Index of drugs

As monotherapy, in the maintenance treatment of adult patients with platinum-susceptible serous ovarian cancer with low degree of differentiation, oviduct cancer or primary peritoneal carcinoma, with BRCA (hereditary and / or somatic) mutation, who received a response (complete response or partial response) to chemotherapy based on platinum compounds.

One capsule contains 50 mg of olaparib.

An anti-cancer drug. A strong inhibitor of human enzymes referred to as poly-ADP-ribose polymerases (PARP-1, PARP-2 and PARP-3). It inhibits the growth of some cancer cell lines under conditionsin vitro and the growth of tumorsin vivo, used as the sole drug (alone) or in combination with recognized chemotherapeutics. After oral administration, it is absorbed quickly. C_max in plasma is usually achieved 1-3 hours after taking the dose. When repeated doses are administered, there is no significant accumulation of the drug, and steady state exposure is achieved after about 3-4 days. Administration of the drug at the same time as food slows down the rate of absorption (T._max delayed by 2 h), and slightly increases the absorption rate (AUC increases by approx. 20%). Olaparib binding to proteins under conditionsin vitro at plasma concentrations achieved after administration of 400 mg twice daily is approximately 82%. Olaparib is metabolized to a significant extent. CYP3A4 is the major enzyme responsible for the metabolism of olaparib. Most of the metabolism is based on oxidation reactions leading to a series of substances that are then coupled to glucuronate or sulfate. After a single dose, approximately 44% are excreted in the urine and 42% in the faeces, mainly in the form of metabolites. T_0,5 in the elimination phase is 11.9 hours.

Hypersensitivity to the active substance or to any of the excipients. Breastfeeding during treatment and 1 month after the last dose.

Patients should not initiate olaparib treatment until resolution of haematological toxicity due to anti-cancer therapy used earlier (hemoglobin, platelet counts and neutrophils should be within normal range or CTCAE level 1). It is recommended that a complete blood count should be performed initially and then repeated at monthly intervals for the first 12 months of treatment and periodically thereafter in order to monitor the occurrence of clinically significant changes in haematological parameters during treatment. In case of severe haematological toxicity, the patient should be discontinued and appropriate hematological tests performed. If abnormal hematology parameters persist for 4 weeks after discontinuing olaparib, bone marrow and / or cytogenetic analysis is recommended. In a small number of patients receiving olaparib alone or in combination therapy with other anticancer drugs, the occurrence of myelodysplastic syndrome / acute myeloid leukemia (MDS / AML) has been reported; in most cases fatal. The duration of olaparib treatment in patients with secondary MDS / AML varied between <6 months and> 2 years. All patients had potentially favorable factors for the occurrence of MDS / AML; most of these cases occurred in carriers of hereditary gBRCA mutations, and in some patients the occurrence of malignant tumors or a history of bone marrow dysplasia. All patients received prior chemotherapy regimens containing platinum compounds, many of them also received other DNA damaging substances and underwent radiotherapy. If MDS and / or AML are confirmed during treatment with olaparib, it is recommended that the patient undergo appropriate treatment. If the patient is advised to use additional anticancer treatment, olaparib should be discontinued and should not be used in combination with other anticancer medicines. The occurrence of pneumonia was reported in a small number of patients taking olaparib; in some cases fatal.Cases of pneumonia did not have consistent clinical characteristics and were influenced by a number of predisposing factors (cancer and / or tumor metastases in the lungs, pre-existing primary lung disease, history of smoking, and / or prior chemotherapy and radiotherapy). If the patient develops new or worsening respiratory symptoms such as dyspnea, cough and fever, or if abnormalities occur in radiological studies, olaparib should be discontinued and diagnostic tests should be carried out immediately. If the diagnosis of pneumonia is confirmed, olaparib should be discontinued and appropriate therapy initiated immediately.

Olaparib should not be used during pregnancy and in women of childbearing potential who do not use reliable contraceptive methods throughout treatment and for 1 month after the last dose. Women of childbearing potential should not become pregnant while taking olaparib and may not be pregnant when starting treatment. Before starting treatment, all premenopausal women should undergo pregnancy tests. Women of childbearing potential must use effective contraceptive measures throughout treatment and for 1 month after the last dose of olaparib. Due to the possible interaction of olaparib with hormonal contraceptives, it is recommended to consider additional non-hormonal methods of contraception and regular pregnancy tests during treatment. The drug is contraindicated during breastfeeding and for 1 month after the last dose.

The use of olaparib as monotherapy was associated with adverse reactions of generally mild or moderate severity (CTCAE level 1 or 2) and usually not requiring discontinuation of the drug.The incidence of adverse reactions of all severity levels according to CTCAE. Very common: decreased appetite, headache, dizziness, disturbed taste, nausea, vomiting, diarrhea, indigestion, tiredness (including weakness), anemia, neutropenia, lymphopenia, increased blood creatinine, increased mean volume of red blood cells. Common: epigastric pain, stomatitis, thrombocytopenia.The incidence of an adverse reaction with grade 3 or greater according to CTCAE. Very common: anemia, lymphopenia. Common: nausea, vomiting, diarrhea, fatigue (including weakness), neutropenia, thrombocytopenia. Uncommon: decreased appetite, dizziness, headache, epigastric pain, stomatitis, increased blood creatinine. Common gastrointestinal side effects (grade 1 or 2 according to CTCAE) have been commonly reported with olaparib, they are transient and can be remedied by discontinuation, dose reduction and / or other medicines (eg antiemetics). ). Preventive use of antiemetic drugs is not necessary.

Orally. Treatment should be started and supervised by a doctor experienced in the use of anticancer medicines. Before starting treatment, it is necessary to confirm the presence of mutations in the breast cancer susceptibility gene (BRCA) in the patient (in germline cells or in tumor cells). The status due to the BRCA mutation should be determined by an experienced laboratory using a validated test. Limited data are available for patients with somatic BRCA mutations in the tumor. Genetic counseling should be performed for patients with BRCA mutations, according to local regulations. Adults: the recommended dose is 400 mg (8 capsules) 2 times daily, which corresponds to a total daily dose of 800 mg. Patients should start treatment with olaparib no later than 8 weeks after the last dose of the drug in the scheme containing platinum derivatives. It is recommended that treatment be continued until progression of the underlying disease. There is no data on repeat olaparib treatment after progression. If you miss a dose, take the Next dose at the scheduled time. The use of the drug can be discontinued to manage side effects such as nausea, vomiting, diarrhea and anemia; a dose reduction may also be considered. The recommended reduced dose is 200 mg 2 times a day.If further dose reduction is necessary, it may be considered to be reduced to 100 mg twice daily.Special groups of patients. Elderly patients do not need to adjust the starting dose of the drug. Limited clinical data are available for use in patients aged 75 years and above. It can be given to patients with mild renal insufficiency (creatinine clearance> 50 ml / min). It can be used in patients with moderate renal impairment (creatinine clearance <50 ml / min) or severe renal impairment (creatinine clearance <30 ml / min) only if the benefits outweigh the potential risk, and the patient must be carefully monitored for renal function and the occurrence of side effects. The drug is not recommended for use in patients with hepatic impairment (serum bilirubin serum greater than 1.5 times ULN), because the safety and efficacy of the drug in this group have not been determined. There are only limited clinical data on the use of the drug in non-Caucasian patients. However, no dose adjustment is required due to ethnicity. Very limited clinical data are available for patients with 2-4 fitness status. The safety and efficacy of the drug in children and adolescents have not been determined.Method of administration. The preparation should be taken at least 1 hour after a meal and refrain from eating for at least 2 hours after taking the medicine.