Lynparza

Olaparib

Monotherapy & in combination w/ bevacizumab for maintenance treatment of adults w/ advanced high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer in response to 1st-line platinum-based chemotherapy. Monotherapy for maintenance treatment of adults w/ platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer; germline BRCA-mutated metastatic adenocarcinoma of the pancreas. Monotherapy for adults w/ germline BRCA1/2-mutations, who have HER2 -ve locally advanced or metastatic breast cancer; metastatic castration-resistant prostate cancer & homologous recombination repair gene mutations.

300 mg (two 150 mg tab) bid. Total daily dose: 600 mg. May be reduced to 250 mg (one 150 mg tab & one 100 mg tab) bid (total daily dose of 500 mg). May further reduce to 200 mg (two 100 mg tab) bid (total daily dose of 400 mg). Duration of treatment: Continue until progression of underlying disease or unacceptable toxicity. Patients w/ platinum-sensitive relapsed (PSR) high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy Start treatment no later than 8 wk after completion of final dose of the platinum-containing regimen. Treatment duration: Monotherapy maintenance treatment of newly diagnosed advanced BRCA-mutated ovarian cancer Continue treatment until radiological disease progression, unacceptable toxicity or for up to 2 yr if there is no radiological evidence of disease after 2 yr of treatment. Maintenance treatment of newly diagnosed advanced ovarian cancer in combination w/ bevacizumab Continue treatment for 2 yr or until disease progression. May continue beyond 2 yr in patients w/ evidence of disease at 2 yr. Co-administration w/ CYP3A inhibitors Reduce dose to 100 mg bid (total daily dose: 200 mg) w/ strong CYP3A4 inhibitor or 150 mg bid (total daily dose: 300 mg) w/ moderate CYP3A4 inhibitor. Moderate renal impairment (CrCl 31-50 mL/min) 200 mg (two 100 mg tab) bid. Total daily dose: 400 mg.

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 if myelodysplastic syndrome/AML; pneumonitis is confirmed. Interrupt treatment if severe haematological toxicity or blood transfusion dependence develops; in patient presenting w/ new or worsening resp symptoms eg, dyspnoea, cough & fever or abnormal chest radiologic finding. Not to start treatment until patient has recovered from haematological toxicity caused by previous anticancer therapy. Perform baseline testing, followed by mthly monitoring of CBC for 1st 12 mth of treatment & periodically thereafter; bone marrow analysis &/or blood cytogenetic analysis if blood parameters remain clinically abnormal after 4 wk of dose interruption. Not recommended for co-administration w/ strong or moderate CYP3A inhibitors & inducers. Moderate influence on the 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 2 forms of reliable contraception prior to, during therapy & for 1 mth after receiving the last dose; perform pregnancy test prior to & regularly during treatment. Male patients w/ partners who are pregnant or of childbearing potential should use reliable contraception & should not donate sperm during therapy & for 3 mth after receiving the last dose. Not to be used during pregnancy. Childn & adolescents.

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

Potentiation & prolongation of myelosuppressive toxicity w/ other anti-cancer medicinal products including DNA damaging agents. Coadministration 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. Concomitant use w/ grapefruit juice; moderate to strong CYP3A inducers eg, efavirenz, rifabutin; sensitive CYP3A substrates or substrates w/ narrow therapeutic margin eg, simvastastin, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, sirolimus, tacrolimus & quetiapine; P-gp substrates eg, simvastatin, pravastatin, dabigatran, digoxin & colchicine. Decreased C_max & AUC w/ strong CYP3A inducers eg, phenytoin, rifampicin, rifapentine, carbamazepine, nevirapine, phenobarb & St. John's wort. Reduced exposure to substrates of CYP2C9, CYP2C19 & P-gp. Reduced efficacy of hormonal contraceptives. Increased exposure to BCRP substrates (eg, MTX, rosuvastatin), OATP1B1 (eg, bosentan, glibenclamide, repaglinide, statins & valsartan), OCT1 (eg, metformin), OCT2 (eg, serum creatinine), OAT3 (eg, furosemide & MTX), MATE1 & MATE2K (eg, metformin). Decreased exposure w/ tamoxifen.

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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