Valaciclovir-OBL (Tablets) Instructions for Use

Marketing Authorization Holder

FP Obolenskoe, JSC (Russia)

ATC Code

J05AB11 (Valaciclovir)

Active Substance

Valaciclovir (Rec.INN registered by WHO)

Dosage Form

Valaciclovir-OBL

Film-coated tablets, 500 mg: 10, 20, 30, 40, 50, or 60 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, biconvex, oblong in shape, with rounded ends, with a score; on the cross-section, the inner layer is white or almost white.

Excipients: lactose (milk sugar), colloidal silicon dioxide (aerosil), maltodextrin, potato starch, hypromellose (hydroxypropyl methylcellulose), sodium lauryl sulfate, crospovidone (kollidon CL), magnesium stearate.

Shell composition hypromellose (hydroxypropyl methylcellulose), macrogol 6000 (polyethylene glycol 6000), titanium dioxide.

10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (4) – cardboard packs.
10 pcs. – contour cell packs (5) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug

Pharmacotherapeutic Group

Antiviral agent

Pharmacological Action

Antiviral drug. A specific inhibitor of the DNA polymerase of herpes viruses. It blocks the synthesis of viral DNA and virus replication. In the human body, it is converted into acyclovir and L-valine; as a result of phosphorylation, active acyclovir triphosphate is formed from acyclovir, which competitively inhibits viral DNA polymerase.

The first stage of phosphorylation occurs under the influence of a virus-specific enzyme (for Herpes simplex viruses, Varicella zoster, Epstein-Barr virus – viral thymidine kinase, which is found only in virus-infected cells). For cytomegalovirus (CMV), the selectivity of the drug is due to the fact that phosphorylation is partially mediated by the product of the UL97 phosphotransferase gene.

Active in vitro against Herpes simplex viruses types 1 and 2, Varicella zoster virus, Epstein-Barr virus, CMV, and human herpes virus type 6.

Pharmacokinetics

Absorption

Absorption is high, quickly and almost completely converted to acyclovir and L-valine. The bioavailability of acyclovir when taking 1 g of valaciclovir is 54% (3-5 times higher than when taking acyclovir orally).

After using valaciclovir at a dose of 1 g 4 times/day, the AUC is approximately equal to the AUC with intravenous administration of acyclovir at a dose of 5 mg every 8 hours.

C_max after a single dose of 1 g is 15-25 µmol/ml, time to reach C_max is 1.6-2.1 hours; after 3 hours, unmetabolized Valaciclovir is not detected in plasma.

Distribution

Plasma protein binding of valaciclovir is 13-18%, acyclovir is 9-33%.

Acyclovir is widely distributed in body tissues and fluids, including the brain, kidneys, lungs, liver, tear fluid, intestines, muscles, spleen, uterus, vaginal mucosa and secretion, semen, amniotic fluid, cerebrospinal fluid (50% of the plasma concentration), and herpetic vesicle fluid.

The highest concentrations are achieved in the kidneys, liver, and intestines. It penetrates the placenta and into breast milk.

Elimination

T_1/2 of valaciclovir is less than 30 minutes; acyclovir is 2.5-3.3 hours, in end-stage renal failure – 14 hours, in elderly patients (65-83 years) – 3.3-3.7 hours.

It is excreted in the urine (45.6%), mainly in the form of acyclovir and its metabolite 9-carboxymethoxymethylguanine, less than 1% is excreted unchanged and in feces (47.12%) within 96 hours.

Indications

In adults:

• Herpes zoster;
• Diseases of the skin and mucous membranes caused by Herpes simplex virus (including genital herpes);
• Prevention of recurrences of diseases caused by Herpes simplex virus.

In adults and children aged 12 years and older:

• Prevention of cytomegalovirus infection during organ transplantation.

ICD codes

Dosage Regimen

For treatment of herpes zoster, 1 g is prescribed 3 times/day for 7 days; for treatment of infections caused by Herpes simplex, 500 mg 2 times/day.

For recurrences of diseases caused by Herpes simplex virus, treatment begins in the prodromal period or immediately after the first symptoms appear for 5 days; if necessary, at the first stage, the duration of treatment is increased to 10 days.

In chronic renal failure, the dose is reduced: for herpes zoster – 1 g every 12 hours with CrCl 30-49 ml/min; once/day with CrCl 10-29 ml/min; 500 mg once/day with CrCl less than 10 ml/min; for herpes simplex (including genital) herpes – 500 mg every 12 hours with CrCl 30-49 ml/min or once/day with CrCl less than 30 ml/min; in case of hemodialysis, the drug is prescribed after it.

Adverse Reactions

From the digestive system nausea, vomiting, gastralgia, decreased appetite, increased AST activity.

From the CNS dizziness, headache, excessive fatigue;

Other renal failure, microangiopathy, hemolytic anemia, thrombocytopenia (in patients with severe immunodeficiency who received Valaciclovir in high doses (8 g/day) and for a long time).

Contraindications

• Bone marrow transplantation;
• Kidney transplantation;
• Clinically pronounced forms of HIV infection;
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
• Childhood (under 12 years – for the prevention of cytomegalovirus infection during organ transplantation, under 18 years – for other indications);
• Hypersensitivity to the drug.

The drug should be prescribed with caution in hepatic and/or renal failure, during pregnancy and lactation.

Use in Pregnancy and Lactation

There is limited data on the use of valaciclovir during pregnancy. Use is possible only in cases where the potential benefit to the mother outweighs the possible risk to the fetus.

Valaciclovir in unchanged form was not detected in maternal plasma or breast milk. Acyclovir, the main metabolite of valaciclovir, is excreted in breast milk. Considering this, Valaciclovir should be prescribed to the mother with caution during lactation.

Use in Hepatic Impairment

The drug should be prescribed with caution in hepatic insufficiency.

Use in Renal Impairment

The drug should be prescribed with caution in renal insufficiency.

Pediatric Use

Contraindicated: childhood (under 12 years – for the prevention of cytomegalovirus infection during organ transplantation, under 18 years – for other indications).

Special Precautions

In patients with normal immunity, viruses with reduced sensitivity are extremely rare; these viruses are detected relatively more often in individuals with severe immunodeficiency (in recipients of internal organs or bone marrow, patients receiving chemotherapy for malignant neoplasms, HIV-infected).

Reduced sensitivity of viruses to the drug is due to a phenotypic deficiency of thymidine kinase in virus-infected cells, while the virulence of such viruses is close to that of “wild” viruses.

Elderly patients should increase the volume of fluid consumed during treatment.

In the absence of severe renal impairment, no adjustment of the dosage regimen is required.

When treating genital herpes, sexual intercourse should be avoided, because the drug does not protect against transmission of infection.

Taking the drug in high doses for a long time in conditions accompanied by severe immunodeficiency (bone marrow transplantation, clinically pronounced forms of HIV infection, kidney transplantation) led to the development of thrombocytopenic purpura and hemolytic-uremic syndrome, up to a fatal outcome.

Use in pediatrics

Experience with the drug in children is insufficient.

Overdose

Symptoms deposition of the drug in the renal tubules.

Treatment hemodialysis (in acute renal failure and anuria).

Drug Interactions

Cimetidine and blockers of tubular secretion reduce the effect of valaciclovir (reduce the rate, but not the completeness of conversion to acyclovir).

Nephrotoxic drugs increase the risk of nephrotoxicity and CNS disorders.

Storage Conditions

List B. The drug should be stored in a dry, light-protected place, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.