Carboplatin-Teva lyophilisate for preparation of solution 450mg No. 1 bottle
Carboplatin-Teva lyophilisate for preparing solution 450mg No. 1 bottle
PharmacologyPharmacological action - antitumor, alkylating, cytostatic, immunosuppressive.
Bifunctionally alkylates DNA strands, cross-interacts with inter-stalk hydrogen bonds, which leads to disruption of DNA matrix function, long-term non-specific suppression of nucleic acid biosynthesis and cell death. Causes stunting and reversing the development of many types of tumors. Regression of primary tumors and metastases is associated with the effect of "platinization" on the body's immune system. When using a combination of cisplatin - cyclophosphamide and carboplatin - cyclophosphamide in the treatment of patients with stage III-IV ovarian cancer, the objective effect was 50–75% and 59–61%, respectively, with equal life expectancy. With long-term use, a long-term effect is possible - the development of secondary malignant tumors, degenerative changes in the sex glands, leading to amenorrhea or azo-spermia, reduced fertility. In experimental studies in vivo and in vitro, it exhibits mutagenic, embryotoxic and teratogenic properties.
After i / v administration (300–500 mg / m2) with creatinine Cl about 60 ml / min and higher, the plasma concentration decreases in two phases: the duration of the first phase — 1.1–2 h, the second — 2.6–5.9 h An increase in plasma concentration as a function of dose and AUC is described by linear pharmacokinetics. Clearance, volume of distribution and average circulation time in the blood are 4.4 l / h, 16 l and 3.5 h, respectively. Almost does not bind to plasma proteins, but platinum released from carboplatin irreversibly binds to proteins, and its T1 / 2 is 5 days. Subjected to hydrolysis with the formation of active compounds that interact with DNA molecules. The main route of elimination is renal excretion; with creatinine clearance values of 60 ml / min and above, 65% of the dose is excreted in the urine within 12 hours, and within 24 hours - 71% and only 3-5% of platinum is released within 24–96 hours. In case of impaired renal function and elderly people (probably a decrease in renal filtration), adjustment of the dosage regimen and dose reduction are necessary, since cumulation and an increase in the time of exposure to the bone marrow are possible (for example, with AUC 4–5 mg / ml / min, thrombocytopenia and leukopenia are 16 and 13%, respectively, with AUC 6–7 mg / ml / min - 33 and 34%).
Use of the substance CarboplatinOvarian cancer, germ cell tumors in men and women, small-cell and non-small cell lung cancer, malignant neoplasms of the head and neck, cervical and uterine, breast cancer, bladder cancer, soft tissue sarcoma, melanoma.
ContraindicationsHypersensitivity (including to other drugs containing platinum), clinical signs of bleeding (including from tumor tissue), severe renal impairment, marked myelosuppression.
Restrictions on the use ofEstimation of the risk-benefit ratio is necessary when prescribing in the following cases: chicken pox, shingles and other systemic infections, renal dysfunction, hearing loss, ascites or exudative pleurisy, bone marrow suppression, previous cytotoxic or radiation therapy, elderly (over 65 years old) and children's age.
Use during pregnancy and lactationContraindicated in pregnancy.
Category of action on the fetus by the FDA - D.
At the time of treatment should stop breastfeeding.
Side Effects of CarboplatinOn the part of the digestive tract: a change in taste, anorexia, nausea, vomiting (65%), abdominal pain (17%), constipation and / or diarrhea (6%), gastrointestinal bleeding, impaired liver function (the severity increases with metastatic lesions ), stomatitis, inflammation of the oral mucosa.
On the part of the nervous system and sensory organs: peripheral neuropathy (6%), changes in the nervous system (5%), asthenia, convulsive syndrome, in 1% - a decrease in the severity of hearing and vision.
From the side of cardiovascular system and blood (blood formation, hemostasis): myelodepression: thrombocytopenia below 100 &№183; 109 / l - 90%, below 50 &№183; 109 / l - 25%, leukopenia below 4 &№183; 109 / l - 67%, below 2 &№183; 109 / l - 15%, neutropenia below 2 &№183; 109 / l - 74%, below 1 &№183; 109 / l - 16%, anemia (hemoglobin level below 11 g / dl) - 71%, less than in 1% of cases - heart failure, embolism, cerebrovascular disorders; bleeding and hemorrhage, hypotension.
On the part of the respiratory system: cough, shortness of breath, bronchospasm.
On the part of the genitourinary system: impaired renal function, painful, difficulty urinating, hematuria, amenorrhea, azoospermia.
For the skin: alopecia (3%), in 2% of cases, allergic reactions (rash, itching, etc.).
Metabolism: hypomagnesemia (29%), changes in sodium concentration (29%), hypocalcemia (22%), hypokalemia (20%), increased alkaline phosphatase activity (24%), AST level (15%), urea (14 %), creatinine (6%), total bilirubin (5%), decreased creatinine clearance.
Other: pain syndrome (back pain, side), infection, hyperthermia, chills, anaphylactoid reactions.
InteractionPharmaceutically incompatible with aluminum salts (during the interaction, the formation of a precipitate is observed, leading to a decrease in effectiveness). Enhances (mutually) nephrotoxicity of propranolol, aminoglycosides, as well as the effects of other drugs that have nephrotoxic, neurotoxic, ototoxic and myelusuppressive effects. Impairs the effectiveness of immunization with inactivated vaccines; when using vaccines containing live viruses, enhances the replication of the virus and the side effects of vaccination. There is cross-resistance with cisplatin, enhances the neurotoxic and ototoxic effects caused by this drug previously (observed in 30% of patients). Other myelotoxic drugs, radiation therapy increase bone marrow depression (potentiate neutropenia, thrombocytopenia).
OverdoseSymptoms: nausea, vomiting, severe bone marrow depression, hepatotoxicity, bleeding.
Treatment: hospitalization, monitoring of vital functions; symptomatic therapy; if necessary - transfusion of blood components, the appointment of broad-spectrum antibiotics.
Dosage and administrationIn / in, the dose is selected individually, depending on the indications and the stage of the disease, the scheme of antitumor therapy, adjusted based on the clinical effect, the severity of toxic action. With the previous treatment of myelosuppressive drugs, in patients with initial hypofunction of bone marrow hematopoiesis, the general serious condition of the dose is reduced by 20-25%. In the event of impaired renal function, the dose of carboplatin is adjusted in accordance with creatinine clearance.
Precautions substances carboplatinApplication is possible only under the supervision of a physician with experience chemotherapy. Adequate measures should be provided for the diagnosis and treatment of possible complications, including relief of anaphylactic reactions (adrenaline, oxygen, antihistamines, corticosteroids, etc.). Before and during treatment (with small intervals), it is necessary to determine the level of hemoglobin or hematocrit, urea nitrogen, bilirubin, creatinine clearance, leukocyte count (total, differential), platelets, AST activity, potassium, magnesium, sodium, calcium concentrations, total neurological examination, including audiometry.Due to the development of cumulative action, treatment should be carried out no more than 1 time in 4 weeks (the recovery time of the bone marrow function), the number of platelets should be more than 100 &№183; 109 / l, leukocytes 2 &№183; 109 / l. The lowest level of leukocytes and platelets is observed 2-3 weeks after administration. Recovery to the level that allows the introduction of the next dose of carboplatin, as a rule, takes at least 4 weeks.
Adjustment of the dosing regimen is necessary in patients over 65 years of age (a 10% increase in the risk of developing peripheral neuropathy), in patients with existing impaired renal function (depending on creatinine clearance) or when combined with other chemotherapeutic drugs.
Nausea and vomiting develop 6–12 hours after drug administration and continue for 24 hours (antiemetics must be prescribed). The development of allergic reactions occurs within a few minutes after administration. The ototoxic effect is manifested by lowering the threshold of audibility in the upper frequencies. If the following symptoms appear: chills, fever, cough or hoarseness, pain in the lower back or side, painful or difficult urination, bleeding or hemorrhage, black stools, blood in the urine or feces - you should immediately consult with your doctor. In the event of thrombocytopenia, extreme caution is recommended when performing invasive procedures, regular inspection of IV sites, skin and mucous membranes (to detect signs of bleeding), limiting the frequency of venipuncture and refusal of intramuscular injections, monitoring blood content in urine, vomitus, kale. Such patients need to shave with care, do a manicure, brush their teeth, use dental floss and toothpicks, perform dental procedures; It is necessary to prevent constipation, avoid falls and other injuries, as well as alcohol and acetylsalicylic acid, which increase the risk of gastrointestinal bleeding. The vaccination schedule should be postponed (to be carried out no earlier than 3 months to 1 year after the completion of the last course of chemotherapy) to the patient and other family members living with him (it is necessary to refuse immunization with oral polio vaccine). Avoid contact with infectious patients or use non-specific measures for prophylaxis (face shield, etc.).It should refrain from use in pediatric practice, since the safety and effectiveness of its use in children has not been determined. During treatment, it is necessary to use adequate contraceptive measures. In case of contact with the skin or mucous membranes, wash thoroughly with water (mucous membranes) or with soap and water (skin). Dissolution, dilution and administration of the drug is carried out by trained medical personnel in compliance with protective measures (gloves, masks, clothing, etc.).
It is a drug. Consultation with a doctor is required.