Valacitek (Tablets) Instructions for Use

Marketing Authorization Holder

Scan Biotech LLC (India)

Manufactured By

Vivimed Labs, Ltd. (India)

Labeled By

VIVIMED LABS, Ltd. (India)

Or

ROZLEKS PHARM, LLC (Russia)

ATC Code

J05AB11 (Valaciclovir)

Active Substance

Valaciclovir (Rec.INN registered by WHO)

Dosage Forms

	Valacitek	Film-coated tablets, 500 mg: 8, 10, 16, 40, 42 or 48 pcs.
		Film-coated tablets, 1000 mg: 7, 8, 10, 28 or 32 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets blue, oval, biconvex; the core is white on the cross-section.

Excipients : microcrystalline cellulose – 115.1 mg, povidone (K-30) – 24.5 mg, magnesium stearate – 4.2 mg.

Shell compositionOpadry blue (06B30583) – 21 mg (hypromellose (3cps) – 7.35 mg, hypromellose – 6.3 mg, titanium dioxide – 2.5368 mg, macrogol 400 – 2.1 mg, indigo carmine dye (FD&C blue #2) – 1.6632 mg, hypromellose (50cps) – 1.05 mg.

6 pcs. – blisters (7) – carton packs.
8 pcs. – blisters (1) – carton packs.
8 pcs. – blisters (2) – carton packs.
8 pcs. – blisters (5) – carton packs.
8 pcs. – blisters (6) – carton packs.
10 pcs. – blisters (1) – carton packs.

Film-coated tablets blue, oval, biconvex, with a score on one side; the core is white on the cross-section.

Excipients : microcrystalline cellulose – 230.2 mg, povidone (K-30) – 49 mg, magnesium stearate – 8.4 mg.

Shell compositionOpadry blue (06B30583) – 42 mg (hypromellose (3cps) – 14.7 mg, hypromellose – 12.6 mg, titanium dioxide – 5.0736 mg, macrogol 400 – 4.2 mg, indigo carmine dye (FD&C blue #2) – 3.3264 mg, hypromellose (50cps) – 2.1 mg.

7 pcs. – blisters (1) – carton packs.
7 pcs. – blisters (4) – carton packs.
8 pcs. – blisters (1) – carton packs.
8 pcs. – blisters (4) – carton packs.
10 pcs. – blisters (1) – carton packs.

Clinical-Pharmacological Group

Antiviral drug

Pharmacotherapeutic Group

Antiviral agent

Pharmacological Action

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

After absorption into the blood, 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-infected 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 the active triphosphate. Acyclovir triphosphate inhibits DNA polymerase and thus disrupts viral DNA replication. Furthermore, disruption of viral DNA replication may result from the incorporation of acyclovir into its structure. Thus, the high selectivity of valaciclovir for virus-infected 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 achieved 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 taking 1 g of valaciclovir was approximately 2 times greater than that after taking acyclovir at a dose of 1.2 g/day.

In organ transplant recipients receiving valaciclovir at a dose of 2 g 4 times/day, the C_max of acyclovir was equal to or exceeded that in healthy volunteers receiving the same dose of valaciclovir, and their daily AUC values were 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 water, with or without food.

For treatment of herpes zoster, take 1000 mg three times daily for 7 days. Initiate therapy at the earliest sign or symptom.

For prevention of cytomegalovirus infection post-transplantation, take 2000 mg four times daily. Adjust dose based on renal function. Duration is determined by the duration of immunosuppression, typically up to 90-100 days.

For patients with renal impairment, adjust dosage according to creatinine clearance. For herpes zoster with CrCl 30-49 mL/min, take 1000 mg twice daily. With CrCl 10-29 mL/min, take 1000 mg once daily. With CrCl less than 10 mL/min, take 500 mg once daily.

For CMV prophylaxis with CrCl 25-50 mL/min, take 1500 mg twice daily. With CrCl 10-24 mL/min, take 1500 mg once daily. With CrCl less than 10 mL/min, take 500 mg once daily.

In elderly patients, ensure adequate hydration during treatment. Assess renal function before initiation and adjust dose accordingly.

Do not exceed the recommended dosage or duration of therapy. Complete the full prescribed course 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 – impaired consciousness; 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 impairment, 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, which is 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 disease.

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 disease.

There is no clinical experience of use in children.

Drug Interactions

Acyclovir enters the urine unchanged 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 acyclovir and mycophenolate mofetil was observed.

When valaciclovir is used concomitantly with drugs that impair renal function (including cyclosporine, tacrolimus), renal function may worsen.

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.