Ibrutinib Side Effects

Medically reviewed by Philip Thornton, DipPharm. Last updated on Feb 15, 2024.

Applies to ibrutinib: oral capsule, oral suspension, oral tablet.

Serious side effects of ibrutinib

Along with its needed effects, ibrutinib may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking ibrutinib:

More common

• back pain
• bladder pain
• bloating or swelling of the face, arms, hands, lower legs, or feet
• bloody or black, tarry stools
• bloody or cloudy urine
• blurred vision
• body aches or pain
• chest pain or tightness
• chills
• confusion
• cough
• decreased frequency or amount of urine
• difficult, burning, or painful urination
• dizziness or lightheadedness
• drowsiness
• dry mouth
• fainting
• fast or irregular heartbeat
• fever
• frequent urge to urinate
• headache
• hoarseness
• increased thirst
• irregular heartbeat
• itching
• loss of appetite
• lower back or side pain
• nausea
• rapid weight gain
• seizures
• severe headache
• severe stomach pain
• sore throat
• tingling of the hands or feet
• trouble breathing
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• vomiting
• vomiting of blood or material that looks like coffee grounds
• wrinkled skin

Less common

• persistent non-healing sore
• pink skin growth
• reddish skin patch or irritated area
• shiny skin bump
• white, yellow or waxy scar-like area on the skin

Incidence not known

• blistering, peeling, or loosening of the skin
• dark urine
• diarrhea
• dilated neck veins
• difficulty swallowing
• general feeling of tiredness or weakness
• hives, skin rash
• joint pain, stiffness, or swelling
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
• light-colored stools
• muscle pain
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes
• yellow eyes or skin

Other side effects of ibrutinib

Some side effects of ibrutinib may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• belching
• decreased appetite
• difficulty having a bowel movement
• heartburn or indigestion
• indigestion
• lack or loss of strength
• muscle stiffness or spasms
• small red or purple spots on the skin
• stomach discomfort, upset, or pain
• swelling or inflammation of the mouth

For healthcare professionals

Applies to ibrutinib: oral capsule, oral suspension, oral tablet.

General

The most common adverse reactions in patients with B-cell malignancies were thrombocytopenia, diarrhea, fatigue, musculoskeletal pain, neutropenia, rash, anemia, bruising, nausea, hemorrhage, arthralgia, and upper respiratory tract infection.

The most common adverse reactions in patients with chronic graft-versus-host disease were fatigue, anemia, bruising, diarrhea, thrombocytopenia, musculoskeletal pain, pyrexia, muscle spasms, stomatitis, hemorrhage, nausea, abdominal pain, pneumonia, and headache.^[Ref]

Cardiovascular

• Very common (10% or more): Hypertension (up to 42%), atrial fibrillation (up to 15%), sinus tachycardia (up to 11%)
• Common (1% to 10%): Atrial flutter, cardiac failure, ventricular tachyarrhythmias (includes ventricular extrasystoles, ventricular arrhythmias, ventricular fibrillation, ventricular flutter, ventricular tachycardia), deaths due to cardiac causes/sudden deaths
• Uncommon (0.1% to 1%): Cardiac arrest
• Frequency not reported: Cardiac arrhythmias
• Postmarketing reports: Cardiac failure, ventricular tachyarrhythmia

Hypertension occurred in 19% of 1476 patients with B-cell malignancies who received this drug in clinical trials; grade 3 or greater hypertension occurred in 8% of patients. Based on data from a subset of these patients (N=1124), the median time to onset was 5.9 months (range: 0 to 24 months). In a long-term safety analysis over 5 years of 1284 patients with B-cell malignancies treated for a median of 36 months (range: 0 to 98 months), the cumulative rate of hypertension increased over time. The prevalence for grade 3 or greater hypertension was 4% (year 0 to 1), 7% (year 1 to 2), 9% (year 2 to 3), 9% (year 3 to 4), and 9% (year 4 to 5); the overall incidence for the 5-year period was 11%.

Fatal and serious cardiac arrhythmias and cardiac failure have occurred with this drug. Deaths due to cardiac causes or sudden deaths occurred in 1% of 4896 patients who received this drug in clinical trials, including in those who received this drug in unapproved monotherapy or combination regimens. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities.

Grade 3 or greater ventricular tachyarrhythmias were reported in 0.2%, grade 3 or greater atrial fibrillation and atrial flutter were reported in 3.7%, and grade 3 or greater cardiac failure was reported in 1.3% of 4896 patients who received this drug in clinical trials, including in those who received this drug in unapproved monotherapy or combination regimens, and especially in patients with acute infections or cardiac risk factors (including hypertension, diabetes mellitus, history of cardiac arrhythmias).

Dermatologic

• Very common (10% or more): Bruising/contusion (up to 51%), rash (up to 49%), petechiae (up to 16%), skin infection (up to 18%), pruritus (up to 13%)
• Common (1% to 10%): Erythema, urticaria
• Uncommon (0.1% to 1%): Angioedema
• Postmarketing reports: Angioedema, urticaria, Stevens-Johnson syndrome, onychoclasis, panniculitis, neutrophilic dermatoses, erythema

Gastrointestinal

• Very common (10% or more): Diarrhea (up to 59%), nausea (up to 40%), stomatitis (up to 29%), abdominal pain (up to 23%), constipation (up to 22%), vomiting (up to 19%), dyspepsia (up to 16%), gastroesophageal reflux disease (up to 12%)

Genitourinary

• Very common (10% or more): Urinary tract infection (up to 13%)

Hematologic

• Very common (10% or more): Decreased platelets (up to 69%), neutropenia (up to 66%), decreased neutrophils (up to 55%), decreased hemoglobin (up to 49%), bleeding events (including bruising, petechiae; up to 39%), thrombocytopenia (up to 36%), hemorrhage (up to 32%), anemia (up to 17%), lymphocytosis (up to 15%)
• Common (1% to 10%): Major hemorrhage (e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, postprocedural hemorrhage), febrile neutropenia, leukocytosis, subdural hematoma
• Uncommon (0.1% to 1%): Fatal bleeding events, leukostasis syndrome

Fatal bleeding events have occurred in patients who received this drug. Major hemorrhage (grade 3 or greater, serious, or any central nervous system events, e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and postprocedural hemorrhage) occurred in 4.2% of patients, with fatalities occurring in 0.4% of 2838 patients who received this drug in 27 clinical trials. Bleeding events (any grade) including bruising and petechiae occurred in 39% and excluding bruising and petechiae occurred in 23% of patients who received this drug, respectively.

Across clinical trials, 3.1% of 2838 patients who received this drug without antiplatelet or anticoagulant therapy experienced major hemorrhage. The addition of antiplatelet therapy (with or without anticoagulant therapy) increased the incidence to 4.4%, and the addition of anticoagulant therapy (with or without antiplatelet therapy) increased the incidence to 6.1%.

In 645 patients with B-cell malignancies who received this drug as a single agent, grade 3 or 4 neutropenia occurred in 23% of patients, grade 3 or 4 thrombocytopenia in 8% of patients, and grade 3 or 4 anemia in 2.8% of patients, based on laboratory measurements.

Hepatic

• Very common (10% or more): Increased bilirubin (up to 30%), increased AST (up to 25%), increased ALT (up to 11%)
• Postmarketing reports: Hepatic failure (including acute events, fatal events), hepatic cirrhosis, hepatitis B reactivation, hepatotoxicity

Hypersensitivity

• Postmarketing reports: Anaphylactic shock

Immunologic

• Very common (10% or more): Hypogammaglobulinemia (up to 11%)

Metabolic

• Very common (10% or more): Hyperuricemia (up to 19%), decreased appetite (up to 16%), hypokalemia (up to 15%)
• Common (1% to 10%): Tumor lysis syndrome, hyponatremia
• Postmarketing reports: Tumor lysis syndrome

Musculoskeletal

• Very common (10% or more): Musculoskeletal pain (up to 61%), arthralgia (up to 41%), muscle spasms (up to 29%), osteonecrosis (up to 11%)

Nervous system

• Very common (10% or more): Headache (up to 40%), dizziness (up to 21%), peripheral neuropathy (up to 19%)
• Common (1% to 10%): Ischemic cerebrovascular events (includes cerebrovascular accidents, ischemic stroke, cerebral ischemia, transient ischemic attack)
• Frequency not reported: Progressive multifocal leukoencephalopathy
• Postmarketing reports: Peripheral neuropathy, cerebrovascular accident, transient ischemic attack, ischemic stroke

Ocular

• Very common (10% or more): Dry eye (up to 17%), blurred vision (up to 13%), increased lacrimation (up to 13%), reduced visual acuity (up to 11%), conjunctivitis (up to 11%)
• Postmarketing reports: Eye hemorrhage

Oncologic

• Very common (10% or more): Second malignancies (10%), other malignancies (including nonskin carcinomas; 10%)
• Common (1% to 10%): Nonmelanoma skin cancer, nonskin carcinomas, basal cell carcinoma, squamous cell carcinoma
• Frequency not reported: Histiocytic sarcoma

Other malignancies (10%), including nonskin carcinomas (3.9%), occurred among the 1476 patients with B-cell malignancies who received this drug in clinical trials. The most frequent second primary malignancy was nonmelanoma skin cancer (6%).

Other

• Very common (10% or more): Fatigue (up to 80%), pyrexia (up to 30%), peripheral edema (up to 28%), infusion related reaction (up to 25%), pain (up to 23%), infections (at least 21%), fall (up to 17%), asthenia (up to 14%), chills (up to 12%), sepsis (up to 11%), decreased weight (10%)
• Uncommon (0.1% to 1%): Cryptococcal infections, Pneumocystis infections, Aspergillus infections
• Frequency not reported: Fatal/nonfatal infections (including bacterial, viral, fungal)

Fatal and nonfatal infections (including bacterial, viral, or fungal) have occurred with this drug. Grade 3 or greater infections occurred in 21% of 1476 patients with B cell malignancies who received this drug in clinical trials.

Psychiatric

• Very common (10% or more): Insomnia (up to 16%)

Renal

• Very common (10% or more): Increased blood creatinine (up to 38%)

Respiratory

• Very common (10% or more): Upper respiratory tract infection (up to 47%), cough (up to 32%), pneumonia (up to 23%), dyspnea (up to 22%), sinusitis (up to 22%), oropharyngeal pain (up to 14%), bronchitis (up to 13%), nasopharyngitis (up to 12%), influenza (up to 12%), viral upper respiratory tract infection (up to 11%)
• Common (1% to 10%): Epistaxis
• Frequency not reported: Pneumocystis jirovecii pneumonia, acute respiratory distress syndrome
• Postmarketing reports: Interstitial lung disease

Frequently asked questions

• How long can you stay on Imbruvica (ibrutinib)?
• How much does Imbruvica cost?
• Can ibrutinib be stopped safely?
• Acalabrutinib vs. ibrutinib: How do they compare?
• How quickly does Imbruvica (ibrutinib) work?
• Does ibrutinib cause hair loss?
• Is Imbruvica a chemotherapy drug?
• Who makes Imbruvica?
• What are the names of the BTK inhibitors?

Further information

Ibrutinib side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

Medical Disclaimer