Valavir (Tablets) Instructions for Use

Marketing Authorization Holder

Farmak, JSC (Ukraine)

ATC Code

J05AB11 (Valaciclovir)

Active Substance

Valaciclovir (Rec.INN registered by WHO)

Dosage Form

Valavir

Film-coated tablets, 500 mg: 10 or 42 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blisters (1) – cardboard packs.
6 pcs. – blisters (7) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug

Pharmacotherapeutic Group

Antiviral agent

Pharmacological Action

Valaciclovir is an antiviral agent from the group of nucleoside analogues. Valaciclovir is the L-valine ester of acyclovir, thus being a prodrug.

After absorption into the bloodstream, Valaciclovir is almost completely converted to acyclovir under the influence of the hepatic enzyme valaciclovir hydrolase. The acyclovir formed from valaciclovir, in turn, penetrates into virus-affected cells, where, under the influence of the viral enzyme thymidine kinase, it is converted into a monophosphate, then, under the influence of cellular kinases, into a diphosphate and active triphosphate. Acyclovir triphosphate inhibits DNA polymerase and thus disrupts viral DNA replication.

Furthermore, disruption of viral DNA replication can result from the incorporation of acyclovir into its structure. Thus, the high selectivity of valaciclovir for virus-affected tissues is explained by the fact that the first stage of the phosphorylation reaction chain is mediated by an enzyme produced by the virus itself.

It is active against Herpes simplex viruses types 1 and 2, Varicella zoster, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6.

Pharmacokinetics

After oral administration, Valaciclovir is well absorbed from the gastrointestinal tract, rapidly and almost completely converted to acyclovir and L-valine by the enzyme valaciclovir hydrolase.

After a single dose of 0.25-2 g of valaciclovir, the C_max of acyclovir in healthy volunteers with normal renal function averages 10-37 µmol (2.2-8.3 µg/ml) and is reached within 1-2 hours.

The bioavailability of acyclovir from a 1 g dose of valaciclovir is 54% and does not depend on food intake.

The C_max of valaciclovir in plasma is only 4% of the acyclovir level and is reached on average 30-100 minutes after drug administration; after 3 hours, the C_max level remains the same or decreases.

The binding of valaciclovir to plasma proteins is very low – 15%.

In patients with normal renal function, the T_1/2 of acyclovir is about 3 hours. Valaciclovir is excreted in the urine, mainly as acyclovir (more than 80% of the dose) and its metabolite 9-carboxymethoxymethylguanine; less than 1% of the drug is excreted unchanged.

In patients with end-stage renal disease, the T_1/2 of acyclovir is approximately 14 hours.

In late pregnancy, the steady-state daily AUC after a 1 g dose of valaciclovir was approximately 2 times greater than that after a 1.2 g/day dose of acyclovir.

In organ transplant recipients receiving Valaciclovir at a dose of 2 g 4 times/day, the C_max of acyclovir is equal to or exceeds that in healthy volunteers receiving the same dose of valaciclovir, and their daily AUC values are significantly higher.

Indications

Treatment and prevention of infectious diseases caused by Herpes zoster.

Prevention of cytomegalovirus infection developing during organ transplantation.

ICD codes

Dosage Regimen

Take tablets orally with a full glass of water.

For herpes zoster treatment, take 1 g (1000 mg) three times daily for 7 days.

For cytomegalovirus infection prevention post-transplantation, take 2 g (2000 mg) four times daily.

Initiate therapy at the earliest sign or symptom.

Adjust dosage for all patients with renal impairment based on creatinine clearance.

For creatinine clearance 30-49 mL/min, administer 1 g twice daily for herpes zoster.

For creatinine clearance 10-29 mL/min, administer 1 g once daily for herpes zoster.

For creatinine clearance less than 10 mL/min, administer 500 mg once daily for herpes zoster.

For cytomegalovirus prophylaxis, adjust dose to 1.5 g twice daily if clearance is 50-75 mL/min.

For cytomegalovirus prophylaxis, adjust dose to 1.5 g once daily if clearance is 25-50 mL/min.

For cytomegalovirus prophylaxis, adjust dose to 1 g once daily if clearance is 10-25 mL/min.

Do not use for cytomegalovirus prophylaxis if creatinine clearance is less than 10 mL/min.

In elderly patients, ensure adequate hydration during treatment.

Complete the full prescribed course of therapy unless otherwise directed.

Adverse Reactions

From the digestive system nausea, discomfort, abdominal pain, vomiting, diarrhea, anorexia; rarely – transient increase in liver function tests.

From the CNS headache, fatigue, dizziness, confusion, hallucinations; rarely – consciousness disorders; in some cases – coma (usually in patients with impaired renal function or other predisposing factors).

Allergic reactions rarely – rash, urticaria, itching, angioedema, anaphylaxis.

Other rarely – thrombocytopenia, dyspnea, renal function disorders, photosensitivity.

Contraindications

Hypersensitivity to valaciclovir, acyclovir.

Use in Pregnancy and Lactation

Adequate and strictly controlled studies on the safety of valaciclovir use during pregnancy and lactation have not been conducted. Use in this category of patients is possible in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus or breastfed infant.

It is known that acyclovir, a metabolite of valaciclovir, is excreted in breast milk at concentrations 0.6-4.1 times higher than its concentrations in plasma. The T_1/2 of acyclovir from breast milk is 2.8 hours, which is comparable to the T_1/2 from blood plasma.

Use in Hepatic Impairment

Use with caution in patients with liver diseases.

Use in Renal Impairment

Patients with renal failure have an increased risk of neurological complications when taking valaciclovir.

Pediatric Use

There is no clinical experience of use in children.

Geriatric Use

Elderly patients should increase their fluid intake during treatment.

Special Precautions

Elderly patients should increase their fluid intake during treatment.

Patients with renal failure have an increased risk of neurological complications when taking valaciclovir.

Use with caution in patients with liver diseases.

There is no clinical experience of use in children.

Drug Interactions

Acyclovir in its unchanged form enters the urine as a result of active tubular secretion. Any drugs that are administered concurrently and compete for this elimination mechanism can cause an increase in the plasma concentration of valaciclovir. Cimetidine and drugs that block tubular secretion, when administered after a 1 g dose of valaciclovir, increase the AUC for acyclovir and reduce its renal clearance.

When acyclovir and the inactive metabolite of mycophenolate mofetil (an immunosuppressant used in transplantation) were taken simultaneously, an increase in the AUC of both acyclovir and mycophenolate mofetil was observed.

When valaciclovir is used concomitantly with drugs that impair renal function (including cyclosporine, tacrolimus), deterioration of renal function is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.