369(6):507–516. doi:10.1056/NEJMoa1306220.
- Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia (RESONATE-2). N Engl J Med. 2015;373(25):2425–2437. doi:10.1056/NEJMoa1509388.
- Dimopoulos MA, Tedeschi A, Trotman J, et al. Phase 3 trial of ibrutinib plus rituximab in Waldenström’s macroglobulinemia (iNNOVATE). N Engl J Med. 2018;378(25):2399–2410. doi:10.1056/NEJMoa1802917.
- European Society for Medical Oncology (ESMO). Chronic Lymphocytic Leukaemia: Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. Ann Oncol. 2024.
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Version 2.2025.
- World Health Organization (WHO). Model List of Essential Medicines, 23rd edition. Geneva: WHO; 2023.
- U.S. Food and Drug Administration (FDA). IMBRUVICA Prescribing Information. Revised 2025.
- National Institute for Health and Care Excellence (NICE). Ibrutinib for treating chronic lymphocytic leukaemia. Technology Appraisal Guidance [TA429]. 2017; updated 2024.
Editorial Team
Medical review process: This article has been reviewed by the iMedic Medical Editorial Team, comprising board-certified haematologists, oncologists, and clinical pharmacologists. All medical claims are supported by peer-reviewed evidence at the highest quality level (Evidence Level 1A – systematic reviews and meta-analyses of randomised controlled trials).
Medical Content
iMedic Medical Editorial Team – Specialist Physicians in Haematology and Clinical Pharmacology
Clinical Review
iMedic Medical Review Board – Independent Expert Panel
Guidelines followed: WHO Guidelines, ESMO Clinical Practice Guidelines (2024), NCCN Guidelines (2025), NICE Technology Appraisals, GRADE evidence framework. Conflict of interest: None. Funding: No commercial funding. Independent medical editorial content.