Ibrutinib

Ibrutinib is a prescription medication used as an inhibitor of Bruton's tyrosine kinase (BTK) used to treat patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

Ibrutinib is available under the following different brand names: Imbruvica.

Common side effects of ibrutinib include:

• abdominal pain
• anemia
• anxiety
• bruising
• chills
• constipation
• cough
• decreased appetite
• dehydration
• diarrhea
• dizziness
• difficult breathing
• fatigue
• fever
• headache
• decreased hemoglobin levels
• bleeding
• high blood pressure (hypertension)
• increased serum creatinine, 1.5 times upper limit of normal (ULN)
• indigestion
• insomnia
• joint pain
• low platelet count
• muscle spasms
• musculoskeletal pain
• nausea
• decreased white blood cells
• nosebleed
• persistent sore throat
• numbness and tingling
• small, round spots on the skin
• platelets decreased
• pneumonia
• rash
• secondary primary malignancies
• shortness of breath
• sinus infection
• skin infections
• inflamed and sore mouth
• swelling of the extremities
• swelling of the mouth and lips
• upper respiratory tract infection
• urinary tract infection
• vomiting
• weakness

Postmarketing side effects of ibrutinib include:

• fatal bleeding events
• tumor lysis syndrome reported; use caution
• interstitial lung disease

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Adult and pediatric dosage

Capsule

• 70 mg
• 140 mg

Tablet

• 140 mg
• 280 mg
• 420 mg

Oral suspension

• 70 mg/mL

Chronic lymphocytic leukemia/small lymphocytic lymphoma

Adult dosage

• Monotherapy or in combination with rituximab or obinutuzumab, or with Bendamustine and rituximab (BR) combination: 420 mg orally once a day
• Continue until unacceptable toxicity or disease progression

Waldenström macroglobulinemia

Adult dosage

• 420 mg orally once a day
• Continue until disease progression or unacceptable toxicity

Chronic graft vs host disease

Adult dosage

• 420 mg orally once a day
• Continue until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity

Pediatric dosage

Children aged 1 to below 12 years

• 240 mg/m2 orally once a day (not to exceed 420 mg/dose)
• Daily dose if using capsules or tablets
• More than 0.7-1 m2: 210 mg
• More than 1 to 1.3 m2: 280 mg
• More than 1.3 to 1.6 m2: 350 mg
• More than 1.6 m2: 420 mg

Daily dose if using oral suspension (70 mg/mL)

• More than 0.3-0.4 m2: 1.2 mL (84 mg)
• More than 0.4-0.5 m2: 1.5 mL (105 mg)
• More than 0.5-0.6 m2: 1.9 mL (133 mg)
• More than 0.6-0.7 m2: 2.2 mL (154 mg)
• More than 0.7-0.8 m2: 2.6 mL (182 mg)
• More than 0.8-0.9 m2: 2.9 mL (203 mg)
• More than 0.9-1 m2: 3.3 mL (231 mg)
• More than 1-1.1 m2: 3.6 mL (252 mg)
• More than 1.1-1.2 m2: 4 mL (280 mg)
• More than 1.2-1.3 m2: 4.3 mL (301 mg)
• More than 1.3-1.4 m2: 4.6 mL (322 mg)
• More than 1.4-1.5 m2: 5 mL (350 mg)
• More than 1.5-1.6 m2: 5.3 mL (371 mg)
• More than 1.6 m2: 6 mL (420 mg)

Children aged 12 years and older

• 420 mg orally once a day
• Continue until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Ibrutinib has severe interactions with the following drugs:
  • adenovirus types 4 and 7 live, oral
  • BCG vaccine live
  • cholera vaccine
  • influenza virus vaccine quadrivalent, intranasal
  • measles (rubeola) vaccine
  • measles mumps and rubella vaccine, live
  • measles, mumps, rubella, and varicella vaccine, live
  • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
  • rotavirus oral vaccine, live
  • rubella vaccine
  • smallpox (vaccinia) vaccine, live
  • typhoid polysaccharide vaccine
  • typhoid vaccine live
  • varicella virus vaccine live
  • yellow fever vaccine
  • zoster vaccine live
• Ibrutinib has serious interactions with at least 76 other drugs
• Ibrutinib has moderate interactions with at least 141 other drugs
• Ibrutinib has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • drospirenone
  • larotrectinib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ibrutinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ibrutinib?”

Cautions

• Fatal and nonfatal infections (eg, bacterial, viral, or fungal) were reported; 24% of patients had a Grade greater than or equal to 3; consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections; cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with this medication; monitor and evaluate for fever and infections; treat appropriately
• Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (13-29%), thrombocytopenia (5-17%), and anemia (0-13%) occurred in patients with B-cell malignancies treated with Ibrutinib monotherapy; monitor CBC monthly
• Fatal and serious cases of renal failure occurred; treatment-emergent increases in creatinine levels up to 1.5 x ULN occurred in 67% (MCL) and 23% (CLL) and from 1.5-3x ULN in 9% (MCL) and 4% (CLL); periodically monitor creatinine and maintain hydration
• Other malignancies (10%), including non-skin carcinomas the 1,476 patients with B-cell malignancies who received therapy in clinical trials; the most frequent second primary malignancy was non-melanoma skin cancer (6%)
• Hypertension (12% of any grade) reported with a median time to onset of 5.9 months; monitor for new onset hypertension or hypertension that is not adequately controlled after initiating Ibrutinib; monitor blood pressure in patients receiving therapy; initiate or adjust anti-hypertensive medication throughout treatment as appropriate, and follow dosage modification guidelines for Grade 3 or higher hypertension
• Tumor lysis syndrome is infrequently reported; assess the baseline risk (eg, high tumor burden) and take appropriate precautions; treat as appropriate
• Based on findings in animals, can cause fetal harm when administered to a pregnant woman (see Pregnancy)
• Metabolized in the liver; although no clinical trials have been completed in patients with impaired hepatic function, Ibrutinib systemic exposure was approximately 6-fold higher in patients (N=3) with moderate hepatic impairment (Child-Pugh B) compared to healthy volunteers
• Safety has not been evaluated in patients with mild to severe hepatic impairment by Child-Pugh criteria; reduce the recommended dose when administering to patients with mild or moderate hepatic impairment (Child-Pugh class A and B); monitor patients more frequently for adverse reactions
• Cardiac arrhythmias
  • Fatal and serious cardiac arrhythmias occurred; Grade greater than 3 ventricular tachyarrhythmias occurred in 0.2% of patients
  • Deaths due to cardiac causes or sudden deaths reported, including in patients with and without pre-existing hypertension or cardiac comorbidities; patients with cardiac comorbidities may be at greater risk of these events
  • Atrial fibrillation and flutter (4%) were reported, particularly in patients with cardiac risk factors, including hypertension and diabetes mellitus, a previous history of cardiac arrhythmias, and patients with acute infections
  • At baseline and then periodically, monitor patients clinically for cardiac arrhythmias and cardiac failure; obtain an ECG for patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness, syncope, chest pain) or new-onset dyspnea, or other cardiovascular concerns
  • Manage cardiac arrhythmias and cardiac failure appropriately, and if it persists, consider the risks and benefits of treatment, and follow dose modification guidelines
• Hemorrhage
  • Grade greater than or equal to 3 bleeding events (eg, subdural hematoma, GI bleeding, haematuria) occur in up to 6%; bleeding events of any grade, including bruising and Petechiae, occurred in approximately 50% of patients treated
  • The mechanism for the bleeding events is not well understood
  • Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies
  • Consider the benefit-risk of withholding Ibrutinib for at least 3-7 days pre-surgery and post-surgery depending upon surgery type and bleeding risk
• Drug interactions overview
• Also, see Drug Modifications
  • Coadministration with a strong or moderate CYP3A inhibitor may increase Ibrutinib plasma concentrations and drug-related toxicities
  • Dose modifications are recommended when coadministered with posaconazole, voriconazole, and moderate CYP3A inhibitors
  • Coadministration with strong CYP3A inducers may decrease Ibrutinib concentrations
  • Avoid grapefruit and Seville oranges during treatment, as these contain moderate CYP3A4 inhibitors

Pregnancy and Lactation

• There are no available data on use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage; can cause fetal harm based on findings from animal studies; advise pregnant women of the potential risk to the fetus
• Pregnancy testing
  • Conduct pregnancy testing in women of reproductive potential before initiating therapy
• Contraception
  • Females: Use effective contraception during treatment and for 1 month after the last dose
  • Males: Advise men with women partners of reproductive potential to use effective contraception during treatment and for 1 month following the last dose
• Lactation
  • No information regarding the presence of Ibrutinib or its metabolites in human milk, the effects on the breastfed infant, or its effects on milk production; because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 1 week after last dose