Composition, form of production and packaging
Concentrate for the preparation of a solution for infusions in the form of a clear, colorless or pale yellow solution.
1 ml
carboplatin 10 mg
Auxiliary substances: water d / u - up to 1 ml.
15 ml - bottles of glass (1) - packs of cardboard.
Concentrate for the preparation of a solution for infusions in the form of a clear, colorless or pale yellow solution.
1 ml
carboplatin 10 mg
Auxiliary substances: water d / u - up to 1 ml.
45 ml - bottles of glass (1) - packs of cardboard.
Concentrate for the preparation of a solution for infusions in the form of a clear, colorless or pale yellow solution.
1 ml
carboplatin 10 mg
Auxiliary substances: water d / u - up to 1 ml.
5 ml - bottles of glass (1) - packs of cardboard.
Concentrate for the preparation of a solution for infusions in the form of a clear, colorless or pale yellow solution.
1 ml of 1 fl.
carboplatin 10 mg 600 mg
Auxiliary substances: water d / u - up to 1 ml.
60 ml - glass bottles (1) - packs of cardboard.
Concentrate for the preparation of a solution for infusions in the form of a clear, colorless or pale yellow solution.
1 ml
carboplatin 10 mg
Auxiliary substances: water d / u - up to 1 ml.
15 ml - bottles of glass (1) - packs of cardboard.
Concentrate for the preparation of a solution for infusions in the form of a clear, colorless or pale yellow solution.
1 ml
carboplatin 10 mg
Auxiliary substances: water d / u - up to 1 ml.
45 ml - bottles of glass (1) - packs of cardboard.
Concentrate for the preparation of a solution for infusions in the form of a clear, colorless or pale yellow solution.
1 ml of 1 fl.
carboplatin 10 mg 600 mg
Auxiliary substances: water d / u - up to 1 ml.
60 ml - glass bottles (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
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
The pharmacokinetics of carboplatin is a complex process and involves transformations of the parent carboplatin, total platinum and platinum, which is amenable to ultrafiltration. The total platinum consists of protein-bound and protein-unbound platinum, while platinum, amenable to ultrafiltration, consists of carboplatin and protein-unbound carboplatin metabolites. In pharmacokinetic studies of carboplatin, the level of platinum that is amenable to ultrafiltration is usually measured, as only platinum, not bound to proteins or its metabolites containing platinum, is usually cytotoxic.
After a single administration of carboplatin in the form of an IV infusion of Cmax carboplatin, total platinum and platinum capable of ultrafiltration, almost immediately. Platinum is distributed in all tissues and body fluids, with the highest concentrations being observed in the tissues of the kidneys, liver, skin and tumor tissues. The initial T 1/2 of carboplatin, the total platinum and platinum, which is amenable to ultrafiltration, are almost identical when administered intravenously; T 1/2carboplatin is 1-2 hours. Actually carboplatin with proteins does not bind, but decomposes to products containing platinum, which very quickly bind to proteins.During the first 4 hours after carboplatin administration, less than 24% of platinum binds to plasma proteins; After 24 hours, the amount of bound platinum is 87%.
The concentration of carboplatin and platinum, amenable to ultrafiltration, is reduced in accordance with the two-phase model. The concentration of total platinum is reduced in accordance with the three-phase model. With normal renal function, T 1/2 of carboplatin and platinum, amenable to ultrafiltration, are 2-3 hours. The final T1/2 of the total platinum is 4-6 days.
Carboplatin and its platinum-containing metabolites are mainly excreted in the urine. With normal kidney function, about 65% of the dose of carboplatin is excreted in the urine for 12 hours; after 24 hours, 71% of the dose is withdrawn. A significant part is derived in the form of unchanged carboplatin. Carboplatin (in the form of carboplatin, amenable to ultrafiltration) is effectively eliminated by hemodialysis.
In urine, after 24 hours, all platinum is present in the form of carboplatin. Only 3-5% of the administered platinum is excreted in the urine in the period 24-96 hours.
Since carboplatin is excreted almost entirely through 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
ovarian cancer;
- germinogenic tumors of men and women;
- lung cancer;
- cervical cancer;
- malignant tumors of the head and neck;
- Transitional cell cancer of the bladder.
DOSING MODE
Paract can be used both in the form of monotherapy, and in combination with other antitumor drugs. When choosing a dose and treatment in each individual case, you should use special literature.
The drug is administered intravenously in the following dose doses:
- 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;
Introduction The parake is repeated at intervals of not less than 4 weeks with platelet counts of at least 100,000 cells / ОјL of blood and neutrophils of at least 2,000 cells / ОјL of blood at the time of the next administration.
The introduction of liquid before or after the application of the Paracta, as well as the achievement of forced diuresis is not required.
Depending on the condition of the bone marrow or the function of the kidneys, the therapeutic dose of Paract can be corrected as follows:
- With a decrease in the number of platelets to 50,000 / ОјL and / or neutrophils to 500 / Ојl, no dose adjustment is required for previous carboplatin therapy.
- For the observed minimum platelet counts of less than 50,000 / ОјL and / or neutrophils less than 500 / Ојl, the previous course of carboplatin therapy should consider reducing the next dose by 25% in both monotherapy and combined treatment regimens.
- In case of kidney failure (CC less than 60 ml / min), the risk of toxic effects of carboplatin increases, and therefore recommended doses of carboplatin are at creatinine clearance of 41-59 ml / min - 250 mg / m 2 , with creatinine clearance of 16-40 ml / min - 200 mg / m 2 .
- Patients with risk factors such as previous courses of myelosuppressive therapy, age over 65 years, low functional status (ECOG-Zubrod 2-4 or Karnovsky score below 80%) are recommended to reduce the initial dose of carboplatin by 20-25% .
Determination of the dose by the formula
The initial dose of the drug in milligrams can be determined from the Calvert formula, which describes the dependence of the glomerular filtration rate (GFR in ml / min) and the desired drug concentration on time (AUC in mg / ml x min):
Total dose (mg) = AUC x (GF + 25)
Desirable value of AUC Planned chemotherapy with carboplatin The patient's status in relation to treatment
5-7 mg / ml.min Monotherapy Previously untreated
4-6 mg / ml. Monotherapy Previously treated
4-6 mg / ml.min In combination with cyclophosphamide Previously untreated
Rules for the preparation of a solution for infusions
Before administration, the drug is diluted to a concentration of 0.5 mg / ml with 5% dextrose solution or 0.9% sodium chloride solution.
Dilute drug solutions are stable for 8 hours at 25 В° C and for 24 hours when stored in a refrigerator at 4 В° C.
SIDE EFFECT
On the part of the organs of hematopoiesis: 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 a 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.
On the part of the digestive system: nausea, vomiting (can be prevented by the prescription of antiemetics, continuous intravenous infusion of carboplatin for 24 hours or fractional dose administration for 5 consecutive days), stomatitis, diarrhea or constipation, abdominal pain, decreased appetite, impaired liver function (increased activity of AST, APF and serum bilirubin concentration).
From the side of the central nervous system: asthenia, peripheral polyneuropathy (paresthesia, reduction of deep tendon reflexes), reduced visual acuity up to complete loss of vision or loss of ability to discern color (improvement 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), hearing loss, tinnitus. Long-term therapy with the drug may lead to cumulative neurotoxicity.
On the part of the genitourinary system: increased concentrations of creatinine and urea in the blood serum (acute kidney damage was rare, the risk of nephrotoxicity when taking carboplatin increases with an increase in the dose of carboplatin, as well as in patients who had previously been treated with cisplatin), azoospermia, amenorrhea.
From the side of the water-electrolyte balance : hypokalemia, hypocalcemia, hyponatremia and hypomagnesemia.
Allergic reactions: erythematous rash, fever, pruritus, urticaria, bronchospasm, lowering of arterial pressure, anaphylactoid reactions, allergic reactions at the injection site. Rarely - exfoliative dermatitis.
Other: changes in taste, alopecia, influenza-like symptoms (fever, fever), hemolytic-uremic syndrome, myalgia / arthralgia, heart failure, cerebrovascular disorders.
CONTRAINDICATIONS
- hypersensitivity to carboplatinum or other platinum-containing compounds;
- severe renal dysfunction;
- expressed myelosuppression;
- profuse bleeding;
- pregnancy and the period of breastfeeding;
- Children's age (effectiveness and safety is not well understood).
With caution: with oppression of bone marrow hematopoiesis (including against concomitant radiation or chemotherapy), previous therapy with nephrotoxic drugs (eg cisplatin), hearing impairment, acute infectious diseases of viral, fungal or bacterial nature, post-vaccination period.
PREGNANCY AND LACTATION
The drug is contraindicated during pregnancy and during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
The drug is contraindicated in severe impairment of kidney function.
APPLICATION FOR CHILDREN
The drug is contraindicated in childhood.
APPLICATION IN ELDERLY PATIENTS
Elderly patients (over 65 years) are recommended to reduce the initial dose of the drug by 20-25%.
SPECIAL INSTRUCTIONS
Treatment Paractom should be carried out under the supervision of a doctor who has experience in the use of cytotoxic drugs.
Do not use needles, syringes, catheters and infusion systems containing aluminum that can react with carboplatin, resulting in a precipitate or loss of activity of the preparation.
Regularly (for example, once a week) to count the formed elements of peripheral blood and monitor kidney function (the most sensitive indicator is the creatinine clearance).
Periodically, it is recommended to perform neurologic examinations, especially in patients who have previously been treated with cisplatin, and in patients older than 65 years.
Since Paract can cause cumulative ototoxic effects, patients are advised to perform audiographic studies before and during treatment. 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 during treatment Paracette should use reliable methods of contraception.
When applying the Paracta, all the usual instructions adopted for the use of cytotoxic drugs should be observed.
During treatment, patients are not recommended to be vaccinated.
OVERDOSE
Special antidotes used in case of carboplatin overdose are unknown. 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 aminiklikozidami, 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
At a temperature of no higher than 25 В° C. Keep out of the reach of children.
Shelf life is 18 months. Do not use the product after the expiration date printed on the package.
