Composition, form of production and packaging
Lyophilized powder for the preparation of a solution for intravenous administration in white.
1 f.
carboplatin 50 mg
Excipients: mannitol.
Vials (1) - cardboard boxes.
Lyophilized powder for the preparation of a solution for intravenous administration in white.
1 f.
carboplatin 150 mg
Excipients: mannitol.
Vials (1) - cardboard boxes.
Lyophilized powder for the preparation of a solution for intravenous administration in white.
1 f.
carboplatin 450 mg
Excipients: mannitol.
Vials (1) - cardboard boxes.
The solution for intravenous administration is clear, colorless or slightly yellow in color.
1 ml of 1 fl.
carboplatin 10 mg 50 mg
Auxiliary substances: mannitol, water d / and.
5 ml - bottles (1) - cardboard boxes.
The solution for intravenous administration is clear, colorless or slightly yellow in color.
1 ml of 1 fl.
carboplatin 10 mg 150 mg
Auxiliary substances: mannitol, water d / and.
15 ml - bottles (1) - cardboard boxes.
The solution for intravenous administration is clear, colorless or slightly yellow in color.
1 ml of 1 fl.
carboplatin 10 mg 450 mg
Auxiliary substances: mannitol, water d / and.
45 ml - bottles (1) - cardboard boxes.
INSTRUCTION FOR THE SPECIALIST.
The product description was approved by the manufacturer for the 2009 print edition.
PHARMACHOLOGIC EFFECT
Carboplatin is an inorganic complex compound containing heavy metal - platinum.
It is suggested that the main mechanism of action of this drug is due to binding to DNA, resulting in the formation of predominantly intra-spiral crosslinks, which alter the structure of DNA and suppress its synthesis. This effect manifests itself regardless of the phase of the cell cycle. Hydration of carboplatin, as a result of which the active form (form) of the drug is formed, is slower than hydration of cisplatin.
PHARMACOKINETICS
After a single injection of carboplatin in the form of an IV infusion for 1 hour, the plasma concentration of total platinum and free (ultrafiltration) platinum decreases in accordance with the two-phase model of kinetics of the first order. The initial T 1/2 of free platinum is about 1-2 hours, and the terminal T 1/2 is 3-6 hours; total platinum is characterized by a similar initial T 1/2 , but the terminal T 1/2 is longer (about 24 h). With repeated administration of the dose for four days in a row, there is no accumulation of platinum in the plasma. At 24 hours after dosing, more than 85% of platinum in the plasma is in the protein-bound state.
Carboplatin is excreted mainly by the kidneys, and about 30% of the administered dose is excreted unchanged. In patients with CC, equal to 60 ml / min or more, approximately 65% ​​and 70% of the administered dose are excreted for 12 and 24 hours after administration, respectively. Since carboplatin is excreted almost entirely by glomerular filtration, only a very small concentration of carboplatin is present in the renal tubules, which may explain the small nephrotoxic potential of the drug compared to cisplatin.
INDICATIONS
Treatment of the following solid tumors:
ovarian cancer;
- germinogenic tumors of men and women;
- lung cancer;
- cervical cancer;
- Head and neck tumors;
osteogenic sarcomas;
- medulloblastoma.
DOSING MODE
Carboplatin can be used as a monotherapy or in combination with other antitumor drugs. The drug is administered IV in the following dose regimens:
- 300 - 400 mg / m 2 IV drip for 15-60 minutes or as a 24-hour infusion;
- 100 mg / m 2 IV drip for 15-60 minutes daily for 5 days.
Carboplatin administration is repeated at intervals of not less than 4 weeks with platelet counts of at least 100,000 cells / mm 3 of blood and neutrophils of at least 1500 cells / mm 3 of blood.
The introduction of liquid before or after the application of carboplatin, as well as forced diuresis is not required.
Depending on the state of the bone marrow or kidney function, the therapeutic dose of carboplatin can be corrected as follows:
- for patients who have symptoms of moderate or severe hematologic toxicity (ie, the number of platelets and neutrophilic leukocytes is less than 50,000 and 500 / mm 3, respectively), the possibility of dose reduction should be considered - in both monotherapy and combined treatment regimens - by 25%;
- In patients with symptoms of impaired renal function (CC <60 ml / min), the risk of toxic effects of carboplatin increases, so the dose of carboplatin should be reduced as follows:
Creatinine clearance (ml / min) The recommended dose of carboplatin (mg / m 2 )
41-59 250
16-40 200
In the presence of risk factors, such as, for example, previous courses of myelosuppressive therapy and / or age over 65 years, a dose reduction of 20-25% is recommended; Careful use of carboplatin is also recommended if the patient has previously been treated with nephrotoxic drugs, such as cisplatin.
Before use, the solution of carboplatin must be visually inspected for mechanical inclusions and discolouration. Dilute carboplatin should be in physiological saline or 5% glucose solution until a concentration of 1-0.5 mg / ml is reached immediately before use - infusion should be performed no more than 24 hours after the preparation of the solution.
SIDE EFFECT
From the hemopoietic system: the main toxic factor limiting the dose of carboplatin is the suppression of bone marrow hematopoiesis. Myelosuppression is dose-dependent. The lowest level of platelets and white blood cells / granulocytes is usually achieved 2-3 weeks after the start of the drug, with thrombocytopenia occurring more often. Adequate recovery to the level that allows the next dose of carboplatin, usually takes at least 4 weeks. A sufficiently large number of patients may also exhibit symptoms of anemia (a hemoglobin level of less than 11 g / dl), the intensity of which depends on the total dose of the drug. It may be necessary to perform transfusion therapy, especially in patients undergoing long-term treatment (for example, more than 6 cycles of drug administration). There is also the possibility of clinical complications such as fever, infectious diseases, sepsis / septic shock and bleeding.
From the digestive tract: within 6-12 hours after taking the drug, there is a possibility of nausea and / or vomiting (from mild to moderate), lasting up to 24 hours or more. The risk of emetic effects can be reduced by pre-therapy with antiemetics, continuous intravenous infusion of carboplatin for 24 hours or a fractional dose for 5 consecutive days. Also in a number of cases, other types of unwanted effects on the digestive tract, such as inflammation of the oral mucosa, diarrhea, constipation and abdominal pain were observed.
From the side of the central nervous system and peripheral nervous system: there is a possibility of peripheral neuropathy, mainly in the form of paresthesia and reduction of deep tendon reflexes, which is more likely in patients older than 65 years with prolonged or previous treatment with cisplatin. It is also possible the appearance of symptoms of a violation of the central nervous system. Long-term therapy with the drug may lead to cumulative neurotoxicity.
From the side of the hearing: ototoxicity manifests itself in the form of noise in the ears and hearing impairment.
From the side of the eyes: there is a possibility of temporary deterioration or complete loss of vision (possible loss of the ability to distinguish colors and see light), as well as other violations of visual function. Improvement and / or complete restoration of vision, usually occurs within a few weeks after discontinuation of the drug. In patients with impaired renal function, treated with high doses of carboplatin, cortical blindness was observed.
From the kidneys: there may be a slight and temporary increase in the concentrations of creatinine and urea in the blood serum. Acute kidney damage was rare. The risk of nephrotoxicity when taking carboplatin (a decrease in creatinine clearance) increases with an increase in the dose of carboplatin, as well as in patients who have previously been treated with cisplatin.
From the side of the liver: there may be a slight and, as a rule, a temporary increase in the concentrations of ACT, bilirubin and alkaline phosphatase in the blood serum. In patients treated with high doses of carboplatin with autologous bone marrow transplantation, significant impairment of liver function was observed.
From the electrolyte balance: hypokalemia, hypocalcemia, hyponatremia and / or hypomagnesemia are possible.
Allergic reactions: erythematous rash, fever, itching, urticaria, bronchospasm, arterial hypotension and anaphylactic reactions. These reactions can occur only a few minutes after the administration of carboplatin. In rare cases, exfoliative dermatitis may also occur.
Other side effects: alopecia, asthenia, influenza-like symptoms, hemolytic-uremic syndrome, myalgia / arthralgia, heart failure, cerebrovascular disorders and allergic reactions directly at the site of injection.
CONTRAINDICATIONS
- severe renal dysfunction;
- expressed myelosuppression;
- profuse bleeding;
- pregnancy and the period of breastfeeding;
- Hypersensitivity to carboplatinum or other platinum-containing compounds.
PREGNANCY AND LACTATION
Contraindication: pregnancy and the period of breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
in patients with symptoms of impaired renal function (CC <60 mL / min), the risk of toxic effects of carboplatin increases, so the dose of carboplatin should be reduced as follows:
Creatinine clearance (ml / min) The recommended dose of carboplatin (mg / m 2 )
41-59 250
16-40 200
APPLICATION IN ELDERLY PATIENTS
In the presence of risk factors, such as, for example, age over 65 years, a dose reduction of 20-25% is recommended.
SPECIAL INSTRUCTIONS
The administration of carboplatin should be carried out under the supervision of a physician with experience in the use of cytotoxic drugs. Constant monitoring of possible toxic effects in the treatment with carboplatin is mandatory, especially when using high doses of the drug.
Do not use for preparation and administration of the preparation containing aluminum needles, syringes, catheters and infusion systems. Aluminum can react with carboplatin, resulting in a precipitate or loss of activity of the drug.
Patients should regularly (for example, once a week) count the formed elements of peripheral blood and monitor kidney function (the most sensitive indicator is QC).
Periodically, it is recommended to perform neurologic examinations, especially in patients previously treated with cisplatin and in patients older than 65 years.Carboplatin can cause cumulative ototoxic effects. Audiographic examinations should be conducted before and during treatment or in case of symptoms of hearing impairment. In the case of a clinically significant impairment of the hearing function, an appropriate dose change or discontinuation of treatment may be required.
Women and men should be treated with carboplatin and within 3 months after the use of reliable methods of contraception.
If the product gets into the eyes, they must be washed immediately with a large amount of water or a solution of sodium chloride. In case of contact with the skin, immediately contact the product with plenty of water. If the product is inhaled or if it gets into the mouth, immediately consult a doctor.
OVERDOSE
There are no special antidotes used in case of carboplatin overdose. In case of overdose, the more severe adverse reactions listed above should be expected. Treatment is symptomatic. In the first 3 hours after the administration of the drug, the use of hemodialysis is possible.
DRUG INTERACTION
The use of carboplatin in combination with other myelosuppressive drugs or radiotherapy can increase the risk of hematological toxicity.
The use of carboplatin in combination with aminoglycosides, as well as with other nephrotoxic drugs increases the risk of nephrotoxic and / or ototoxic effects.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Keep out of the reach of children at room temperature 15-25 В° C. Protect from light. Shelf life for the solution is 2 years, for lyophilized powder 50 mg and 450 mg for 3 years, 150 mg for 4 years.
