Vayrova, pills 500mg, 10pcs

Composition

1 film-coated tablet contains:

Active ingredient:

valacyclovir hydrochloride 556.275 mg, equivalent to valacyclovir 500 mg

. excipients:

microcrystalline cellulose (PH 101) 109.425 mg,

crospovidone 7 mg,

indigo carmine dye (E 132) 0.3 mg,

povidone (K 30) 18 mg,

povidone (K 90D) 2 mg,

magnesium stearate 7 mg,

purified water q. s. *

Film shell:

Dyestuff Padray 02 S 50740 blue 21 mg, purified water q. s. *Composition of Opadray 02C50740 blue dye: hypromellose 5 cP (E464) 13.02 mg, titanium dioxide (E 171) 5.46 mg, macrogol/PEG 400 1.05 mg, macrogol/PEG 6000 0.63 mg, dye Indigo Carmine (E132) 0.42 mg, polysorbate 80 (e433) 0.42 mg

Pharmacological action

Pharmacodynamics

Valacyclovir: (2S) – [2-[2-Amino-6-oxo-1,6-dihydro-9 N-purine-9-yl)methoxy] ethyl] – 2-amino-3-methylbutanoate hydrochloride is an antiviral drug. Blocks viral DNA synthesis and virus replication. In humans, valacyclovir is converted to acyclovir and valine.

Acyclovir initro has specific activity against herpes simplex viruses types I and II, Varicella zoster virus, cytomegalovirus, Epstein-Barr virus and human herpes virus type VI. Due to phosphorylation, acyclovir is converted to active acyclovir triphosphate, which competitively inhibits viral DNA synthesis. At the first stage of phosphorylation, the activity of a virus-specific enzyme is required. For herpes simplex virus, Varicella zoster virus, and Epstein-Barr virus, this is a viral thymidine kinase found only in cells infected with the virus. In cytomegalovirus infection, acyclovir phosphorylation is mediated by a product of the UL97 phosphotransferase gene.

After oral use, valacyclovir is well absorbed in the gastrointestinal tract( GIT), quickly and almost completely converted to acyclovir and valine. The bioavailability of acyclovir with 1 g of valacyclovir is 54% and does not decrease with simultaneous food intake.

The maximum concentration of acyclovir after a single dose of 250 mg-1 g of valacyclovir is on average 15-25 mmol/l and is reached in 1.6-2.1 hours after use; after 3 hours, valacyclovir is not detected in blood plasma. The binding of valacyclovir to plasma proteins is 13-18%. The elimination half-life of acyclovir after single and repeated use is approximately 3 hours.

Valacyclovir is mainly excreted by the kidneys as acyclovir and its metabolite 9-carboxymethoxymethylguanine. Acyclovir is widely distributed in tissues and body fluids, including the brain, kidneys, lungs, liver, watery moisture, tear fluid, intestines, muscles, spleen, uterus, mucous membrane and vaginal secretions, semen, amniotic fluid, cerebrospinal fluid (CSF) (50% of plasma concentration), herpetic vesicle fluid. The highest concentrations are created in the kidneys, liver, and intestines. Penetrates through the placenta and into breast milk.

Indications

Prparat is used when:

For adults:  

• lip herpes,
• genital herpes (primary and recurrent infection; long-term suppressive therapy for recurrent genital herpes in people with immunodeficiency, including HIV infection; reducing the risk of transmission to a sexual partner),
• herpes zoster.

In adults and children over 12 years of age: prevention of cytomegalovirus infection in organ transplantation.

Use during pregnancy and lactation

There are limited data on the use of valacyclovir in pregnancy. Valacyclovir is only used when the potential benefit to the mother outweighs the potential risk to the fetus.

Registered data on pregnancy outcome in women taking valacyclovir or acyclovir, which is the active metabolite of valacyclovir, did not show an increase in the number of birth defects in their children compared to the general population. Since the register includes a small number of women who took valacyclovir during pregnancy, reliable and definite conclusions about the safety of using valacyclovir during pregnancy cannot be made.

Acyclovir, the main metabolite of valacyclovir, is excreted in breast milk. After taking valacyclovir orally at a dose of 500 mg, the Cmax of acyclovir in breast milk was 0.5-2.3 times (on average,1.4 times) higher than the corresponding concentrations of acyclovir in maternal blood plasma. The ratio of the area under the concentration-time curve (AUC) in blood plasma of acyclovir in breast milk to the area under the concentration-time curve (AUC) of acyclovir in maternal plasma ranged from 1.4 to 2.6 (mean value 2.2). The mean acyclovir concentration in breast milk was 2.24 mcg / ml (9.95 mcg / M). When the mother takes valacyclovir orally at a dose of 500 mg 2 times/day, the child will be exposed to the same effect of acyclovir as when taking it orally at a dose of about 0.61 mg / kg / day. The half-life (T1/2) of acyclovir from breast milk is the same as from blood plasma. Valacyclovir was not detected unchanged in maternal plasma, breast milk, or in the child’s urine.

During breastfeeding, the drug is used only if the intended benefit to the mother exceeds the potential risk to the child. Given this, valacyclovir should be prescribed with caution to the mother during lactation (breastfeeding). However, intravenous (iv) use of acyclovir at a dose of 30 mg / kg / day is used in newborns for the treatment of diseases caused by the herpes simplex virus.

In experimental studies, valacyclovir did not have a teratogenic effect in rats and rabbits. Subcutaneous (subcutaneous) use of acyclovir in conventional teratogenicity tests did not cause teratogenic effects in rats and rabbits. In additional rat studies, fetal developmental disorders were detected with subcutaneous use of the drug in doses that caused an increase in the plasma concentration of acyclovir to 100 mcg / ml and toxic effects in the mother’s body.

When taken orally, valacyclovir did not cause fertility disorders in male and female rats.

Contraindications

• HIV infection with a CD4+ – lymphocyte count of less than 100 / µl,
• Hypersensitivity,
• children’s age (up to 12 years for CMV, up to 18 years for other indications).

With caution. Hepatic / renal insufficiency, elderly age, hypohydration, concomitant use of nephrotoxic drugs, pregnancy, lactation, childhood.

Side effects

Very often ≥1 in 10, often ≥1 in 100, and

From the gastrointestinal tract: often-nausea, infrequently-abdominal pain, vomiting, diarrhea, rarely-increased activity of the “liver enzymes” alanine aminotransferase (ALT), asportate aminotransferase (AST), alkaline phosphatase (ALP), very rarely ‑ hepatitis.

From the blood and lymphatic system: very rarely – leukopenia, thrombocytopenia. Leukopenia is mainly detected in patients with immunodeficiency.

Immune system disorders: very rare-anaphylaxis.

From the nervous system: often-headache, rarely-dizziness, disturbance and confusion, hallucinations, loss of consciousness; very rarely-agitation, tremor, ataxia, dysarthria, psychotic symptoms, convulsions, encephalopathy, coma.

These symptoms are usually reversible and are noted mainly in patients with renal insufficiency or other risk factors. Post-organ transplant patients receiving high-dose valacyclovir to prevent cytomegalovirus infection (8 g per day) experience more neurological reactions than those receiving lower doses.

Respiratory and thoracic disorders: infrequently-shortness of breath.

From the side of the hepatobiliary system: very rarely – a reversible increase in the level of functional liver tests, sometimes regarded as hepatitis.

From the skin and subcutaneous tissues: infrequently-skin rashes, including photosensitization phenomena; rarely-pruritus; very rarely-urticaria, angioedema.

From the side of the kidneys and urinary system: rarely-impaired renal function; very rarely-acute renal failure.

Other: Renal failure, microangiopathy, hemolytic anemia, and thrombocytopenia (sometimes in combination) have been reported in severely immunocompromised patients, especially in patients with advanced HIV infection who have received high doses (8 g per day) of valacyclovir for a long time.

Interaction

Acyclovir is mainly excreted unchanged in the urine by active tubular secretion. Any drugs administered concomitantly with valacyclovir and having this mechanism of elimination may increase the concentration of acyclovir in blood plasma.

Cimetidine and probenecid increase the AUC of acyclovir by reducing its renal clearance, however, there is no need to adjust the dose due to the wide therapeutic index of acyclovir.

Caution should be exercised when prescribing valacyclovir in high doses (4 g / day) for the prevention of cytomegalovirus infection simultaneously with medications that compete with acyclovir for elimination routes, since this may lead to an increase in plasma levels of one or both drugs and their metabolites. When taken concomitantly with mycophenolate mofetil, the concentration of acyclovir and the inactive metabolite mycophenolate mofetil in the blood plasma increases. Caution should also be exercised when concomitantly prescribing valacyclovir in high doses and other drugs that affect renal function (for example, cyclosporine, tacrolimus).

How to take it, course of use and dosage

Inside (regardless of food intake).

For the treatment of herpes zoster, adults are prescribed 1 g 3 times a day. within 7 days.

For the treatment of diseases caused by the Herpes simplex virus, adults are prescribed valacyclovir 500 mg 2 times a day. In case of relapses, treatment should be carried out within 3 or 5 days. In more severe primary cases, treatment should be started as early as possible, and its duration should be increased from 5 to 10 days. In case of relapses of the disease, valacyclovir is considered optimal in the prodromal period or immediately after the first symptoms of the disease appear.

As an alternative for the treatment of lip herpes (lip fever), valacyclovir is effective at a dose of 2 g 2 times for 1 day. The second dose should be taken approximately 12 hours (but not earlier than 6 hours) after the first dose. With this dosage regimen, the duration of treatment should not exceed 1 day, since it does not provide additional clinical benefits. Therapy should be initiated when the earliest symptoms of lip fever appear (i. e. tingling, itching, burning).

To prevent (suppress) relapses of infections caused by the Herpes simplex virus, adults with normal immune parameters are prescribed a dose of 500 mg 1 time/day. Adults with immunodeficiency are recommended to prescribe 500 mg 2 times a day. The duration of treatment is 4-12 months. There are no data on the prevention of infection in other populations of patients.

In patients with renal insufficiency, the dosage regimen is set depending on creatinine clearance (CC) and indications.

INDICATIONSC (ml / min)The dose of valacyclovir for herpes zoster is 15-30 ml / min 1 g 2 times / day. less than 15 ml / min 1 g 1 time/day. Treatment of infections caused by Herpes simplex less than 15 ml / min 500 mg 1 time / day. Treatment of labial herpes 31-49 ml / minpo 1 g 2 times for 1 day 15-30 ml/minpo 500 mg 2 times / day. within 1 day less than 15 ml / min 500 mg once Prevention (suppression) of infections caused by Herpessimplex Less than 15 ml / min in a normal state of immunity: 250 mg 1 time / day in an immunodeficiency: 500 mg 1 time/day To reduce infection with genital herpes less than 15 ml/min 250 mg 1 time/day

Patients undergoing hemodialysis should be prescribed valacyclovir immediately after the end of the hemodialysis session at a dose intended for patients with creatinine clearance less than 15 ml/min. The drug should be used after the end of the hemodialysis session.

For the prevention of cytomegalovirus infection in adults and adolescents over 12 years of age, the recommended dose is 2 g 4 times / day. The drug is prescribed as early as possible after the transplant. The dose should be reduced depending on creatinine clearance (CC). The duration of the course is 90 days, but can be extended in patients with a high risk of developing infections.

Creatinine clearance (ml / min)The dose of valacyclovir is≥752 g 4 times / day. 50 – 25 – 10 – < 10 or hemodialysis 1.5 g 1 time / day.

Frequent monitoring of creatinine clearance is necessary, especially during periods when kidney function changes rapidly (including immediately after transplantation or graft engraftment); the dose of valacyclovir should be adjusted according to creatinine clearance.

Overdose

Symptoms of acute renal failure and neurological symptoms, including confusion, hallucinations, agitation, loss of consciousness and coma in patients with valacyclovir overdose, nausea and vomiting. To prevent overdose, you need to be careful when using the drug. Many of the reported cases of repeated overdose in patients with impaired renal function and in elderly patients were caused by insufficient dose reduction.

Treatmentspatients should be carefully monitored for timely diagnosis of toxic symptoms. Hemodialysis significantly accelerates the elimination of acyclovir from the blood and can be considered the optimal treatment method in the case of symptomatic overdose.

Special instructions

Hydration. Elderly patients, people with dehydration during treatment with valacyclovir should increase the volume of fluid consumed. In the absence of severe renal impairment, no dosage adjustment is required.

Use in patients with impaired renal function and in elderly patients. Valacyclovir is excreted through the kidneys, and therefore elderly patients with a possible decrease in renal function should reduce the dose of the drug. In patients with a history of kidney pathology, the risk of developing nephrological complications increases, and in order to detect them in a timely manner, such patients should be carefully monitored.

Reduced transmission of genital herpes virus. Suppressive therapy with valacyclovir reduces the risk of transmission of genital herpes, but does not cure herpes infection and does not completely eliminate the risk of transmission of the virus, it is recommended to avoid sexual contact.

Breast-feeding period. It is recommended that valacyclovir be administered with caution to women who are breast-feeding.

Influence on the ability to drive motor vehicles and other mechanisms. There are no special warnings.

If side effects from the central nervous system occur (including agitation, hallucinations, confusion, delirium, convulsions and encephalopathy), the drug is discontinued.

Form of production

Film-coated tablets

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Valacyclovir

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Children over 12 years of age, Children as prescribed by a doctor, Adults as prescribed by a doctor

Indications

Cold, Cytomegalovirus Infection, Herpes, Chickenpox