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

Antiviral, L-valyl ester of ganciclovir. Is a prodrug of ganciclovir. After oral administration, it is rapidly transformed into ganciclovir with the participation of esterases of the intestine and liver.

Ganciclovir is a synthetic analogue of guanine. Inside the cage ganciclovir is subsequently metabolized to the form of monophosphate with the participation of cellular deoxyguanosine kinase, then into the active ganciclovir triphosphate. Acting as a substrate and embedded in DNA, ganciclovir triphosphate competitively inhibits the synthesis of viral DNA. This leads to suppression of DNA synthesis by inhibiting the elongation of the DNA chain. Ganciclovir suppresses viral DNA polymerase more actively than cellular polymerase.

Valganciclovir is sensitive to human cytomegalovirus, Herpes simplex types 1 and 2, Varicella zoster, Epstein-Barr virus and hepatitis B virus.

Pharmacokinetics:

After oral administration, it is rapidly absorbed from the gastrointestinal tract, in the intestinal wall and in the liver, into ganciclovir. The absolute bioavailability of ganciclovir after its conversion from valganciclovir is approximately 60%. The binding of ganciclovir to plasma proteins is 1-2%.

It is excreted mainly by the kidneys.

After taking valganciclovir, the final half-life Ganciclovir is about 4.2 h.

Indications:

Treatment of cytomegalovirus retinitis in AIDS.

Prevention of cytomegalovirus infection after organ transplantation in patients at risk.

ICD-10

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

Contraindications:

Children up to 12 years; increased sensitivity to valganciclovir, ganciclovir.

Carefully:

Use with caution in elderly patients (safety and efficacy of the drug are not established).

Pregnancy and lactation:

FDA recommendation category C.Adequate and well-controlled studies on 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 used in animals has a carcinogenic and teratogenic effect.

Penetrates into breast milk (usually in low concentrations). Violations are not registered. In a typical clinical pharmacological article, it is recommended to stop breastfeeding, in all other sources (USP, the federal government) - to compare the risk and benefit, especially when using inhalation, the concentrations often do not reach the detection limit.

Dosing and Administration:

Inside to 450 mg 1-2 times a day in accordance with the scheme of treatment.

Patients with impaired renal function, patients on hemodialysis, as well as with oppression of bone marrow hematopoiesis require a correction of the dosing regimen.

Side effects:

Most often: diarrhea (38%), fever (26%), nausea (25%), neutropenia (24%) and anemia (22%). Most of them were mild or moderate.

From the digestive system: ≥ 5% - diarrhea, nausea, vomiting, abdominal pain, constipation, pain in the upper abdomen, indigestion, bloating, ascites, impaired liver function.

On the part of the body as a whole: ≥ 5% - fever, fatigue, swelling of the lower extremities, pain, swelling, peripheral edema, weakness.

From the side of the blood and lymphatic system: ≥ 5% - neutropenia, anemia, thrombocytopenia, leukopenia; <5% - pancytopenia, suppression of bone marrow function, aplastic anemia; potentially life-threatening hemorrhages associated with the development of thrombocytopenia.

Infectious complications: ≥ 5% - candidiasis of the oral mucosa, pharyngitis / nasopharyngitis, sinusitis, upper respiratory tract infections, influenza, pneumonia, bronchitis, pneumocystis pneumonia, urinary tract infections.

From the nervous system: ≥ 5% - headache, insomnia, peripheral neuropathy, paresthesia, tremor, dizziness (except vertigo), depression; <5% - convulsions, psychotic disorders, hallucinations, confusion, agitation.

From the side of the skin and subcutaneous fat: ≥ 5% - dermatitis, night sweats, itching, acne.

From the respiratory system: ≥ 5% - cough, shortness of breath, productive cough, discharge from the nose, pleural effusion.

From the sense organs: ≥ 5% - retinal detachment, fuzzy vision.

From the musculoskeletal system: ≥ 5% - back pain, arthralgia, muscle cramps, pain in the limbs.

From the urinary system: ≥ 5% - renal failure, dysuria; <5% decrease in creatinine clearance.

FROMabout the side of the immune system: ≥ 5% - transplant rejection reaction.

From the side of metabolism: ≥ 5% - anorexia, cachexia, decreased appetite, dehydration, weight loss.

From the cardiovascular system: ≥ 5% - arterial hypotension, arterial hypertension.

From the laboratory indicators: ≥ 5 % - hyperkalemia, hypokalemia, hypomagnesemia, hyperglycemia, hypophosphatemia, hypocalcemia, hypercreatininaemia.

Postoperative complications: ≥ 5% - postoperative complications, pain in the postoperative period, infection of the postoperative wound, increase in the frequency of the need for drainage, poor healing of the postoperative wound

On the part of the body as a whole: <5% - hypersensitivity reactions to valganciclovir.

Overdose:

Headache, convulsions, drowsiness, coma, acute renal failure.

Treatment is symptomatic.

Interaction:

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

Zidovudine - the emergence 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.

Drugs that depress hemopoiesis, radiation therapy - strengthening of myelodepression.

Special instructions:

Due to the similar chemical structure of valganciclovir and acyclovir, valaciclovir, cross-sensitivity reactions to these drugs are possible.

In experimental animal studies, mutagenic, teratogenic, aspermatogenic and carcinogenic effects of ganciclovir have been identified. Valganciclovir should be considered a potential teratogen and a carcinogen for a person whose use can cause congenital malformations and cancer.In addition, it is likely that valganciclovir can temporarily or irreversibly suppress spermatogenesis.

Treatment should not be started if the absolute number of neutrophils is less than 500 cells / μl or the platelet count is less than 25,000 cells / μl, and if hemoglobin is below 80 g / l.

During the treatment it is recommended to regularly monitor the developed formula of blood and platelets. Patients with severe leukopenia, neutropenia, anemia and / or thrombocytopenia are recommended to prescribe hematopoietic growth factors and / or interrupt the use of valganciclovir.

Avoid simultaneous use of valganciclovir and imipenem / cilastatin in cases where the potential benefits of treatment do not exceed the possible risk.

Since both zidovudine, and ganciclovir may cause neutropenia and anemia, some patients may be intolerant while taking valganciclovir and zidovudine in full doses.

In connection with the possible increase in plasma concentrations of didanosine in the presence of ganciclovir, the patients should be carefully monitored for symptoms of toxic effects of didanosine.

In the treatment of valganciclovir and / or ganciclovir, seizures, sedation, dizziness, ataxia and / or confusion may occur, which can adversely affect activities requiring increased concentration of attention, including driving and working with machines and mechanisms.

Instructions

Valganciclovir (Valgancyclovirum)