Lynparza 150mg Astrazeneca supports the treatment of ovarian cancer, breast cancer (7 blisters x 8 tablets)
Dosage form Box of 7 blisters x 8 tablets
Specifications Olaparib
Ingredient
| Composition information | Content |
| Olaparib | 150mg |
Uses
Indications
Lynparza indicated treatment in the following cases:
Ovarian cancer
lynparza is appointed to:
Maintain treatment for adult patients with high -tissue ovarian carcinoma, shellfish or peritoneal cancer in the far stage (Figo stage III and IV), and there is a mutation for BRCA1/2 gene mutations (Germine [Germline] and/or suffering forms [Somatic]), which are responding (completely or partly) after the platinum.
Maintain treatment for adult patients with high -tissue ovarian carcinoma, fallopian tube or peritoneal cancer and recurrent recurrence with platinum (platinum sensitive), these patients are responding (completely or partially) with chemotherapy containing platinum.
Breast cancer
LynParza is indicated for the treatment for treatment in adult patients with the BRCA1/2 genetic mutations (Germline), with phase breast cancer in the remote or metastatic, negative with Her2 receptor. Patients should be previously treated with anthracycline and taxane in the context of complementary or metastatic treatment (new) unless patients are not suitable for these treatments.
Patients with a positive hormonal receptor should be the object of progression during or after the previous hormonal treatment, or patients considered not suitable for endocrine treatment.
Pharmacology
Group Therapy Therapy: Anti -cancer agents, other anti -cancer drugs
Code ATC: L01xx46
olaparib is a strong inhibitor for poly enzymes (ADP ribose) polymerase on humans (PARP-1, PARP-2 and PARP-3), and has been proven about the ability to inhibit the growth of selective tumor cell lines in vitro and tumor growth in Invo when treating single or combined with chemotherapy.
Poly enzyme (ADP ribose) Polymerase (PARP) is necessary during the process of effectively repairing the single DNA fiber fault breakers. An important aspect of Parp (PARP Indair Repair) repair is that after the chromosomal modification, Parp automatically adjusts and separates from DNA to facilitate the approach of base excision enzymes. When Olaparib is associated with the operating position of PARP attached to DNA, it will prevent the dissociation of PARP and hold it on DNA, thus inhibiting the repair process.
During cell copying, this also leads to the formation of DNA (DNABLE Strand Breaks (DSB) DNA (DSB) when the copy branches are copied with a combination of Parp -DNA. On normal cells, the Homologous Recombination Repair-HRR Pathway) is effective in repairing these DNA dual faults. On cancer cells lack the functional components of the recombinant repair process like BRCA1 or 2, the DNA dual fractures cannot be correct or effective repair.
Instead, the replacement processes and easy to be activated, such as the classic process that adds non -similar segments (nho nhoj), leading to the instability of the genome. After some copy rounds, the instability of the genome may reach the level of support and lead to the result of cancer cell death, because cancer cells already have a relatively higher level of DNA damage than normal cells.
In the absence of a BRCA1 or BRCA2 gene mutation, the similar recombinant repair process may be damaged by other mechanisms, although the abnormalities of cause and effect and the penetration have not been completely clarified. The absence of recombinant repair process is one of the main factors that determine the sensitivity of platinum chemotherapy in ovarian cancer and other cancer diseases.
In BRCA1/2 In Vivo, Olaparib deficiency models used after chemotherapy with platinum leading to a delay in tumor progression and increased survival time compared to only chemotherapy with platinum, this is correlated with maintenance time with olaparib.
Detect the BRCA1/2 gene mutation
Local/ 2 BRCA1/ 2 gene mutation tests on blood samples and/ or tumor samples have been used in different studies. Depending on the use and consensus for international classification, the BRCA1/ 2 gene mutations are classified as dangerous/ suspected of danger or pathogenic/ likely to cause disease. Genetic tests should be conducted by an experienced laboratory and used the recognized testing method.
Pharmacokinetics
absorption
After taking Olaparib tablets (2 x 150mg), the drug is quickly absorbed with the average peak concentration in plasma usually reaches 1.5 hours after taking the drug.
Simultaneously use with food slowed (2.5 hours slow and c max decreased by about 21%) but did not significantly affect the absorption level of Olaparib (AUC increased by 8%). Therefore, Lynparza can be used or not accompanied by food.
Distribution
The cohesion with plasma protein in vitro is about 82% at a concentration of 10µg/ml, approximately cmax.
In vitro, the level of plasma protein binding of Olaparib depends on the dose; The limit rate is about 91% at a concentration of 1µg/ml, reduced to 82% at a concentration of 10µg/ml and up to 70% at 40µg/ml. In pure protein solution, the ratio of olaparib associated with albumin is about 56% and does not depend on Olaparib concentration. When using the same test, the ratio attached to Alpha-1 Glycoprotein is 29% at a concentration of 10µg/ml with the trend of reducing cohesion at higher concentrations.
Metabolism
In vitro research shows that CYP3A4/5 is the enzyme responsible for the metabolism of olaparib.
After taking 14C-olaparib for female patients, Olaparib unchanged accounts for the majority of radioactive in plasma (70%) and is the main component found in both urine and feces (15% and 6% of the dose levels respectively). Olaparib metabolizes strongly. Most metabolic processes are caused by oxidation reactions with some components created through the glucuronide or sulfate conjugate process. Up to 20, 37 and 20 metabolites were detected in turns in plasma, urine and feces, mostly only
In vitro research shows that Olaparib is less inhibited or does not inhibit UGT2B7 or CYPS 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6 or 2E1 and is not considered as a clinical time inhibitor of any CYP enzyme. Olaparib inhibits UGT1A1 In Vitro, however, PBPK simulation shows that this is not clinically important. In vitro, olaparib is the substrate of P-GP transportation, however, it is not necessarily clinical significance.
In vitro, data also shows that olaparib is not the substrate for OATP1B1, OATP1B3, OCT1, BCRP or MRP2 and not OatP1B3, OAT1 or MRP2 inhibitors.
Elimination
After a single dose of 14C-olaparib, ~ 86% of the radioactive amount has been recovered during a 7-day collection, ~ 44% in urine and ~ 42% in feces. Mostly excreted in the form of metabolites.
Special patient groups
In PK analysis based on population, patient age, gender, weight or race (including white and Japanese patients) are not significant covariates.
Patients with renal failure
In patients with mild renal failure (Creatinin clearance 51 - 80ml/minute), AUC increased 24% and CMAX increased by 15% compared to patients with normal kidney function. No need to adjust the lynparza dose for patients with mild renal failure.
In medium renal impaired patients (Creatinine clearance 31 - 50ml/minute), AUC increased by 44% and CMAX increased by 26% compared to patients with normal kidney function. Lynparza dose adjustment is recommended for patients with medium renal failure.
There is no data in patients with severe renal impairment or end -stage renal disease (creatinine clearance
Patients with liver failure
In patients with mild liver failure (classification of Pugh A), AUC increased by 15% and CMAX increased by 13% and in medium liver impairment patients (classification of Pugh B), AUC increased by 8% and CMAX decreased by 13% compared to patients with normal liver function. No need to adjust the lynparza dose for patients with mild or medium liver failure. No data in patients with severe liver failure (classification of Pugh C).
Children
No research on pharmacokinetics of Olaparib in children.
Before taking Lynparza 150mg Astrazeneca supports the treatment of ovarian cancer, breast cancer (7 blisters x 8 tablets)
How to use
lynparza oral use.
Lynparza tablets should be swallowed and not chewed, crushed, dissolved or divided. Can take lynparza attached or not accompanied by food.
Dosage
Lynparza treatment should be started and monitored by the doctor who has experience using anti -cancer drugs.
Detecting the mutations of the BRCA1/2 gene mutation
Before starting to use Lynparza for treatment to maintain step 1 on high-grade epithelial ovarian ovarian cancer (EOC), EOC), Fallopian tube cancer-FTC) or Primary Peritoneal Cancer (PPC), patients must be confirmed about dangerous situation (Deleterious) or suspected danger (Suspected Deleterious) in the form of genetic (germline) and/or incorrect form (somatic) of the BRCA 1 or 2 gene in a quality test.
Do not require BRCA1/2 test before taking Lynparza for maintenance treatment when being relapsed by EOC, FTC or PPC, and is fully responding or partly with platinum -containing therapy.
For metastatic breast cancer with gene mutations BRCA1/2 genetic forms (germline) and negative with receptor of epidermal growth factor 2 (Her2), patients must be confirmed about the mutation of the BRCA1/2 genetic gene (Germline) dangerous or suspected danger before starting Lynparza. Genetic mutations BRCA1/2 genetic forms (Germline) must be determined by the experienced laboratory using recognized testing methods. Currently, there is no data to prove clinical value of BRCA1/2 tests in breast cancer tumors.
Genetic advice for patients with a BRCA1/2 gene mutation test should be implemented in accordance with the regulations of the host country.
Dosage
The recommended dose is 300mg (two tablets 150mg) x 2 times/day, equivalent to a total daily dose of 600 mg.
Patients with high tissue ovarian carcinoma, fallopian tube or peritoneal cancer recurrent with platinum (PSR), patients who are responding (completely or partial) with chemotherapy containing platinum should be started with Lynparza less than 8 weeks after completing the final dose of platinum treatment regimen.
Treatment time
Maintain step 1 on ovarian cancer in the far stage has a BRCA gene mutation:
Special patient groups
Elderly:
Patients with renal failure:
Children: The safety and effectiveness of Lynparza in children and adolescents have not been established. No data available.
Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.What do
do when using overdose? Do not record unwanted adultery reactions in a few patients taking olaparib daily doses up to 900mg in two days. There are no overdose symptoms and no specific treatment in the case of lynparza overdose. In case of overdose, doctors should follow general support measures and should treat patients according to symptoms. What to do when forgetting a dose?
Side Effects
When using Lynparza often has unwanted effects (ADR) such as:
Very common, ADR> 1/10
Common, 1/10 Uncommon, 1/1000 Instructions on how to handle ADR When experiencing side effects of the drug, it is necessary to stop using and notify the doctor or go to the nearest medical facility for timely treatment.
Warnings
Before using the drug you need to read the instructions carefully and refer to the information below.
Contraindicated
Lynparza drug is contraindicated in the following cases:
Women who are breastfeeding during treatment and 1 month after the last dose.
Be cautious when using
Hematology toxicity
Hematology has been recorded in patients treated with Lynparza, including anemia, neutropenalia, thrombocytopenia and mild or medium lymphocytic lymphocytes (level 1 or 2 according to the criteria for evaluating adverse events - CTCAE), detected on clinical and/or subclinical diagnosis. Patients should not start treatment with Lynparza until the hematology recovery due to previous anti -cancer therapy (hemoglobin concentration, platelet and neutrophils should ≤ ctcae level 1). Checking the general blood count before treatment and monitoring monthly is recommended in the first 12 months of treatment and periodically after this time to monitor significant clinical changes of any parameter during treatment.
If a patient has a serious hematology or dependent on blood transfusion, it is necessary to temporarily suspend the treatment with Lynparza and start appropriate hematological testing. If the blood parameters are still clinically abnormal after 4 weeks of stopping the lynparza dose, the analysis of bone marrow analysis and/ or blood cytetical analysis.
Acute medullary dysplauma syndrome
The new rate of entire medullary dysplasma syndrome/ acute myeloid leukemia (myelodysplified syndrome [MDS]/ acute myeloid leukaemia [AML]) in patients treated in clinical trials with single -therapy lynParza therapy, including monitoring the ability to live in the long term, is Olaparib treatment time in patients with MDS/AML varies from 2 years; Data with longer medication time is still limited. All patients with potential risk factors for MDS/AML development, have been chemotherapy earlier with platinum containing agents.
Many patients have also been treated with other DNA destruction agents and radiation. The majority of reports are the BRCA 1 or 2 genetic mutations (Germline) (GBRCA1/2). The new ratio of MDS/AML is similar between patients with Genetic BRCA1 gene mutations (Germline) and patients with genetic mutations BRCA2 (Germline) (1.7% respectively compared to 1.4%).
Some patients have a history of cancer before or bone marrow dysplasia. If MDS and/ or AML are confirmed during treatment with Lynparza, it is recommended to stop using Lynparza and the patient should be properly treated.
Pneumoni (pneumonitis)
Pneuminitis (pneumonitis), including deaths, has been recorded If the patient has new or more severe respiratory symptoms such as shortness of breath, cough and fever, or observing an abnormal chest image, lynparza treatment should be temporary and start checking immediately. If the pneumonia is not due to an infection (pneumonitis), it is recommended to stop treating Lynparza and patients with appropriate treatment.
embryo poisoning
Based on the mechanism of operation of the drug (Parp inhibitor), Lynparza can be harmful to the fetus when used for pregnant women. Preventive studies on mice have shown that Olaparib has a side effect on the survival of the embryo and causes severe fetal defects when taking the drug below the recommended dose on the expected 300 mg, twice/day.
Pregnant women/are taking birth control pills
LynParza should not be used during pregnancy. Women who have the ability to give birth must use two reliable contraception before starting lynparza treatment, while treating and taking one month after taking the last lynparza dose. It is advisable to recommend using two highly effective and mutual contraceptives. Men and female spouses are likely to have a baby should use reliable contraception during treatment and use for 3 months after receiving the last lynparza dose.
Drug interaction
Do not simultaneously use Lynparza with strong or medium CYP3A inhibitors. If you have to be used simultaneously with strong or medium CYP3A inhibitors, lynparza dose should be reduced.
Do not simultaneously use Lynparza with strong or medium CYP3A induction substances. In the case of patients who have lynparza, need to be treated with strong or medium CYP3A induction drugs, the prescription should note that the effectiveness of Lynparza may be significantly reduced.
contraceptive in men
It is unclear whether Olaparib or its metabolites are found in semen. During treatment and for 3 months after taking the last lynparza dose, male patients must use condoms when having sex with pregnant women or with women who have the ability to give birth. The female patient's spouse must also use highly effective contraception if they are likely to have a baby. Male patients must not donate sperm during treatment and for 3 months after taking the last lynparza dose.
The ability to drive and operate machinery
Lynparza has a moderate effect on the ability to drive and operate machinery. Patients who are taking Lynparza may be tired, weak or dizzy. If these symptoms encounter, patients should be cautious when driving or operating machinery.
Pregnancy
Women who have the ability to have children should not become pregnant during lynparza treatment and not pregnant at the beginning of treatment. Pregnancy tests must be performed in all women who are likely to have children before treatment and periodic consideration during treatment.
Women who have the ability to give birth must use two reliable contraceptive measures before starting lynparza treatment, while treatment and continuing to take 1 month after taking the last lynparza dose, unless the option of abstinence methods for contraception. Recommendations to use two effective and mutual contraception.
Because olaparib can not be ruled out, it can reduce the contact concentration of the substrate of CYP2C9 through enzyme induction, the effectiveness of endocrine contraceptives may be reduced if used with olaparib. Therefore, an additional method of contraception is not hormonal during treatment. For women with cancer dependent on hormones, two measures should be considered without hormonal contraception.
Animal studies have shown reproductive toxicity including serious teratogenic effects and affect the survival of the embryo in mice at the level of body contact with the mother's medication in the mother rat lower than in humans at the dose of treatment. There is no data on the use of olaparib in pregnant women, however, according to the mechanism of action of Olaparib, Lynparza should not be used in pregnant women and women who have the ability to give birth without using reliable contraception during treatment and 1 month after taking the last lynparza dose.
The period of breastfeeding
There is no animal research on the secretion of olaparib in breast milk. It is unknown whether Olaparib or its metabolites are excreted through breast milk. Lynparza is contraindicated for breastfeeding women and for 1 month after the last dose, due to the pharmacological properties of the product.
Interactive drug
Interactive pharmaceutical force
Clinical studies on Olaparib combined with other anti -cancer drugs, including DNA harmful agents, shows the potential and prolonged toxic inhibition of marrow. The recommended dose of Lynparza Unrequited treatment is not suitable for combining with the anti -cancer inhibiting medications.
Combining olaparib with vaccines or immunosuppressive drugs has not been studied. Therefore, it is necessary to be cautious if they share these drugs with Lynparza and patients should be closely monitored.
Pharmacokinetic interaction
The effect of other drugs on olaparib
CYP3A4/5 are the isozyme mainly responsible for the metabolism of olaparib.
A clinical study to assess the impact of Itraconazole, a known CYP3A inhibitor, showed that it was simultaneously used with Olaparib, increasing Olaparib's CMAX median to 42% (90% CI: 33 - 52%) and AUC median increased by 170% (90% CI: 144 - 197%). Therefore, it is not recommended to use lynparza with strong CYP3A inhibitors (for example, iTraconazole, telithromycin, clarithromycin, strong protease inhibitors with ritonavir or cobicistat, boceprevir, telaprevir) or medium CYP3A inhibitors (for example Erenthromycin, diltiacin, diltia, fluconazole, verapamil).
If used with strong or medium CYP3A inhibitors, lynparza dose should be reduced. The reduction of the lynparza dose is recommended to be 100 mg, twice daily (equivalent to a total daily dose of 200 mg) when used with strong CYP3A inhibitors or 150 mg, twice daily (equivalent to a daily daily dose of 300 mg) when used with medium CYP3A inhibitors. Also do not use grapefruit juice (Grapefruit) while treating Lynparza because grapefruit juice is also CYP3A inhibitor.
A clinical study to evaluate the impact of rifampicin, a known CYP3A touch substance, shows that the simultaneous use with Olaparib reduces the CMAX median of Olaparib 71% (90% CI: 76 - 67%) and AUC median decreased by 87% (90% CI: 89 - 84%). Therefore, the known strongly induction substances of this isozyme (for example, Phenytoin, Rifampicin, Rifapentine, Carbamazepine, Nevirapine, Phenobarbital and St John’s Wort) are not recommended to be used with Lynparza, because it can significantly reduce the efficiency of LynParza. The intensity of the impact of medium to strong induction drugs (for example: Efavirenz, Rifabutin) for the exposure of olaparib has not been established, so it should not be used simultaneously Lynparza with these drugs.
The effect of olaparib on other drugs
Olaparib inhibits CYP3A4 In Vitro and is predicted as a light CYP3A inhibitor in Vivo. Therefore, it is necessary to be careful when combining the substrates that are sensitive to CYP3A or the substrate with narrow treatment windows (eg Simvastatin, Cisapride, Cyclosporine, Alkaloid Mushroom, Fentanyl, Pimozide, Sirolimus, Tacrolimus and Quetiapine) with Olaparib. Clinical monitoring recommendations for patients who are concurrently using CYP3A substrate with narrow treatment windows with Olaparib.
The touch of CYP1A2, 2B6 and 3A4 has been shown in vitro by CYP2B6, which is most likely to be induced at a clinical level. It is also impossible to rule out the possibility of Olaparib touch CYP2C9, CYP2C19 and P-GP. Therefore, Olaparib when shared can reduce exposure to the substrates of these transporter metabolic enzymes and proteins. The effectiveness of some hormonal contraceptives can be reduced if used with olaparib.
In vitro, Olaparib inhibit the P-GP transport protein (IC50 = 76µm), so it is not possible to rule out Olaparib that can cause clinical-related drug interactions with the background of P-GP (such as simvastatin, pravastatin, dabigatran, digoxin and colchicine). Clinical monitoring is required for patients to use simultaneously with this drug.
In vitro, Olaparib has been shown to be inhibitors of BCRP, OATP1B1, Oct1, OCT2, OAT3, Mate1 and Mate2K. Olaparib cannot be excluded that the exposure of BCRP (for example, Methotrexate, Rosuvastatin), OATP1B1 (e.g. Bosentan, Glibenclamide, Repaglinide, Statin and Valsartan), OCT1 (for example, Metformin), OCT2 (for example, CREATILININ), OAT3 (for example Furosemide and Furosemide. Methotrexate), Mate1 (for example Metformin) and Mate2K (for example Metformin). In particular, be careful if using olaparib in combination with any statin.
Combined with Anastrozole, Letrozole and Tamoxifen
A clinical study was conducted to evaluate the combination of Olaparib with Anastrozole, Letrozole or Tamoxifen. It has not yet been significantly interacted with Anastrozole or Letrozole while Tamoxifen reduces the level of contact with Olaparib 27%. The clinical involvement of this impact has not been known. Olaparib does not affect the pharmacokinetics of Tamoxifen.
Storage
Store at a temperature not exceeding 30 ° C.
Store in the original packaging to avoid moisture.
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