OLAPARIB
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OLAPARIB (OLAPARIB).
Poly (ADP-ribose) polymerase (PARP) inhibitor that blocks base excision repair, leading to accumulation of DNA double-strand breaks and cell death in tumors with homologous recombination repair deficiency.
| Metabolism | Primarily metabolized by CYP3A4/5; minor contribution from CYP2C8. |
| Excretion | Fecal (84%), renal (6%) as unchanged drug; <1% in urine as metabolites |
| Half-life | Terminal half-life ~11-12 hours; steady-state reached by day 3-5; supports BID dosing |
| Protein binding | 82% bound to plasma proteins (primarily albumin) |
| Volume of Distribution | Vd/F ~158 L (~2.2 L/kg for 70 kg); extensive tissue distribution |
| Bioavailability | Oral: ~80% (fasting); food reduces absorption but not clinically significant |
| Onset of Action | Oral: Clinical effect (PARP inhibition) within hours; tumor response may take weeks to months |
| Duration of Action | Duration of PARP inhibition ~24 hours post-dose; clinical effect sustained with continuous BID dosing |
300 mg orally twice daily, taken with or without food. For patients with BRCA-mutated advanced ovarian cancer after ≥3 prior lines of chemotherapy; or as maintenance therapy after platinum-based chemotherapy for recurrent ovarian cancer; or for HER2-negative metastatic breast cancer with germline BRCA mutation; or for metastatic pancreatic adenocarcinoma with germline BRCA mutation after first-line platinum-based chemotherapy; or for metastatic castration-resistant prostate cancer with HRR gene mutations.
| Dosage form | TABLET |
| Renal impairment | For CrCl 31-50 mL/min: 200 mg orally twice daily. For CrCl <30 mL/min: not recommended (no data). No dose adjustment required for CrCl >50 mL/min. |
| Liver impairment | Child-Pugh Class A (mild): 300 mg orally twice daily. Child-Pugh Class B (moderate): 200 mg orally twice daily. Child-Pugh Class C (severe): not recommended (no data). |
| Pediatric use | Safety and efficacy not established in pediatric patients. No recommended dose. |
| Geriatric use | No specific dose adjustment based on age alone. Clinical trials included patients ≥65 years, with no overall differences in efficacy or safety; however, monitor for increased risk of myelodysplastic syndrome/acute myeloid leukemia and renal function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OLAPARIB (OLAPARIB).
| Breastfeeding | No data are available on the presence of olaparib in human milk, its effects on the breastfed infant, or its effects on milk production. Because of the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed during treatment with olaparib and for 1 month after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | Based on animal studies and its mechanism of action (PARP inhibition), olaparib is expected to cause fetal harm. There are no adequate and well-controlled studies in pregnant women. Olaparib should not be used during pregnancy. If used, advise the patient of the potential risk to the fetus. Specifically, in animal reproduction studies, olaparib caused teratogenicity (including skeletal abnormalities and embryofetal death) at maternal exposures below the recommended human dose. The risk is present throughout all trimesters due to continuous fetal development and DNA repair processes. |
■ FDA Black Box Warning
No FDA-mandated black box warning exists.
| Serious Effects |
["Known hypersensitivity to olaparib or any of its excipients","Concurrent use with strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, St. John's wort)","Breastfeeding","Pregnancy (based on mechanism of action and animal data)"]
| Precautions | ["Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) have been reported, particularly with prolonged exposure","Pneumonitis including interstitial lung disease","Embryo-fetal toxicity; advise females of reproductive potential to use effective contraception","Venous thromboembolic events","Hypertension","Fatigue, nausea, anemia, and other hematologic toxicities","Potential for drug interactions with strong/moderate CYP3A4 inhibitors or inducers"] |
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| Fetal Monitoring | If olaparib is used during pregnancy, or if the patient becomes pregnant while taking olaparib, apprise the patient of the potential hazard to the fetus. Monitor for fetal growth and development via ultrasound. Additionally, monitor maternal complete blood counts due to risk of myelodysplastic syndrome/acute myeloid leukemia and hematologic toxicity. Also monitor renal function and liver function tests as per standard olaparib monitoring. |
| Fertility Effects | Based on animal studies, olaparib may impair male and female fertility. In female rats, olaparib caused disruption of the estrous cycle and reduced fertility. In male dogs and rats, olaparib caused testicular degeneration, reduced sperm count, and altered sperm morphology. The effect on human fertility is unknown but potential for reversible impairment exists. |