Lynparza

Olaparib

Ovarian cancer: Monotherapy for maintenance treatment of adults w/ advanced (FIGO stages III & IV) BRCA1/2-mutated (germline &/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response following completion of 1st-line platinum-based chemotherapy; w/ platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In combination w/ bevacizumab for maintenance treatment of adults w/ advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to 1st-line platinum-based chemotherapy & whose cancer is associated w/ homologous recombination deficiency (HRD) +ve status defined by either deleterious or suspected deleterious BRCA mutation &/or genomic instability. Breast cancer: Adjuvant treatment for adults w/ germline BRCA-mutated HER2 -ve high risk early breast cancer who have previously been treated w/ neoadjuvant or adjuvant chemotherapy. Monotherapy for adults w/ germline BRCA1/2-mutations, who have HER2 -ve metastatic breast cancer & have previously been treated w/ anthracycline & taxane in the neoadjuvant, adjuvant or metastatic setting unless unsuitable for these treatments. Patients w/ hormone receptor (HR) +ve breast cancer should also have progressed on or after prior endocrine therapy, or be considered unsuitable for endocrine therapy. Pancreatic cancer: Maintenance treatment of adults w/ deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 wk of 1st-line platinum-based chemotherapy. Prostate cancer: Monotherapy for adults w/ deleterious or suspected deleterious germline &/or somatic BRCA- or ATM-mutated metastatic castration resistant prostate cancer (mCRPC) who have progressed following prior treatment w/ new hormonal agent eg, abiraterone or enzalutamide. In combination w/ abiraterone & prednisone or prednisolone for adults w/ deleterious or suspected deleterious BRCA-mutated mCRPC.

300 mg bd, continue until underlying disease progression. Dose adjustment for AR Reduce to 250 mg bd or further reduction to 200 mg bd may be considered. Dose adjustment for co-administration w/ CYP3A inhibitor Reduce to 100 mg bd w/ strong inhibitor or 150 mg bd w/ moderate inhibitor. Moderate renal impairment (CrCl 31-50 mL/min) 200 mg bd.

May be taken with or without food: Swallow whole, do not chew/crush/dissolve/divide.

Hypersensitivity. Lactation during treatment & for 1 mth after last dose.

Discontinue use if myelodysplastic syndrome/AML; pneumonitis is confirmed. Haematological toxicity; new or worsening resp symptoms eg, dyspnoea, cough & fever or radiological abnormality. Monitor for clinical signs & symptoms of venous thrombosis & pulmonary embolism during treatment. Non-Caucasian patients. Not recommended in co-administration w/ strong or moderate CYP3A inhibitors & inducers. May affect ability to drive & use machines. Not recommended in severe renal impairment or ESRD (CrCl ≤30 mL/min) & severe hepatic impairment (Child-Pugh class C). Women of childbearing potential must use effective contraception prior to, during & for 1 mth after last dose. Male patients must use effective contraception & not donate sperm during & for 3 mth after last dose. Not to be used during pregnancy. Contraindicated during lactation & for 1 mth after last dose. Childn & adolescents.

Anaemia, neutropenia, thrombocytopenia, leukopenia; decreased appetite; dizziness, headache, dysgeusia; cough, dyspnoea; vomiting, diarrhoea, nausea, dyspepsia; fatigue, asthenia. Thrombocytopenia; lymphopenia; stomatitis, upper abdominal pain; rash; increased blood creatinine; VTE.

Potentiated & prolonged myelosuppressive toxicity w/ other anticancer medicinal products. Closely monitor patients co-administered w/ vaccines or immunosuppressants. Increased mean C_max & AUC w/ strong (eg, itraconazole, telithromycin, clarithromycin, PIs boosted w/ ritonavir or cobicistat, boceprevir, telaprevir) or moderate (eg, erythromycin, diltiazem, fluconazole, verapamil) CYP3A inhibitors; grapefruit juice. Decreased mean C_max & AUC w/ strong CYP3A inducers eg, phenytoin, rifampicin, rifapentine, carbamazepine, nevirapine, phenobarb, St. John's wort. Not recommended w/ moderate to strong CYP3A inducers eg, efavirenz, rifabutin. Clinical monitoring w/ CYP3A substrates or substrates w/ narrow therapeutic margin (eg, simvastatin, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, sirolimus, tacrolimus, quetiapine) & P-gp substrates (eg, pravastatin, dabigatran, digoxin, colchicine). Reduced exposure to CYP1A2, 2B6 & 3A4, CYP2C9, CYP2C19 & P-gp substrates. Increased exposure to BRCP, OATP1B1, OCT1, OCT2, OAT3, MATE1 & MATE2K substrates.

Targeted Cancer Therapy

L01XK01 - olaparib ; Belongs to the class of poly (ADP-ribose) polymerase (PARP) inhibitors. Used in the treatment of cancer.

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