Olarigen

Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3. PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair. Olaparib 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 were noted in cell lines and mouse tumor models with deficiencies in BRCA. In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, resulting in disruption of cellular homeostasis and cell death.

Clinical studies of olaparib in combination with other anti-cancer agents, including DNA damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity. The recommended Olaparib monotherapy dose is not suitable for combination with myelosuppressive anti-cancer agents. Olaparib is predominantly metabolised by CYP3A. Co-administered CYP3A inhibitors or inducers may respectively increase or decrease olaparib plasma concentration.

The most common serious adverse reaction reported was anemia (2.4% olaparib vs 2.2% chemotherapy). The following serious ADRs were reported in one patient each: dermatitis allergic, neutrophil count decreased and platelet count decreased. The proportion of patients who permanently discontinued Olaparib due to adverse events was 4.9% in the Olaparib arm compared with 7.7% in the chemotherapy arm. Anemia and platelet count decrease were the only adverse reactions leading to discontinuation of Olaparib in more than one patient.

Pregnancy: Olaparib can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. Olaparib wasteratogenic and caused embryo-fetal toxicity in rats at exposures below those in patients receiving the recommended human dose of 400 mg twice daily. If this drug is used during pregnancy, or if a patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for loss of the pregnancy.

Nursing Mothers: It is not known whether olaparib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from olaparib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): occurred in patients exposed to Olaparib, and the majority of reports were fatal. Monitor patients for hematological toxicity at baseline and monthly thereafter. Discontinue if MDS/AML is confirmed.

Pneumonitis: occurred in patients exposed to Olaparib, and some cases were fatal. Interrupt treatment if pneumonitis is suspected. Discontinue if pneumonitis is confirmed.

Embryo-Fetal Toxicity: Olaparib can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception

Pediatric Use: The safety and efficacy of Olaparib has not been established in pediatric patients.

Targeted Cancer Therapy

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

Store in a dry place below 30°C, protect from light. Keep out of the reach of children.