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
Therapeutic class
Targeted Cancer 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.
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
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
Contraindications
Contraindications:
- Hypersensitivity
- Concomitant use with St. John's wort-containing preparations
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.
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.
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.
Storage conditions
Store in a dry place below 30°C, protect from light; keep out of reach of children.
Chemical structure
Ibrutinib