Release form, packaging, and composition of the drug Cymeven®

Lyophilisate for solution for infusion in the form of a porous mass compacted into a tablet, sometimes in the form of separate parts of the tablet, white or almost white; The reconstituted solution is a clear or slightly opalescent, colorless, or slightly yellowish liquid.

Clinico-pharmacological group: Antiviral drug

Pharmaco-therapeutic group: Antiviral agent

Pharmacokinetics

Suction

After infusion of ganciclovir at a dose of 5 mg/kg for 1 hour to HIV- and CMV-infected patients or adult patients with AIDS, the total area under the concentration-time curve (AUC0-24) ranges from 21.4 ± 3.1 to 26.0 ± 6.06 μg x hour /ml The maximum concentration of the drug in plasma (Cmax) ranged from 7.59±3.21 and 8.27±1.02 to 9.03±1.42 µg/ml.

Distribution

The volume of distribution of ganciclovir after intravenous administration correlates with body weight and, upon reaching an equilibrium concentration, is 0.5-0.8 l / kg. The concentration of the drug in the cerebrospinal fluid is 0.25-5.67 hours after intravenous administration of ganciclovir at a dose of 2.5 mg/kg every 8 or 12 hours is 24-67% of plasma concentrations and is equal to 0.50-0.68 mcg/ml. Communication with plasma proteins – 1-2%.

Metabolism and excretion

After intravenous administration at doses of 1.6 to 5.0 mg/kg, the kinetics of ganciclovir is linear. The main route of elimination is renal excretion of unchanged drugs by glomerular filtration and tubular secretion. In patients with normal renal function, 89.6 ± 5.0% of the intravenously administered dose of ganciclovir is found in the urine unchanged. In individuals with normal renal function, systemic clearance ranges from 2.64±0.38 to 4.52±2.79 ml/min/kg, and renal clearance ranges from 2.57±0.69 to 3.48±0.68 ml/min/kg, which corresponds to 90-101% of the administered ganciclovir. The elimination half-life in persons without renal insufficiency ranges from 2.73 ± 1.29 to 3.98 ± 1.78 hours.

Pharmacokinetics in special groups of patients

kidney disease

Hemodialysis reduces plasma concentrations of ganciclovir after intravenous and oral administration at doses of 1.25-5.0 mg/kg by approximately 50%.

When using an intermittent hemodialysis regimen, the clearance rates of ganciclovir range from 42 to 92 ml/min, and the half-life of the drug during dialysis is 3.3-4.5 hours. With continuous dialysis, the clearance of ganciclovir was lower (4.0-29.6 ml/min), but in the period until the next dose of the drug, a larger percentage of the dose was removed from the body. With intermittent hemodialysis, the fraction of ganciclovir removed in one session of hemodialysis ranges from 50% to 63%.

Elderly patients

Studies have not been conducted on persons over 65 years of age.

Indications for Cymeven®

  • treatment of life-threatening or vision-threatening overt CMV infection in people with immunodeficiencies, including AIDS;
  • prevention of overt CMV infection in patients after organ transplantation.

Dosing regimen

Adults and children over 12 years old

The standard dosage for the treatment of CMV retinitis

Initial therapy: IV infusion at a dose of 5 mg/kg of body weight for 1 hour, every 12 hours (10 mg/kg/day) for 14-21 days (for patients with normal renal function).

Maintenance therapy: 5 mg/kg by intravenous infusion over 1 hour, daily for 7 days a week or 6 mg/kg daily for 5 days a week.

Contraindications for use

the absolute number of neutrophils is less than 500 cells in 1 μl or the number of platelets is less than 25,000 cells in 1 μl or the hemoglobin level is less than 8 g / dl;

children’s age up to 12 years;

hypersensitivity to ganciclovir, valganciclovir, or any other component of the drug.

due to the similarity in the chemical structure of ganciclovir, aciclovir, and valaciclovir, cross-hypersensitivity reactions between these drugs are possible.

With caution, renal failure.

Use during pregnancy and lactation

Category C drug (according to the FDA classification – U.S. Food and Drug Administration).

During treatment with ganciclovir, women of childbearing age should be advised to use reliable methods of contraception. Men are advised to use a barrier method of contraception during treatment and for at least 90 days after treatment.

In animal studies, the drug has been shown to be teratogenic. The safety of ganciclovir in human pregnancy has not been established. Prescribing the drug to pregnant women should be avoided unless the potential benefit to the mother outweighs the possible risk to the fetus.

Peri- and postnatal development after exposure to ganciclovir have not been studied, but it cannot be ruled out that ganciclovir may be excreted in milk and cause serious adverse reactions in the nursing infant. Nursing mothers should be instructed to stop breastfeeding while taking Cymeven.

Application for violations of kidney function

Use caution in renal failure. Doses should be adjusted according to QC.

Use in children

Contraindication: children under 12 years of age.

The efficacy and safety of ganciclovir in children, including those with congenital and neonatal CMV infection, have not been established. Because of the potential for late carcinogenicity and reproductive toxicity, extreme caution should be exercised. The benefits of treatment must outweigh the potential risks.

Use in elderly patients

Studies have not been conducted in persons over 65 years of age. Since the renal function is often reduced in the elderly, ganciclovir should be prescribed strictly taking into account renal function.

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