Carboplatin-LENS, 10 mg/ml 15 ml

Pharmacodynamics

An alkylating antitumor agent containing platinum. Mechanism of action is associated with formation of cross-links between neighboring pairs of guanine bases in DNA, which leads to suppression of nucleic acid biosynthesis and cell death.

Pharmacokinetics

Metabolized by hydrolysis to form active compounds that interact with DNA. Binding to proteins is very low. However, platinum formed from carboplatin binds irreversibly to plasma proteins and is slowly excreted with a minimum T_1/2 of 5 days.

The T_1/2 of carboplatin is 1.1-2 h in the initial phase and 2.6-5.9 h in the final phase. Renal excretion is 71% within 24 hours with a CK of 60 ml/min or more.

Indications

Active ingredient

Composition

1 ml (1 vial) contains:

Active ingredients:

carboplatin 10 mg (150 mg).

How to take, the dosage

Carboplatin-LNS can be used both as monotherapy and in combination with other antitumor drugs. Special literature should be used when choosing the dose and regimen in each individual case.

The drug is administered intravenously in the following dosage regimens:

The administration of Carboplatin-LNS is repeated at intervals of at least 4 weeks with platelet counts of at least 100,000 cells/mm3 blood and neutrophils of at least 2000 cells/mm3 blood.

Fluid administration before or after administration of Carboplatin-LENS, as well as forced diuresis is not required.

Depending on bone marrow status or renal function, the therapeutic dose of Carboplatin-LNS may be adjusted as follows:

Patients with risk factors, such as after myelosuppressive therapy or with low functional status (ECOG-Zubrod 2-4 or Karnofsky score below 80%)

The initial dose should be reduced by 20-25%.

Patients over 65 years of age

Initial and subsequent doses may need to be adjusted.

For patients with symptoms of moderate or severe hematologic toxicity (i.e., platelet and neutrophil counts less than 50000 and 500/mm3 respectively)

A 25% dose reduction – both in monotherapy and in combination treatment regimens – should be considered.

Patients with impaired renal function (creatinine clearance less than 60 mL/min)

Due to the increased risk of severe myelosuppression, the dose of Carboplatin-LNS is reduced as follows:

Interaction

In concomitant use with drugs with myelodepressant and nephrotoxic effects, mutual intensification of toxic effects is possible.

Special Instructions

Caution should be exercised when bone marrow hematopoiesis is inhibited (including concomitant radiation or chemotherapy), prior therapy with nephrotoxic drugs (e.g., cisplatin), hearing disorders, acute infections of viral, fungal or bacterial nature, in patients with ascites or exudative pleurisy, postvaccination period.

Caution should be exercised when using carboplatin in patients after radiation therapy.

Carboplatin should only be used under the supervision of a physician experienced in chemotherapy. Renal function, peripheral blood count, neurological status, audiometry should be monitored before and during treatment. There may be changes in biochemical parameters: increased serum levels of urea and creatinine, decreased concentration of magnesium, potassium, calcium.

The administration of carboplatin is not recommended for vaccination of patients or their families.

Contraindications

Side effects

Hematopoietic system disorders: inhibition of medullary hematopoiesis.

Digestive system disorders: nausea, vomiting, stomatitis, diarrhea or constipation, abdominal pain, decreased appetite, liver function disorders (increased AST, ALP activity and bilirubin concentration in blood serum).

Nervous system disorders: Asthenia, peripheral polyneuropathy (paresthesias, decreased deep tendon reflexes), decreased visual acuity up to complete loss of vision or loss of ability to distinguish colors (improvement or complete recovery of vision usually occurs within weeks after stopping the drug; cortical blindness was observed in patients with impaired renal function treated with high doses of carboplatin), hearing loss, tinnitus; long-term therapy may lead to cumulative neurotoxicity.

Urinary system disorders: increased serum creatinine and urea concentrations (acute renal damage has rarely been observed; the risk of nephrotoxicity with carboplatin increases with increasing doses of carboplatin and in patients who were previously treated with cisplatin).

The sexual system: azoospermia, amenorrhea.

Water-electrolyte balance: hypokalemia, hypocalcemia, hyponatremia and hypomagnesemia.

Allergic reactions: erythematous rash, fever, pruritus, urticaria, bronchospasm, decreased blood pressure, anaphylactoid reactions, allergic reactions at the injection site; rarely – exfoliative dermatitis.

Others: changes in taste, alopecia, flu-like symptoms (fever, fever), hemolytic-uremic syndrome, myalgia/arthralgia, heart failure, cerebrovascular disorders.

Overdose

Symptoms: increased adverse reactions.

Treatment: specific antidotes used in case of carboplatin overdose are unknown. Treatment is symptomatic. Hemodialysis may be used in the first 3 hours after drug administration.

Pregnancy use

The use is contraindicated in pregnancy and during lactation (breastfeeding).

Women of childbearing age receiving carboplatin therapy should use reliable contraceptive measures.

In experimental studies, carboplatin has been shown to have teratogenic and embryotoxic effects.