Valacyclovir

When ATH:
J05AB11

Valaciclovir is the hydrochloride salt, L-valyl ester of acyclovir. Valacyclovir hydrochloride - white or almost white powder; maximum solubility in water (at 25 °C) - 174 mg / ml; molecular weight 360,80.

Pharmacological action.
Antiviral, antiherpetic.

Application.

Shingles; infections of the skin and mucous membranes, HSV (incl. genital herpes); relapse prevention, herpes simplex virus.

Hypersensitivity (incl. acyclovir), bone marrow transplantation, kidney transplantation (cm. Precautions).

Renal dysfunction, symptomatic forms of HIV infection, Children up to age 12 years (Safety and efficacy have not been determined).

Pregnancy. Maybe, if the effect of therapy outweighs the potential risk to the fetus (adequate and well-controlled studies of the safety of use in pregnant women were not conducted).

Data on the outcome of pregnancy in women, taking acyclovir for systemic effects in the I trimester of pregnancy (Acyclovir is an active metabolite of valaciclovir), showed no increase in the number of birth defects compared to the general population. As the observation was included a small number of women, reliable and definitive conclusions about the safety of valaciclovir in pregnancy can not be done.

Category actions result in FDA - B. (The study of reproduction in animals revealed no risk of adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not done.)

Lactation. Acyclovir, the major metabolite of valaciclovir, excreted in breast milk. Following the appointment of an oral dose of valacyclovir 500 mg C_max acyclovir in breast milk in 0,5-2,3 times (on average 1,4 times) higher than the corresponding concentrations in maternal blood. Отношение AUC ацикловира, present in breast milk, to the AUC of acyclovir in maternal plasma was 1,4-2,6 (average 2,2). The average value of the concentration of acyclovir in breast milk - 2,24 ug / ml. When you assign a nursing mother at a dose of valaciclovir 500 mg 2 times a day a child will undergo the same effects of acyclovir, it when receiving an oral dose of about 0,61 mg / kg / day. Valacyclovir in unchanged form is not determined in the blood and breast milk of the mother or the child's urine. Valaciclovir should be used with caution lactating women, only if necessary.

In the table 1 presents side effects, often observed in the treatment with valacyclovir (1 g 3 once a day) in immunocompetent patients with herpes zoster during the randomized, double-blind clinical trials.

Side effects, observed in clinical trials in patients with herpes zoster

In the table 2 presents side effects, observed in the treatment with valacyclovir in patients with genital herpes during the clinical trials.

Side effects, observed in clinical trials in patients with genital herpes

If suppressive (preventive, preventive) therapy to prevent recurrences of genital herpes in HIV-infected patients, taking valacyclovir at a dose 500 mg 2 once a day (n=194) placebo (n=99), frequently observed side effects, headache (13 and 8% respectively), fatigue (8/5%), rash (8/1%). Patients, taking valacyclovir, There were also laboratory abnormalities (vs placebo): increased levels of alkaline phosphatase (4/2%), GOLD (14/10%), IS (16/11%), reduction in the number of neutrophils (18/10%) and platelets (3/0%).

Cooperation.

Clinically significant interactions in patients with normal renal function is not installed. Cimetidine and probenecid (alone or together) after receiving a single dose of valaciclovir 1000 mg C increase_makh and AUC and reduce the renal clearance of acyclovir. The pharmacokinetics of valaciclovir is not changed while receiving with digoxin, aluminum / magnesium-containing antacids, thiazide diuretics.

Nephrotoxic drugs increase the risk of renal failure and disorders of the nervous system.

Overdose.

Symptoms: sedimentation of acyclovir in renal tubules.

Treatment: hemodialysis (in acute renal failure and anuria).

Dosing and Administration.

Inside (regardless of the meal). The batch is individually, depending on the evidence. Therapy is recommended to start as early as possible, says the greatest efficiency, if treatment was started within 48 h from the first onset of signs or symptoms of the disease (rashes, pain or burning sensation). When shingles - by 1000 mg 3 twice a day for 7 days.

When herpes simplex, including recurrent genital herpes, - By 500 mg 2 twice a day during 5-10 days.

In patients with renal insufficiency dose reduced: with herpes zoster - for 1000 mg every 12 Cl creatinine hours at 30-49 ml / min or 1 times a day with creatinine Cl 10-29 ml / min and 500 mg 1 once a day at the Cl creatinine less than 10 ml / min; by simply (including genital) herpes - on 500 mg every 12 Cl creatinine hours at 30-49 ml / min or 1 once a day at the Cl creatinine less than 30 ml / min; in the case of hemodialysis drug prescribed after.

Precautions.

With caution is prescribed for any conditions, accompanied immunodeficient, especially in HIV-infected patients. During clinical trials when taking high doses of valaciclovir (8 g / day) for a long time and recorded thrombocytopenic purpura / hemolytic uremic syndrome, or, in rare cases with fatal outcome, in patients with symptomatic forms of HIV infection, after transplantation of bone marrow or kidney (cm. "Contra" and "Restrictions on the use"). Not established the efficacy and safety of valacyclovir in immunocompromised patients (except for the suppressive therapy of genital herpes in HIV-infected patients), for the suppressive therapy of recurrent genital herpes in patients with symptomatic forms of HIV (CD4 cell count <100 cells / mm³), for the treatment of genital herpes in HIV-infected patients, for the treatment of generalized herpes zoster, to reduce the possibility of infection with genital herpes healthy partner.

Use caution when kidney function (lengthened T_1/2 acyclovir), necessary correction mode, depending on the degree of violation of their functions (cm. "Dosage and administration"). Patients with kidney disease, receiving high doses of valaciclovir, there have been cases of acute renal failure and disorders of the central nervous system.

Older patients during treatment is recommended to increase fluid intake.

During the treatment of genital herpes should avoid sexual contact (the drug does not protect against transmission of infection).