Product Information
Registration Status: ActiveLYNPARZA FILM-COATED TABLET 100MG is approved to be sold in Singapore with effective from 2019-04-09. It is marketed by ASTRAZENECA SINGAPORE PTE LTD, with the registration number of SIN15663P.
This product contains Olaparib 100mg in the form of TABLET, FILM COATED. It is approved for ORAL use.
This product is manufactured by AbbVie Deutschland GmbH & Co. KG in PUERTO RICO,AbbVie Ltd in GERMANY, andAstraZeneca UK Limited (Primary packager and Secondary packager) in UNITED KINGDOM.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
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. Olaparib is available as oral tablets marketed under the brand name Lynparza and was initially indicated as a maintenance therapy or monotherapy for the treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer. On January 12, 2018, FDA expanded the approved use of Lynparza to include chemotherapy-experienced patients with germline breast cancer susceptibility gene (BRCA) mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. In a randomized clinical trial involving patients with HER2-negative metastatic breast cancer with a germline BRCA mutation, the median progression-free survival for patients taking Lynparza was 7 months compared to 4.2 months for patients taking chemotherapy only. Patient selection for this newly-approved indication can be performed based on an FDA-approved genetic test, called the BRACAnalysis CDx.
Indication
* Indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. * Indicated as monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated (as detected by an FDA-approved test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. * Indicated for the treatment of patients with germline breast cancer susceptibility gene (BRCA) mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, who have been previously treated with chemotherapy.
Mechanism of Action
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.
Pharmacokinetics
- Absorption
- Peak plasma concentrations achieved typically between 1 to 3 hours following oral administration of olaparib in capsule formulation.
- Distribution
- 167 +/-196 L following a single dose of 400mg olaparib.
- Metabolism
- Primarily CYP3A4 in vitro.
- Elimination
Clearance
8.6 +/- 7.1L/h.
Toxicity
The most commonly reported side effects reported during clinical trials included cough, constipation, dysguesia, peripheral deem, back pain, dizziness, headache, urinary tract infection, dyspnea, and rash. Myelodysplastic syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in 2% of patients with deleterious or suspected deleterious germline BRCA-mutated advanced cancers. The majority of cases were fatal and the duration of therapy with olaparib in patients who developed secondary cancers varied from <6 months to >2 years. Complete blood count should be tested at baseline and monthly following therapy initiation to monitor for MDS/AML. Pneumonitis, including fatal cases, occurred in <1% of patients treated with olaparib. Patients should be monitored for new or worsening respiratory symptoms such as dyspnea, fever, cough, or wheezing. Olaparib was found to be teratogenic and causes embryo-fetal toxicity in rats. It should therefore be avoided during pregnancy and its use should be a combined with an effective contraception during treatment.
Active Ingredient/Synonyms
4-(3-{[4-(cyclopropylcarbonyl)piperazin-1-yl]carbonyl}-4-fluorobenzyl)phthalazin-1(2H)-one | Olaparib |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.