Olarigen 150 mg (Olaparib)

Description

COMPOSITION
Olarigen 150 Tablet: Each film coated tablet contains Olaparib INN 150 mg.
CLINICAL PHARMACOLOGY
Mechanism of Action
Olaparib (Olarigen) is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2,
and PARP3. PARP enzymes are involved in normal cellular functions, such as DNA transcription and DNA repair.
Olaparib (Olarigen) has been shown to inhibit growth of select tumor cell lines in vitro and decrease tumor growth
in mouse xenograft models of human cancer, both as monotherapy or following platinum-based chemotherapy.
Increased cytotoxicity and anti-tumor activity following treatment with Olaparib (Olarigen) were noted in cell lines
and mouse tumor models with deficiencies in BRCA and non-BRCA proteins involved in the homologous
recombination repair (HRR) of DNA damage and correlated with platinum response. In vitro studies have shown
that Olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of
PARP-DNA complexes, resulting in DNA damage and cancer cell death.
Pharmacokinetics
Absorption: Following oral administration of Olaparib (Olarigen), absorption is rapid with median peak plasma
concentrations typically achieved 1.5 hours after dosing. An AUC mean accumulation ratio of 1.8 is observed at
steady state following multiple dosing of 300 mg tablets twice daily. Systemic exposure (single dose AUC) to
Olaparib (Olarigen) increases approximately proportionally with doses over the dose range of 25 mg to 450 mg,
Cmax increased slightly less than proportionally for the same dose range. Co-administration of a high fat meal
with Olaparib (Olarigen) slowed the rate (tmax delayed by 2.5 hours) of absorption, but did not significantly alter
the extent of Olaparib (Olarigen) absorption (mean AUC increased by approximately 8%).
Distribution: Olaparib (Olarigen) had a mean (± standard deviation) apparent volume of distribution of 158 ±
136 L after a single 300 mg dose of Olaparib (Olarigen). The in vitro protein binding of Olaparib (Olarigen) is
approximately 82%.
Metabolism: In vitro, CYP3A4/5 were shown to be the enzymes primarily responsible for the metabolism of
Olaparib (Olarigen). Following oral dosing of 14C-Olaparib (Olarigen) to female patients, unchanged Olaparib
(Olarigen) accounted for the majority of the circulating radioactivity in plasma (70%). It was extensively
metabolized with unchanged drug accounting for 15% and 6% of radioactivity in urine and feces, respectively.
The majority of the metabolism is attributable to oxidation reactions with a number of the components produced
undergoing subsequent glucuronide or sulfate conjugation.
Excretion: A mean (± standard deviation) terminal plasma half-life of 14.9 ± 8.2 hours and apparent plasma
clearance of 7.4 ± 3.9 L/h were observed after a single 300 mg dose of Olaparib (Olarigen). Following a single
dose of 14C-Olaparib, 86% of the dosed radioactivity was recovered within a 7-day collection period, 44% via the
urine and 42% via the feces. The majority of the material was excreted as metabolites.
INDICATIONS
First-Line Maintenance Treatment of BRCA-mutated Advanced Ovarian Cancer:
Olaparib (Olarigen) is indicated for the maintenance treatment of adult patients with deleterious or suspected
deleterious germline or somatic BRCA-mutated (gBRCAmor sBRCAm) advanced epithelial ovarian, fallopian
tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based
chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Olaparib
(Olarigen).