Generic
Ibrutinib
7 brands available in the market
At a glance
Ibrutinib is a kinase inhibitor used for the treatment of Mantle Cell Lymphoma (MCL), Chronic Lymphocytic Leukemia (CLL), CLL with 17p deletion, Waldenström's Macroglobulinemia (WM), and Marginal Zone Lymphoma (MZL).
Description
Ibrutinib is a small-molecule BTK inhibitor that inhibits BTK enzymatic activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. BTK's role in signaling through B-cell surface receptors results in activation of pathways necessary for B-cell trafficking, chemotaxis, and adhesion. Ibrutinib inhibits malignant B-cell proliferation and survival.
Indications
- Mantle Cell Lymphoma (MCL) - who have received at least one prior therapy
- Chronic Lymphocytic Leukemia (CLL) - who have received at least one prior therapy
- Chronic Lymphocytic Leukemia with 17p deletion
- Waldenström's Macroglobulinemia (WM)
- Marginal Zone Lymphoma (MZL) - who require systemic therapy and have received at least one prior anti-CD20-based therapy
Pharmacological class
BTK Inhibitor (Kinase Inhibitor)
Pharmacology
Ibrutinib is a small-molecule inhibitor of BTK. It forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. BTK's role in signaling through the B-cell surface receptors results in activation of pathways necessary for B-cell trafficking, chemotaxis, and adhesion. Ibrutinib inhibits malignant B-cell proliferation and survival in vivo.
Mechanism of action
Forms a covalent bond with BTK active site to inhibit BTK activity, blocking B-cell receptor signaling pathways and reducing malignant B-cell proliferation and survival.
Dosage
Adult Dose (Oral):
- Mantle Cell Lymphoma (MCL) & Marginal Zone Lymphoma (MZL): 560 mg (four 140 mg capsules) once daily
- Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) & Waldenström Macroglobulinemia (WM): 420 mg (three 140 mg capsules) once daily
- CLL (in combination with bendamustine and rituximab): 420 mg once daily
Hepatic Impairment: Mild (Child Pugh Class A): 140 mg once daily; Moderate-to-severe (Classes B and C): Avoid use
Child Dose: Safety and efficacy not established
Administration
Administer orally once daily at approximately the same time each day; swallow capsules whole with water; do not open, break, or chew capsules.
Missed dose
If you miss a dose, take it as soon as possible; if it is almost time for your next dose, skip the missed dose and go back to regular schedule; do not double the dose.
Drug interactions
Drug Interactions:
- Increased exposure with strong or moderate CYP3A4 inhibitors (avoid; reduce dose if necessary)
- Decreased exposure with strong CYP3A4 inducers (avoid)
- Avoid grapefruit and Seville oranges (moderate CYP3A4 inhibitors)
- Decreased exposure with drugs increasing stomach pH (PPIs)
- Digoxin or methotrexate should be taken at least 6 hours before or after treatment
Food interactions
Food Interactions: Avoid grapefruit and Seville oranges as they contain moderate inhibitors of CYP3A4.
Contraindications
Contraindications:
- Hypersensitivity
- Concomitant use with St. John's wort-containing preparations
Side effects
Most Common (>10%):
- Diarrhea (51-63%)
- Bruising (30-54%)
- Fatigue (31-41%)
- Nausea (21-31%)
- Rash (25-27%)
- Musculoskeletal pain (27-37%)
- Headache (13-19%)
- Dizziness (14-21%)
- Upper respiratory tract infection (34-48%)
- Hemorrhage (48%)
- Neutropenia (27-29%)
- Thrombocytopenia (10-17%)
Serious: Hemorrhage, Infections, Cytopenias, Atrial Fibrillation, Hypertension, Second Primary Malignancies, Tumor Lysis Syndrome
Use in pregnancy
Use in Pregnancy: Ibrutinib can cause fetal harm; animal studies showed embryofetal toxicity including malformations; if used during pregnancy or patient becomes pregnant, apprise of potential risk to fetus.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: No information regarding presence of Ibrutinib or its metabolites in human milk, effects on breastfed infant, or effects on milk production.
Precautions & warnings
Precautions:
- Monitor for bleeding
- Monitor patients for fever and infections and evaluate promptly
- Complete blood counts should be checked monthly
- Monitor for atrial fibrillation
- Second primary malignancies (including skin cancers) have occurred
- Monitor patients at risk for Tumor Lysis Syndrome (TLS)
- Embryo-Fetal Toxicity: Can cause fetal harm; advise women to avoid pregnancy
Pediatric use
Safety and efficacy in pediatric patients have not been established.
Geriatric use
In clinical studies, 62% were ≥65 years, 21% were ≥75 years; no overall effectiveness differences; anemia and Grade 3+ pneumonia occurred more frequently among older patients.
Renal / hepatic impairment
Renal Impairment: No specific data; caution advised.
Hepatic Impairment: Metabolized in liver; exposure increased in hepatic impairment; administration not recommended in moderate or severe hepatic impairment; monitor for signs of toxicity.
Overdose effects
Overdose: No specific experience in management of overdose; one healthy subject experienced reversible Grade 4 hepatic enzyme increases (AST and ALT) after 1680 mg dose; closely monitor patients who ingest more than recommended dosage and provide appropriate supportive treatment.
Therapeutic class
Targeted Cancer Therapy
Storage conditions
Store in a dry place below 30°C, protect from light; keep out of reach of children.
Chemical structure
Ibrutinib