Ganciclovir - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Antiviral drugs (excluding HIV)

Included in the formulation

Ganciclovir

lyophilizate d / infusion

BELMEDPREPARATY, RUP Republic of Belarus

ZIRGAN®

gel d / eye

LABORATOUR TEA France

Tzymoven

lyophilizate in / in d / infusion

Hoffmann-La Roche Ltd. Switzerland

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

ONLS

АТХ:

J.05.A.B.06 Ganciclovir

S.01.A.D.09 Ganciclovir

Pharmacodynamics:Capture and phosphorylation of ganciclovir with viral thymidine kinase (affinity for the viral enzyme is 200 times higher than the affinity for thymidine kinase of the host cells) - formation of ganciclovir monophosphate, selective accumulation in virus-infected cells (concentration 10 times higher than that of uninfected cells). Conversion of the latter (under the influence of cellular phosphorylases) to ganciclovortriophosphate: competitive inhibition of viral DNA polymerase (and to an insignificant degree of DNA polymerase of host cells); incorporation into the viral DNA - replication stop (no hydroxy group at the 3'-position of the ribose ring), binding defective DNA viral DNA polymerase and its inhibition irreversible.

Pharmacokinetics:Bioavailability - 3-5% (increase with simultaneous intake with food). V_d - 1,1 ± 0,3 l / kg. The concentration in the central nervous system is 20-70% plasma.The connection with plasma proteins is 1-2%. Biotransformation is insignificant or absent. Half-life with intravenous administration is 2.5-3.6 hours, with creatinine clearance of 20-50 ml / min - 9-30 hours. Half-life with ingestion 3.1-5.5 hours, with creatinine clearance of 10-50 ml / min - 15,7-18,2 h, the half-life within the cell in the form of ganciclovurtrisphosphate 7-20 hours. Clearance - 4.6 ± 1.8 ml / min (decreases with chronic renal failure). Eliminated unchanged by the kidneys (90-100%). Removed during hemodialysis (50%).

Indications:Infections caused by Herpesviridae: Herpes simplex 1-st and 2-nd types, Varicella zoster, Epstein-Barr and cytomegalovirus (most active in relation to the latter).

Treatment and prevention of cytomegalovirus infection (retinitis, colitis, esophagitis, pneumonia, polyradiculopathy and others) in immunocompromised patients with AIDS, immunosuppressive therapy.

ICD-10

I.B25-B34.B25 Cytomegalovirus

I.B20-B24.B20.2 The disease caused by HIV, with manifestations of cytomegalovirus disease

Contraindications:Hypersensitivity to the drug; congenital or neonatal cytomegalovirus infection; pregnancy and the period of breastfeeding; severe oppression of bone marrow hematopoiesis (neutropenia less than 0.5 × 109 / L,thrombocytopenia less than 25 × 109 / l); children under 12 years of age (safety and efficacy not studied).

Carefully:In cancer patients who have recently undergone chemotherapy or radiation therapy. In other patients with impaired bone marrow function or signs of myelosuppression. In patients with impaired renal function, the dose is reduced, guided by the clearance of creatinine. With an increase in serum creatinine and urea nitrogen levels, to prevent an overdose, lower the dose of the drug and increase the interval between administration.

Pregnancy and lactation:FDA category C recommendations. Qualitative and well-controlled studies in humans have not been conducted. Women of childbearing age and men during the admission and within 90 days after completion of the course of treatment should use barrier methods of contraception. When administered to animals, the drug has a carcinogenic and teratogenic effects. Penetrates into breast milk (usually - in low concentrations). The decision to cancel the drug or stop breastfeeding should be taken in consideration of the positive potential effect for the nursing mother.

Dosing and Administration:Treatment and prevention of cytomegalovirus infection in immunocompromised patients with AIDS, immunosuppressive therapy (including after organ transplantation operations), chemotherapy of malignant neoplasms: intravenously at 5 mg / kg at a constant rate for 1 hour every 12 hours (daily dose - 10 mg / kg per day). The course of treatment is 14-21 days. Long-term maintenance treatment - 6 mg / kg per day for 5 days or 5 mg / kg per day daily (performed also in patients at risk of relapse). Preventive treatment - 1 g 3 times a day.

With cytomegalovirus retinitis, the course of treatment is carried out according to the following scheme (regardless of the purpose of maintenance therapy). The drug is injected into the vitreous humor at a dose of 200 μg 2 times a week for 3 weeks. In chronic renal failure and creatinine clearance of 125-225 μmol / l, the drug is administered at 2.5 mg / kg after 12 hours; with creatinine clearance of about 225-398 μmol / L - 2.5 mg / kg every 24 hours, with a clearance of more than 398 μmol / l - at 1.25 mg / kg after 24 hours. Introduction to the vitreous humor at a dose of 200 mcg is performed once a week. When stabilized against the background of induction therapy, a maintenance dose is prescribed - inside (at meal time) 1 g 3 times a day or 0.5 g 6 times a day (during the waking period).

Side effects:Neutropenia and granulocytopenia (sore throat, hyperthermia, chills), thrombocytopenia (bleeding, hemorrhage), less often anemia (excessive fatigue or weakness), pancytopenia, splenomegaly.

Arrhythmias, lability of arterial pressure, deep vein thrombophlebitis, vasodilation.

Obsessive, nightmarish, ataxia, coma, confusion, insomnia, neuropathy, thinking disorder, dizziness, headache, migraine, anxiety, mood lability, nervousness, paresthesia, hyperkinesia, psychosis, epileptic seizures.

Visual impairment, when introduced into the vitreous body - bacterial endophthalmitis, minor conjunctival scarring, foreign body sensation in the eye, retinal detachment in patients with AIDS and cytomegalovirus retinitis, injection of scleral vessels or subconjunctival hemorrhage, pain in the eyes and ears, amblyopia, vision loss, conjunctivitis, perversion of taste, deterioration of hearing.

Eructation, esophagitis, nausea, vomiting, dry mouth, decreased appetite, aphthous stomatitis, diarrhea, flatulence, abdominal pain, fecal incontinence, hepatitis (jaundice, increased activity of transaminases and alkaline phosphatase), gastrointestinal bleeding, abdominal pain, pancreatitis.

Myasthenia gravis, myalgia, arthralgia, ossalgia, cramps in the calf muscles, back pain, tremor.

Hematuria, swelling, increased urination, urinary tract infection, impaired renal function (hypercreatininaemia, increased urea concentration), decreased libido; when used in high doses - irreversible suppression of spermatogenesis in men and fertility in women.

Itching, maculopapular rash, hives, chills, eosinophilia, hyperthermia.

Soreness along the vein, phlebitis.

Other: infection, phlegmon, acne, chest pain, hypoglycemia, alopecia, weight loss, dyspnea, carcinogenicity.

Overdose:Symptoms: headache, convulsions, drowsiness, coma, acute renal failure. The goals of therapy for overdose - the maintenance of vital functions, the rapid appointment of symptomatic therapy and hemodialysis.

Interaction:Didanosine - increased risk of toxicity (the interval between doses should be more than 2 hours).

Zidovudine - the appearance of fatigue.

Imipenem, cilastatin - the risk of generalized seizures.

Interferon alfa - the risk of developing kidney failure.

Mycophenolic acid - mutual suppression of elimination (especially in the background of chronic renal failure).

Nephrotoxic drugs increase the likelihood of developing kidney failure.

Means, depressing hematopoiesis, radiation therapy - strengthening of myelodepression.

Special instructions:In severe violations of kidney function, the dose of the drug should be reduced. The dose is selected individually. They focus on urea and blood creatinine, daily diuresis and creatinine clearance.

Monitoring: nitrogen, urea, blood creatinine (before and during treatment); indicators of peripheral blood and leukocyte formula, the number of platelets; functional tests of the liver, ophthalmological examination in dynamics.

Patients at the time of treatment need to take a large amount of fluid in order to speed up the removal of the drug.

It is possible to increase the toxicity with rapid jet administration of the drug. It is necessary to administer a single dose of drip, for an hour. Avoid contact with skin and mucous membranes.

Instructions

Ganciclovir (Gancyclovirum)