Generic
Olaparib
15 brands available in the market
At a glance
Olaparib is a PARP inhibitor used for BRCA-mutated HER2-negative metastatic breast cancer and platinum-sensitive relapsed ovarian cancer. It inhibits PARP enzymes to disrupt DNA repair and cause cancer cell death.
Description
Olaparib is an inhibitor of PARP1, PARP2 and PARP3 enzymes. PARP enzymes are involved in DNA transcription, cell cycle regulation and DNA repair. Olaparib inhibits PARP enzymatic activity and increases PARP-DNA complex formation to disrupt cellular homeostasis and cause cell death. Increased cytotoxicity is noted in cell lines with BRCA deficiencies.
Indications
- BRCA-mutated HER2-negative metastatic breast cancer (previously treated with chemotherapy)
- Platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer (maintenance therapy)
Therapeutic class
Targeted Cancer Therapy
Pharmacological class
PARP Inhibitor
Pharmacology
Olaparib inhibits PARP1, PARP2 and PARP3 enzymes to prevent DNA repair. In BRCA-deficient cells with no alternative DNA repair pathways, olaparib causes cell death (synthetic lethality).
Mechanism of action
Causes death of BRCA-mutated cancer cells by inhibiting DNA repair.
Dosage
Adult Dose (Oral):
- Recommended dose: 400 mg (8 x 50 mg capsules) twice daily, total daily 800 mg
- May be taken with or without food
- Continue until disease progression or unacceptable toxicity
Dose Reduction: 200 mg twice daily (total 400 mg/day); further reduce to 100 mg twice daily if needed
Administration
- Swallow capsule whole; do not chew, dissolve or open
- Take at approximately the same time each day
- May be taken with or without food
Missed dose
If you miss a dose, take at next scheduled time; do not take additional dose.
Side effects
Common Serious Adverse Reactions:
- Anemia
- Allergic dermatitis
- Decreased neutrophil count
- Decreased platelet count
- Thrombocytopenia
Precautions & warnings
- Risk of MDS/AML (<1.5%); discontinue if confirmed
- Do not start until recovery from hematological toxicity from previous chemotherapy (≤ Grade 1)
- Monitor CBC regularly
- Pneumonitis (<1%); discontinue if confirmed
- Can cause fetal harm; use effective contraception
Contraindications
- Hypersensitivity
Drug interactions
- Strong CYP3A inhibitors (itraconazole, clarithromycin, ketoconazole) increase olaparib AUC by 170%; reduce dose to 150 mg twice daily
- Moderate CYP3A inhibitors (fluconazole) increase AUC by 121%; reduce dose to 200 mg twice daily
- Strong CYP3A inducers (rifampicin) decrease AUC by 87%; avoid
- Avoid grapefruit, grapefruit juice, Seville oranges
Food interactions
May be taken with or without food; high-fat meal increases AUC by approximately 20%.
Use in pregnancy
Use in Pregnancy: Olaparib is highly unsafe during pregnancy; teratogenic and embryo-fetal toxicity seen in animal studies. Do not use.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Unknown if excreted in human milk; discontinue nursing or discontinue drug.
Pediatric use
Safety and efficacy not established in pediatric patients.
Geriatric use
Elderly may require dose adjustment.
Renal / hepatic impairment
Renal Impairment: Mild (ClCr 51-80): No dose adjustment; Moderate (ClCr 31-50): 300 mg twice daily; Severe (ClCr ≤30): Not studied.
Hepatic Impairment: Caution in liver disease; dose adjustment may be needed.
Overdose effects
No specific treatment for overdose; symptomatic supportive measures.
Storage conditions
Store in a dry place below 30°C, protect from light; keep out of reach of children.
Chemical structure
Olaparib