Drug Interactions
PARP inhibitors can have significant interactions with other drug classes depending on their unique pharmacological properties. The specific interactions for each PARP inhibitor are listed in the table below [1-8].
Table 4: Drug interactions that can occur with PARP inhibitors and their management[1-8]
Agent |
Pharmacology |
Interaction Management |
Examples |
|---|---|---|---|
Olaparib |
Metabolised by CYP3A4; induces CYP3A and CYP2B6 and inhibits CYP3A |
Avoid potent CYP3A inhibitors; if they must be used, reduce olaparib dose. Avoid potent CYP3A inducers; if they need to be used be aware that efficacy of olaparib may be reduced. |
Antibiotics (clarithromycin, erythromycin, rifampicin, rifabutin) Anti(retro)-virals (indinavir, saquinavir, boceprevir, ritonavir, cobicistat, nevirapine) Antifungals (itraconazole, fluconazole) Cardiovascular medication (diltiazem, verapamil) Antiepileptics (phenytoin, carbamazepine) Foods and herbs (grapefruit, starfruit, bitter oranges, St John’s wort) |
Rucaparib |
Metabolised by CYP2D6 (and to a lesser extent by CYP1A2 and CYP3A4) |
Caution with potent CYP3A4/5 inducers or inhibitors with a narrow therapeutic index |
Caution with CYP3A substrates such as alfentanil, astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, terfenadine. |
Talazoparib |
Minimal hepatic metabolism. Substrate of P-gpand BCRP transporters |
Avoid P-gp inhibitors and BCRP inhibitors (monitor if BCRP inhibitors cannot be avoided; reduce dose with certain P-gp inhibitors) |
Antibiotics (clarithromycin) Antifungals (itraconazole) Cardiovascular medication (amiodarone carvedilol, verapamil) Oncology medications (gefitinib, imatinib) |
Niraparib |
Metabolised primarily by carboxylesterases |
No known interactions with major CYP enzymes or transporters; weak inhibitor of BCRP; weakly induces CYP1A2 in vitro |
BCRP, breast cancer resistance protein; CYP, cytochrome; P-gp, p-glycoprotein
References
- AstraZeneca. LYNPARZA® (olaparib) tablets for oral use. 2018.
- European Medicines Agency. Olaparib Summary of Product Characteristics. 2019.
- Clovis Oncology. RUBRACA® (rucaparib) tablets, for oral use. 2018.
- European Medicines Agency. Rucaparib Summary of Product Characteristics. 2018
- Tesaro. ZEJULA® (niraparib) capsules, for oral use [prescribing information]. 2018.
- Pfizer. TALZENNA™ (talazoparib) capsules, for oral use [prescribing information]. New York, NY: Pfizer Inc,2018.
- Friedlander M, Banerjee S, Mileshkin L et al. Practical guidance on the use of olaparib capsules as maintenance therapy for women with BRCA mutations and platinum-sensitive recurrent ovarian cancer. Asia Pac J Clin Oncol 2016; 12: 323-331.
- LaFargue CJ, Dal Molin GZ, Sood AK, Coleman RL. Exploring and comparing adverse events between PARP inhibitors. Lancet Oncol 2019; 20: e15-e28.