Vayrova (Tablets) Instructions for Use

Marketing Authorization Holder

Sun Pharmaceutical Industries, Ltd. (India)

ATC Code

J05AB11 (Valaciclovir)

Active Substance

Valaciclovir (Rec.INN registered by WHO)

Dosage Form

Vayrova

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

Dosage Form, Packaging, and Composition

Film-coated tablets from light blue to blue, oval, biconvex; on one side of the tablet, engravings “V” and “5” on either side of the score and notches on both sides of the score; a cross-section shows two layers: a blue coating and a white core with blue specks.

Excipients: microcrystalline cellulose (PH101) – 109.425 mg, crospovidone – 7 mg, indigo carmine dye (E132) – 0.3 mg, povidone K30 – 18 mg, povidone K 90D – 2 mg, magnesium stearate – 7 mg.

Film coating composition Opadry 02C50740 blue: hypromellose 5cP (E464) (62%) – 13.02 mg, titanium dioxide (E171) (21%) – 4.41 mg, macrogol/PEG 400 (7%) – 1.47 mg, macrogol/PEG 6000 (6%) – 1.26 mg, indigo carmine dye (E132) 0.42 mg, polysorbate 80 (E433) (2%) – 0.42 mg.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (4) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug

Pharmacotherapeutic Group

Systemic antiviral agents; direct-acting antiviral agents; nucleosides and nucleotides, excluding reverse transcriptase inhibitors

Pharmacological Action

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-affected cells, where, under the influence of the viral enzyme thymidine kinase, it is converted to a monophosphate, then, under the influence of cellular kinases, to 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-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, 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 under the action of 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 after administration of 1 g 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 failure, the T_1/2 of acyclovir is approximately 14 hours.

In late pregnancy, the steady-state daily AUC after administration of 1 g of valaciclovir was approximately 2 times greater than that after administration of 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 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

Administer orally. The specific dosage and duration depend on the indication and patient’s renal function.

For herpes zoster treatment, take 1 g (two 500 mg tablets) three times daily for 7 days. Initiate therapy at the earliest sign or symptom.

For cytomegalovirus prophylaxis post-transplantation, take 2 g (four 500 mg tablets) four times daily. Adjust dose based on renal function. Duration is guided by the period of highest risk.

For patients with renal impairment, adjust the dosage according to creatinine clearance. For herpes zoster: if CrCl 30-49 mL/min, take 1 g every 12 hours; if CrCl 10-29 mL/min, take 1 g every 24 hours; if CrCl <10 mL/min, take 500 mg every 24 hours.

For cytomegalovirus prophylaxis: if CrCl 25-50 mL/min, take 1.5 g four times daily; if CrCl 10-24 mL/min, take 1.5 g three times daily; if CrCl <10 mL/min, take 1.5 g twice daily.

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

Swallow tablets whole with water. Can be taken with or without food.

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, shortness of breath, 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 diseases.

Use in Renal Impairment

Patients with renal failure have an increased risk of developing 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 developing 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 taking valaciclovir at a dose of 1 g, increase the AUC for acyclovir and reduce its renal clearance.

With the simultaneous administration of acyclovir and the inactive metabolite of mycophenolate mofetil (an immunosuppressant used in transplantation), an increase in the AUC of acyclovir and mycophenolate mofetil was observed.

With the simultaneous use of valaciclovir with drugs that impair renal function (including cyclosporine, tacrolimus), deterioration of renal function is possible.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°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.