Paclitaxel concentrate for the p-ra 300mg/50ml №1

Indications and usage

- ovarian cancer (first-line therapy in combination with platinum preparations and second-line therapy for metastases after standard therapy, which did not give a positive result);

- breast cancer (as a first and second line therapy, as well as an adjuvant treatment);

- non-small cell lung cancer (first-line therapy for patients who are not planning surgical treatment and / or radiation therapy / in combination with Cisplatin /);

- Kaposi's sarcoma in AIDS patients (second-line therapy, after ineffective therapy with liposomal anthracyclines).

Enter in / in.

Paclitaxel can be used both as a monotherapy and in combination with other anticancer drugs. The dose and regimen of the drug is selected individually.

To prevent severe hypersensitivity reactions, all patients should be premedicated using corticosteroids, histamine N blockers.₁- and H₂-receptors. The recommended premedication scheme is 20 mg of Dexamethasone (or its equivalent) orally for approximately 12 hours and 6 hours before the administration of paclitaxel-Ebeve, 50 mg of diphenhydramine (or its equivalent) in / and 300 mg of cimetidine or 50 mg of Ranitidine / in 30-60 minutes before the introduction of the drug Paclitaxel-Ebeve.

First-line ovarian cancer Chemotherapy

A combination regimen of paclitaxel and cisplatin is recommended. Paclitaxel is administered at a dose of 175 mg / m² body surfaces within 3 hours of intravenous infusion or at a dose of 135 mg / m² during the 24-hour intravenous infusion, then cisplatin is administered at a dose of 75 mg / m². Intervals between courses - 3 weeks.

Chemotherapy second-line ovarian cancer

Paclitaxel is recommended to be administered at a dose of 175 mg / m² body surface by 3-hour intravenous infusion. Intervals between courses - 3 weeks.

Adjuvant Chemotherapy for Breast Cancer

Paclitaxel is prescribed after chemotherapy with anthracyclines and cyclophosphamide. Paclitaxel is recommended to be administered at a dose of 175 mg / m² IV for 3 hours. 4 courses with intervals between courses - 3 weeks.

First line cancer chemotherapy for breast cancer

In the case of combined use with doxorubicin (at a dose of 50 mg / m² body surface), paclitaxel must be administered 24 hours after doxorubicin.

The recommended dose of paclitaxel is 220 mg / m² the surface of the body when administered by 3-hour intravenous infusion. Intervals between courses - 3 weeks.

When combined use with trastuzumab, Paclitaxel is recommended to be administered at a dose of 175 mg / m² body surface by 3-hour intravenous infusion with an interval between courses of 3 weeks. Paclitaxel can be administered the next day after the first dose of trastuzumab or immediately after the subsequent doses, if the previous dose of trastuzumab was well tolerated.

Chemotherapy second-line breast cancer

Paclitaxel is recommended to be administered at a dose of 175 mg / m² by 3-hour intravenous infusion. Intervals between courses - 3 weeks.

Chemotherapy for advanced non-small cell lung cancer

A combination regimen of paclitaxel and cisplatin is recommended. Paclitaxel is administered at a dose of 175 mg / m² body surface by 3-hour intravenous infusion, then cisplatin is administered at a dose of 80 mg / m². Intervals between courses - 3 weeks.

Chemotherapy for Kaposi's sarcoma with AIDS

Paclitaxel is recommended to be administered at a dose of 100 mg / m² by 3-hour IV infusion. Intervals between courses - 2 weeks.

Subsequent doses Paclitaxel is administered individually, depending on the tolerance of therapy. The next dose of paclitaxel can be administered only after increasing the number of neutrophils to ≥1500 cells / μl (≥1000 cells / μl in the case of Kaposi’s sarcoma), and platelets to levels> 100000 cells / mm3 (> 75000 cells / mm³ in case of Kaposi's sarcoma). Patients who have experienced severe neutropenia (neutrophil count less than 500 cells / mcl for 7 days or more) or severe peripheral neuropathy, reduce the following doses by 20% (25% in the case of Kaposi's sarcoma).

There is currently insufficient data to make recommendations for dose adjustment for patients with impaired liver function mild or moderate severity. Patients with severely impaired liver function paclitaxel should not be administered.

Terms of preparation of the solution for infusion

When preparing, storing and administering Paclitaxel-Ebeve drug, you should use equipment that does not contain PVC: for example, from glass, polypropylene or polyolefin.

A solution of the drug is prepared by diluting the concentrate to a final concentration of paclitaxel from 0.3 to 1.2 mg / ml. As a diluting solution can be used: 0.9% sodium chloride solution, 5% dextrose solution, 5% dextrose solution in 0.9% sodium chloride solution, 5% dextrose solution in Ringer's solution. Prepared solutions may opalesce due to the presence of the base carrier in the formulation. With the introduction of the drug should use a system with a membrane filter (pore size not more than 0.22 microns).

Solutions for infusions prepared by diluting Paclitaxel-Ebeve with a 0.9% solution of sodium chloride or 5% dextrose are physically and chemically stable for 51 hours when stored at 25 ° C and 14 days when stored at 5 ° C. From a microbiological point of view, the solution for infusion should be administered immediately after preparation. If the solution is not used immediately after preparation, the storage time should not exceed 24 hours at a temperature between 2 ° and 8 ° C, unless the solution has been prepared under controlled aseptic conditions.

To reduce the risk of sediment formation, the infusion solution must be injected immediately after dilution and excessive shaking, vibrations and agitation should be avoided.

The infusion system must be thoroughly flushed before use. In the process of introduction, it is necessary to regularly monitor the appearance of the solution and stop the infusion if sediment is detected.

Adverse reactions

The frequency and severity of side effects are dose-dependent.

Determination of the frequency of side effects: very often -> 10%, often - from 1 to 10%, infrequently - from 0.1% to 1%, rarely - from 0.01 to 0.1%, very rarely - less than 0.01%.

Hemic and lymphatic: very often - myelosuppression, neutropenia, thrombocytopenia, anemia, leukopenia, bleeding; rarely febrile neutropenia; very rarely, acute myeloid leukemia, myelodysplastic syndrome.

Nervous system: very often - neurotoxic effects (mainly peripheral neuropathy), paresthesias; rarely, motor neuropathy (moderately pronounced weakness of the distal muscles, difficulty in performing precise movements); very rarely - autonomic neuropathy (leading to paralytic ileus and orthostatic hypotension), major epileptic seizures (grand mal), convulsions, encephalopathy, dizziness, headache, confusion, ataxia.

Cardiovascular: often - bradycardia, lowering blood pressure; infrequently - cardiomyopathy, asymptomatic ventricular tachycardia, AV-blockade, syncope, increased blood pressure, myocardial infarction, vascular thrombosis, thrombophlebitis; very rare - atrial fibrillation, supraventricular tachycardia, shock.

Special senses: very rarely - lesions of the optic nerve and / or visual impairment (atrial scotoma), hearing loss, tinnitus, dizziness.

Respiratory: rarely - shortness of breath, pleural effusion, interstitial pneumonia, pulmonary fibrosis, pulmonary embolism, respiratory failure, radiation pneumonitis in patients simultaneously undergoing radiation therapy; very rare - cough.

From the digestive system: very frequent - nausea, vomiting, diarrhea, inflammation of the mucous membranes; rarely - pancreatitis, intestinal perforation, ischemic colitis; very rarely - anorexia, constipation, mesenteric thrombosis, pseudomembranous colitis, esophagitis, ascites, neutropenic colitis , hepatic necrosis, hepatic encephalopathy (there are single reports of fatal outcome).

From the skin and skin appendages: very often - alopecia; often - transient small changes in nails and skin (pigmentation disorders, discoloration of the nail bed); rarely - itchy skin, rash, erythema; very rarely - Stevens-Johnson syndrome (ulceration of the oral mucosa, throat, eyes, genitals, other skin and mucous membranes), epidermal necrolysis, erythema multiforme, exfoliative dermatitis, urticaria, onycholysis.

From the musculoskeletal system: very often - arthralgia, myalgia.

On the part of the immune system: very frequent infections (mainly of the urinary tract and upper respiratory tract); infrequently, serious hypersensitivity reactions requiring therapeutic measures (namely, a decrease in blood pressure,angioedema, respiratory distress syndrome, generalized urticaria, chills, back pain, chest pain, tachycardia, abdominal pain, pain in the extremities, pronounced sweating, increased blood pressure); rarely - anaphilatoid reactions.

From the laboratory indicators: often - an increase in the activity of hepatic transaminases, an increase in the concentration of alkaline phosphatase, bilirubin, creatinine in serum.

Local reactions: often - pain, localized edema, erythema, induration and skin pigmentation at the injection site; extravasation may cause inflammation and necrosis of the subcutaneous tissue.

Other: rarely - asthenia, fever, dehydration, general weakness.

- hypersensitivity to the drug;

- hypersensitivity to other drugs, the dosage form of which includes polyoxyethylene castor oil;

- the initial content of neutrophils less than 1500 / mcl in patients with solid tumors;

- the initial (or registered in the treatment process) neutrophil count is less than 1000 / μl for Kaposi’s sarcoma in AIDS patients;

- pregnancy;

- lactation (breastfeeding);

- children's age (safety and efficacy not established).

WITH caution used in patients with oppression of bone marrow hematopoiesis (including after chemotherapy or radiation therapy), liver failure, acute infectious diseases (includingherpes zoster, chickenpox, herpes), severe course of coronary artery disease, with a myocardial infarction in history, with arrhythmias.

Controlled studies of the use of paclitaxel in pregnant women have not been conducted. Animal studies have shown embryotoxic, teratogenic and mutagenic effects of paclitaxel. Therefore, during pregnancy, paclitaxel should not be used.

It is not known whether paclitaxel is excreted in breast milk, therefore, in order to avoid the toxic effect of the drug on an infant, breastfeeding should be stopped during the treatment period.

Patients during treatment with Paclitaxel-Ebeve and at least 3 months after the end of therapy should use reliable methods of contraception.

WITH caution prescribed for liver failure.

There is currently insufficient data to make recommendations for dose adjustment for patients with impaired liver function mild or moderate severity. Patients with severely impaired liver function paclitaxel should not be administered.

The safety and efficacy of Paclitaxel-Ebeve in children has not been established.

The use of Paclitaxel-Ebeve should be carried out under the supervision of a physician with experience in working with anticancer chemotherapeutic drugs.

With the development of severe hypersensitivity reactions, administration of the drug Paclitaxel-Ebeve should be immediately stopped and symptomatic therapy should be initiated, and repeated administration of the drug should not be carried out.

If Paclitaxel-Ebeve is used in combination with cisplatin, Paclitaxel-Ebeve must be administered first, followed by cisplatin.

When working with Paclitaxel-Ebeve, care must be taken (as when working with other cytotoxic substances), use gloves and avoid contact with skin or mucous membranes. After contact with skin, wash it thoroughly with soap and water; eye contact with plenty of water.

Control of laboratory parameters

During treatment, it is necessary to regularly monitor the picture of peripheral blood, blood pressure, heart rate and the number of breaths (especially during the first hour of infusion).

ECG monitoring should be carried out before the start of therapy and regularly during treatment.

With the development of AV-conduction disturbances during repeated administrations, continuous ECG monitoring is necessary.

Use in pediatrics

The safety and efficacy of Paclitaxel-Ebeve in children has not been established. Pediatric use is contraindicated.

Influence on ability to drive motor transport and control mechanisms

Because of the likelihood of side effects, such as headache, dizziness, drowsiness, during treatment, patients should refrain from practicing potentially hazardous activities that require increased concentration and psychomotor speed.

Precautions for handling and disposing of unused medication

Caution should be exercised when working with Paclitaxel-Ebeve. Dilute the drug should be in aseptic conditions in a specially designated room. This should be done by trained personnel. It is necessary to take all measures to prevent paclitaxel solution on the skin and mucous membranes, in particular, to use protective clothing (gown, cap, mask, goggles and disposable gloves). Inhalation of vapors or sprayed solutions of paclitaxel reported the occurrence of shortness of breath, chest pain, burning sensation in the throat, nausea.

If paclitaxel is in contact with the skin or mucous membranes, rinse thoroughly with soap and water or (eyes) with plenty of water.

The drug should not be frozen, since it may form a precipitate. Such a precipitate usually dissolves when the vial is heated to room temperature (25 ° C). If the solution in a previously frozen vial remains cloudy or there is an insoluble precipitate in it, the drug cannot be used and such a vial should be destroyed. The prepared solution for infusion does not need to be protected from light.

The remnants of the drug and all the tools and materials that were used to prepare the solution for infusion and the introduction of Paclitaxel-Ebeve should be disposed of in accordance with the standard hospital procedure for disposal of waste of cytotoxic substances, taking into account existing regulations for the destruction of hazardous waste.

Symptoms: oppression of bone marrow function, peripheral neuropathy, inflammation and ulceration of the mucous membranes.

Treatment: symptomatic. Antidote to paclitaxel is not known.

Cisplatin reduces the total clearance of paclitaxel by 20%, therefore, in combination chemotherapy, paclitaxel must be administered before cisplatin. More pronounced myelosuppression is observed when paclitaxel is administered after cisplatin. With combination chemotherapy (paclitaxel and cisplatin), the risk of developing renal failure is higher than with cisplatin monotherapy.

The simultaneous appointment with cimetidine, ranitidine, dexamethasone or diphenhydramine does not affect the connection of paclitaxel with plasma proteins .

Since the elimination of doxorubicin and its active metabolites may decrease with a decrease in the time interval between the administration of paclitaxel and doxorubicin, paclitaxel must be administered 24 hours after doxorubicin.

Information on the potential interaction of paclitaxel with inhibitors and inductors of cytochrome P450 system isoenzymes (in particular CYP3A4 isoenzyme) is limited, therefore caution is necessary when using simultaneous inhibitors (for example, Erythromycin , Fluoxetine , gemfibrozil) or inducers (for example, rifampicin, Carbamazepine , iferenzine, fumexetine, gemfibrozil) or inducers (for example, rifampicin, carbamazepine, cefampicin, gemfibrozil). ) isoenzymes of the cytochrome P450 system.

Inhibitors of microsomal oxidation (includingketoconazole, cimetidine, Verapamil , diazepam, quinidine, cyclosporin) inhibit the metabolism of paclitaxel. However, it is known that while taking Ketoconazole and paclitaxel at the same time, the elimination of the latter does not slow down, so both drugs can be used without dose adjustment.

With simultaneous use of paclitaxel and nelfinavir or ritonavir (but not indinavir), the systemic clearance of paclitaxel is significantly reduced. There is not enough information about the interaction of paclitaxel and other protease inhibitors with simultaneous use.

Polyoxyethylated castor oil, which is part of paclitaxel, can cause the extraction of di- (2-hexyl) phthalate (DEHP) from plasticized PVC containers, and the degree of leaching of DEHP increases with increasing solution concentration and time. Therefore, in the preparation, storage and administration of Paclitaxel-Ebeve drug, use equipment that does not contain PVC parts.

The drug is available on prescription.

The drug should be stored out of the reach of children, protected from light at a temperature not higher than 25 ° C.