Olaparib

Olaparib is a poly-ADP glycan polymerase (PARP) inhibitor approved by the FDA on December 19, 2014 for advanced ovarian cancer and HER2- metastatic breast cancer harboring BRCA mutations after at least three prior treatments of chemotherapy.

Olaparib has been approved by the United States FDA for the treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer with deleterious or suspected deleterious BRCA gene mutations who have demonstrated a complete or partial response after first-line platinum-based chemotherapy

1. Main ingredient

Olaparib

2. Applicable people

Adult patients with epithelial ovarian, fallopian tube, or primary peritoneal and prostate cancer

3. Use in Specific Populations

3.1 Pregnancy  

Based on findings in animals and its mechanism of action, Lynparza  can cause fetal harm when administered to a pregnant woman. There are no available data on Lynparza  use in pregnant women to inform the drug associated risk. In an animal reproduction study, the  administration of olaparib to pregnant rats during the period of organogenesis caused teratogenicity and  embryo-fetal toxicity at exposures below those in patients receiving the recommended human dose of 300  mg twice daily. Apprise pregnant women of the potential hazard to the fetus and the potential  risk for loss of the pregnancy.  The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 

3.2 Lactation  

No data are available regarding the presence of olaparib in human milk, or on its effects on the breastfed  infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infants  from Lynparza, advise a lactating woman not to breastfeed during treatment with Lynparza and for one  month after receiving the last dose.

3.3 Females and Males of Reproductive Potential  

Pregnancy Testing  

Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with  Lynparza.  Contraception  Females  Lynparza can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with  Lynparza and for at least 6 months following the last dose.

3.4 Pediatric Use  

The safety and efficacy of Lynparza have not been established in pediatric patients.  

3.5 Geriatric Use  

In clinical studies of Lynparza enrolling 482 patients with advanced solid tumors who received Lynparza  tablets 300 mg twice daily as monotherapy, 135 (28%) patients were aged ≥65 years. There appeared to  be no major difference in the safety profile of patients treated with olaparib aged <65 years versus ≥65  years, nor within the age categories of 65 to 74 years, 75 to 84 years. No patients were aged ≥85 years.

3.6 Hepatic Impairment  

No adjustment to the starting dose is required in patients with mild hepatic impairment. A 15% increase  in mean exposure (AUC) was observed in patients with mild hepatic impairment (based on Child-Pugh  classification A) compared to patients with normal hepatic function. There are no data in patients with  moderate or severe hepatic impairment.

3.7 Renal Impairment  

No adjustment to the starting dose is required in patients with mild renal impairment, but patients should  be monitored closely for toxicity. A 24% increase in mean exposure (AUC) was observed in patients with  mild renal impairment (CLcr = 51-80 mL/min) compared to patients with normal renal function (CLcr>80 mL/min). A 44% increase in AUC was observed in patients with moderate renal impairment  (CLcr 31-50 mL/min) compared to patients with normal renal function (CLcr >80 mL/min). For patients  with moderate renal impairment, reduce the dose of Lynparza to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage disease  (CLcr ≤30 mL/min).

4. Over dosage

There is no specific treatment in the event of Lynparza overdose, and symptoms of overdose are not  established. In the event of an overdose, physicians should follow general supportive measures and should  treat the patient symptomatically.

5. Storage

Store at 20ºC to 25ºC (68°F to 77°F), excursions permitted to 15ºC to 30ºC (59ºF to 86ºF). Store in original bottle to protect from moisture.

6. Pharmacokinetics

Following oral administration of olaparib, 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 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 slowed the rate (tmax delayed by 2.5 hours) of  absorption, but did not significantly alter the extent of olaparib absorption (mean AUC increased by  approximately 8%).

FDA,2021.08