Indications
Olaparib is used on its own (as monotherapy) for adults with metastatic breast cancer that is HER2-negative (human epidermal growth factor receptor 2-negative) and carries a deleterious or suspected deleterious germline BRCA mutation (gBRCAm). These patients must already have been treated with chemotherapy, either in the neoadjuvant, adjuvant or metastatic setting. If the cancer is hormone receptor (HR)-positive, the patient should have progressed on endocrine therapy or be considered unsuitable for it. The germline BRCA mutation must be confirmed before treatment with Olaparib begins. For ovarian cancer, it is also used as monotherapy, as maintenance treatment in adults with platinum sensitive relapsed (PSR) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer. This applies to patients who are in response (complete response or partial response) to platinum-based chemotherapy.
⚠️ Always consult a registered physician before taking any medicine.
Pharmacology
Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2 and PARP3. These enzymes take part in normal cell functions such as DNA transcription, cell cycle regulation and DNA repair. In laboratory studies, olaparib slowed the growth of some tumour cell lines. It also decreased tumour growth in mouse xenograft models of human cancer, both as monotherapy and following platinum-based chemotherapy. Cytotoxicity and anti-tumour activity were greater in cell lines and mouse tumour models with deficiencies in BRCA. In vitro studies have shown that the cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, which disrupts cellular homeostasis and leads to cell death.
Absorption: When olaparib is taken by mouth as the capsule, it is absorbed quickly, and peak plasma concentrations are usually reached 1 to 3 hours after the dose. With repeated dosing there is no marked accumulation (accumulation ratio of 1.4 to 1.5 for twice daily dosing), and steady state exposure is reached within 3 to 4 days. Limited data suggest that systemic exposure (AUC) rises less than proportionally with dose over the range of 100 to 400 mg, though the PK data varied across trials. A high fat meal slowed the rate of absorption (Tmax delayed by 2 hours) but did not significantly change how much was absorbed (mean AUC increased by approximately 20%).
Distribution: After a single 400 mg dose, the mean (± standard deviation) apparent volume of distribution at steady state was 167 ± 196 L. In vitro protein binding is approximately 82%.
Metabolism: In vitro, CYP3A4/5 were shown to be the enzymes mainly responsible for metabolising olaparib. In female patients given oral 14C-olaparib, unchanged drug made up most of the circulating radioactivity in plasma (70%). The drug was extensively metabolised, and unchanged drug accounted for 15% of radioactivity in urine and 6% in faeces. Most of the metabolism is by oxidation, and a number of the products then go on to glucuronide or sulfate conjugation.
Excretion: After a single 400 mg dose, the mean (± standard deviation) terminal plasma half-life was 11.9 ± 4.8 hours and the apparent plasma clearance was 8.6 ± 7.1 L/h. After a single dose of 14C-olaparib, 86% of the radioactivity was recovered within a 7-day collection period, 44% in urine and 42% in faeces. Most of it was excreted as metabolites.
Pregnancy & Breastfeeding
Pregnancy
Olaparib can harm an unborn baby when given to a pregnant woman. This is based on how the medicine works and on what was seen in animals. In rats, olaparib was teratogenic and caused toxicity to the embryo and fetus at exposures below those in patients taking the recommended human dose of 400 mg twice daily. If olaparib is used during pregnancy, or if a patient becomes pregnant while taking it, she should be told about the possible danger to the baby and the possible risk of losing the pregnancy.
Nursing mothers
It is not known whether olaparib passes into human milk. Many drugs do pass into breast milk, and olaparib could cause serious side effects in a nursing baby. So a decision has to be made either to stop nursing or to stop the medicine, taking into account how important the medicine is for the mother.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Dosage Reference
⚠️ Reference ranges from official sources only. Consult your doctor for personalized dosing.
Side Effects & Interactions
Side Effects
No side-effect data recorded yet.