Julphar Bangladesh Ltd.
Juparib 100 Tablet: Each flim coated tablet contains Olaparib INN 100 mg.
Juparib 150 Tablet: Each flim coated tablet contains Olaparib INN 150 mg.
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.
Juparib is indicated as monotherapy for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have previously been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have progressed on or be considered inappropriate for endocrine therapy. Germline BRCA mutation must be confirmed before Juparib treatment is initiated.
Juparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed (PSR) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) to platinumbased chemotherapy.
Dosage and Administration:
There is a risk of medication errors between Olaparib tablets and Olaparib capsules. In order to minimize this risk, check the bottle labels to ensure that the drug being prepared and dispensed is Olaparib tablets and not Olaparib capsules. Prescribers should specify the formulation and dosage of Olaparib on each prescription.
The recommended total daily dose of Juparib tablets is 600 mg, taken as two 150 mg tablets twice daily. The 100 mg tablet is available for dose reduction.
For treatment of ovarian cancer
Patients should start treatment with Juparib no later than 8 weeks after completion of their final dose of the platinum-containing regimen. Patients should have recovered from prior hematologic toxicities prior to starting Juparib therapy (hemoglobin, platelet, and neutrophil levels should be ≤ CTCAE grade 1).
It is recommended that Juparib treatment be continued until progression of the underlying disease or unacceptable toxicity.
Juparib should not be given in combination with other anti-cancer therapy.
Grapefruit or other similar fruit juices that are known to inhibit CYP3A should not be consumed while taking Juparib.
The safety and efficacy of Olaparib has not been established in pediatric patients.
Dose Adjustments for Adverse Reactions:
Treatment may be interrupted to manage adverse events and dose reduction can be considered. The recommended reduced total daily dose of Juparib (olaparib tablet) is 500 mg. If a further dose reduction is required, the recommended reduced total daily dose of Juparib (olaparib tablet) is 400 mg.
Dose Adjustment for Co-administration with CYP3A Inhibitors Concomitant use of strong or moderate CYP3A inhibitors is not recommended and alternative agents should be considered. If a strong CYP3A inhibitor must be co-administered, the recommended reduced total daily dose of Juparib (olaparib tablet) is 200 mg. If a moderate CYP3A inhibitor must be co-administered, the recommended reduced total daily dose of Juparib (olaparib tablet) is 300 mg.
Dose Adjustment for Patients with Renal Insufficiency
For patients with moderate renal impairment (creatinine clearance 31 –
50 ml/min) the recommended reduced total daily dose of Juparib (olaparib tablet) is 400 mg. Juparib is not recommended for patients with severe renal impairment or end-stage renal disease (creatinine clearance
≤30 ml/min), as safety and efficacy have not been studied in these patients. Juparib can be administered to patients with mild renal impairment (creatinine clearance 51 – 80 ml/min) with no dose adjustment.
Juparib (olaparib) is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation.
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 Juparib due to adverse events was 4.9% in the Juparib arm compared with 7.7% in the chemotherapy arm. Anemia and platelet count decrease were the only adverse reactions leading to discontinuation of Juparib in more than one patient.
Interactions with other medicinal products
Co-administration of Juparib (olaparib) with strong or moderate CYP3A inhibitors is not recommended. If a strong or moderate CYP3A inhibitor must be co-administered, the dose of Juparib should be reduced. Co-administration of Juparib with strong or moderate CYP3A inducers is not recommended. In the event that a patient already receiving Juparib requires treatment with a strong or moderate CYP3A inducer, the prescriber should be aware that the efficacy of Juparib may be substantially reduced.
Hematological toxicity has been reported in patients treated with Juparib, including clinical diagnoses and/or laboratory findings of generally mild or moderate (Common Terminology Criteria for Adverse Events [CTCAE] grade 1 or 2) anemia, neutropenia, thrombocytopenia and lymphopenia. Patients should not start treatment with Juparib until they have recovered from hematological toxicity caused by previous anti-cancer therapy (hemoglobin, platelet, and neutrophil levels should be ≤CTCAE grade 1). Baseline testing, followed by monthly monitoring of complete blood counts, is recommended for the first 12 months of treatment and periodically after this time to monitor for clinically significant changes in any parameter during treatment.
Pneumonitis, including fatal cases, occurred in <1% of patients treated with Olaparib. If patients present with new or worsening respiratory symptoms such as dyspnea, fever, cough, wheezing, or a radiological abnormality occurs, interrupt treatment with Olaparib and initiate prompt investigation. If pneumonitis is confirmed, discontinue Olaparib. Embryo-Fetal Toxicity Olaparib can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. Olaparib was teratogenic and caused embryo-fetal toxicity in rats at exposures below those in patients receiving the recommended human dose of 400 mg twice daily. If the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to avoid becoming pregnant while taking Olaparib. If contraceptive methods are being considered, use effective contraception during treatment and for at least one month after receiving the last dose of Olaparib. Drug interaction: Clinical studies of Juparib (olaparib) in combination with other anti-cancer agents, including DNA damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity. The recommended Juparib (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. Use in Pregnancy and Lactation: Pregnancy Olaparib can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. Olaparib was teratogenic 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. Overdosage: 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. Pharmaceutical Information: Storage Condition Store in a dry place below 30° C, protect from light. Keep out of the reach of children. How Supplied Juparib 100 Tablet: Each box contains 120 tablets and one packet silica gel in a sealed plastic container. Juparib 150 Tablet: Each box contains 60 tablets and one packet silica gel in a sealed plastic container. Juparib 150 Tablet: Each box contains 120 tablets and one packet silica gel in a sealed plastic container. Manufactured by: Julphar Bangladesh Ltd.