VAYROVA PILLS 500MG

Composition

1 tablet, film coated, contains:
active ingredient: Valaciclovir hydrochloride 556.275 mg, equivalent to valacyclovir 500 mg.
excipients: microcrystalline cellulose (PH 101) 109.425 mg, crospovidone 7 mg, dye indigo carmine (E132) 0.3 mg, povidone (K 30) 18 mg, povidone (K 90D) 2 mg, Magnesium stearate 7 mg, purified water qs *
Film casing: dye Hip 02S50740 blue 21 mg, purified water q.s. *
The composition of the dye Opadray 02C50740 blue: hypromellose 5 cP (E464) 13.02 mg, titanium dioxide (E171) 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

Mechanism of action

Pharmacodynamics
Valacyclovir: (2S) - [2- [2-Amino-6-oxo-1,6-dihydro-9H-purin-9-yl) methoxy] ethyl] -2-amino-3-methylbutanoate hydrochloride is an antiviral drug. Blocks viral DNA synthesis and virus replication. In humans, valaciclovir is converted to Acyclovir and valine. Initro acyclovir has specific activity against herpes simplex viruses type 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. In the first stage of phosphorylation, the activity of a virus-specific enzyme is necessary.For herpes simplex virus, Varicella zoster virus and Epstein-Barr virus, it is viral thymidine kinase, which is only found in cells infected with the virus. In cytomegalovirus infection, acyclovir phosphorylation is mediated by the UL97 phosphotransferase gene product.

Pharmacokinetics
After oral administration, valaciclovir is well absorbed in the gastrointestinal tract (GIT), quickly and almost completely converted into acyclovir and valine. The bioavailability of acyclovir when taking 1 g of valaciclovir is 54% and does not decrease with simultaneous ingestion of food. The maximum concentration of acyclovir after a single dose of 250 mg - 1 g of valaciclovir averages 15-25 mcmol / l and is reached 1.6-2.1 hours after administration; after 3 hours, valacyclovir in plasma is not detected. The binding of valacyclovir to plasma proteins is 13-18%. The half-life of acyclovir after single and repeated use is approximately 3 hours. Valacyclovir is excreted by the kidneys, mainly in the form of acyclovir and its metabolite 9-carboxymethoxymethylguanine. Acyclovir is widely distributed in tissues and body fluids, including the brain, kidneys, lungs, liver, aqueous humor, tear fluid, intestines, muscles, spleen, uterus, mucous membrane and vaginal secretions, semen, amniotic fluid, cerebrospinal fluid (CSF) ( 50% of plasma concentration), fluid herpetic vesicles. The highest concentrations are found in the kidneys, liver and intestines.Penetrates through the placenta and into breast milk.

Indications and usage

Prparat applied to:

In adults:

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

In adults and children over 12 years old: prevention of cytomegalovirus infection with organ transplantation.

Contraindications

• HIV infection with a CD4 + lymphocyte content of less than 100 / μl,
• Hypersensitivity
• children's age (up to 12 years with CMV, up to 18 years - according to other indications).

Carefully. Hepatic / renal failure, advanced age, hypohydration, simultaneous administration of nephrotoxic drugs, pregnancy, lactation period, children's age.

Adverse reactions

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

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

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

On the part of the immune system: very rarely - anaphylaxis.

On the part of 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 reversible in most cases and are noted mainly in patients with renal insufficiency or other risk factors. In patients after transplantation of organs receiving valaciclovir for the prevention of cytomegalovirus infection in high doses (8 g per day), neurological reactions occur more often than in those receiving lower doses.

On the part of the respiratory system and organs of the chest cavity: infrequently - shortness of breath.

On the part of the hepatobiliary system: very rarely - a reversible increase in the level of functional hepatic tests, sometimes regarded as hepatitis.

On the part of the skin and subcutaneous tissues: infrequently - skin rashes, including the effects of photosensitivity; rarely itching; very rarely - urticaria, angioedema.

On the part of the kidneys and urinary system: rarely - impaired renal function; very rarely, acute renal failure.

Others: there are reports of renal failure, microangiopathy, hemolytic anemia and thrombocytopenia (sometimes in combination) in severe patients with immunodeficiency, especially in patients with advanced HIV infection who received high doses (8 g per day) of valacyclovir for a long time.

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

Cimetidine and probenecid increase the AUC value of acyclovir by reducing its renal clearance, however, the need for dose adjustment is absent due to the wide therapeutic index of acyclovir.

Care should be taken when prescribing valaciclovir in high doses (4 g / day) to prevent cytomegalovirus infection at the same time with drugs that compete with sacyclovir for the route of elimination, since this may lead to an increase in blood levels of one or both drugs and their metabolites. When taken simultaneously with mycophenolate mofetil in blood plasma, the concentration of acyclovir and the inactive metabolite of mycophenolate mofetil increases. Caution should also be taken when administering high doses of valacyclovir and other drugs that affect kidney function (for example, cyclosporine, tacrolimus).

Inside (regardless of the meal).

For the treatment of herpes zoster adults appoint 1 g 3 times / day. within 7 days.

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

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

For the prevention (suppression) of relapses of infections caused by the Herpes simplex virus, adults with normal levels of immunity are prescribed in a dose of 500 mg 1 time / day. Adults with immunodeficiency are advised to take 500 mg 2 times / day. The duration of treatment is 4-12 months. Data on the prevention of infection in other populations of patients are not available.

In renal insufficiency, the dosage regimen is established depending on the creatinine clearance (CK) and indications.

IndicationsKK (ml / min) Dose of valaciclovir: herpes sore 15–30 ml / min1 g 2 times / day. Less than 15 ml / min1 g 1 time / day. Treatment of infections caused by Herpes simplexer than 15 ml / min500 mg 1 time / day. Treatment of labial herpes31 -49 ml / min. 1 g 2 times for 1 day, 15-30 ml / min, 500 mg 2 times / day. within 1 day less than 15 ml / min 500 mg one time Prevention (suppression) of infections caused by Herpessimplex less than 15 ml / min in a normal state of immunity: 250 mg 1 time / sutpri immunodeficiency: 500 mg 1 time / day For reducing infection with genital herpes less than 15 ml / min 250 mg 1 time / day

Patients on hemodialysis are advised to administer valacyclovir immediately after the end of the hemodialysis session in a dose intended for patients with a CC of 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 old, the recommended dose is 2 g 4 times / day. The drug is prescribed as soon as possible after the transplantation. The dose should be reduced depending on creatinine clearance (CC). The course duration is 90 days, but can be increased in patients with a high risk of developing infections.

Creatinine clearance (ml / min) Dose of valaciclovir ≥752 g 4 times / day.50 - <751.5 g 4 times / day.25 - <501.5 g 3 times / day.10 - <251.5 g 2 times / day. <10 or hemodialysis 1.5 g 1 time / day.

Frequent control of QC is needed, especially during the period when the kidney function is changing rapidly (including immediately after transplantation or transplant engraftment); dose of valacyclovir should be adjusted in accordance with CC.

Symptomatology
The occurrence 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 described cases of repeated overdose in patients with impaired renal function and in elderly patients were caused by an insufficient reduction in the dose of the drug.

Treatment
Patients should be carefully monitored for the timely diagnosis of toxic manifestations. Hemodialysis significantly speeds up the excretion of acyclovir from the blood and can be considered the best way of treatment in case of symptomatic overdose.

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

Registered data on the outcome of pregnancy in women who took valacyclovir or acyclovir, which is an 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 valaciclovir during pregnancy, reliable and definite conclusions about the safety of valaciclovir during pregnancy cannot be made.

Acyclovir, the main metabolite of valaciclovir, is excreted in breast milk. After taking valacyclovir orally at a dose of 500 mg Cmax of acyclovir in breast milk, it was 0.5-2.3 times (on average 1.4 times) higher than the corresponding concentrations of acyclovir in the mother's blood plasma. The ratio of the area under the concentration-time curve (AUC) in the blood plasma of acyclovir in breast milk to the area under the concentration-time curve (AUC) of acyclovir in the mother's plasma ranged from 1.4 to 2.6 (average 2, 2).The average concentration of acyclovir in breast milk was 2.24 mcg / ml (9.95 mcg / M). When a mother takes Valaciclovir orally at a dose of 500 mg 2 times / day. the child will be exposed to the same effects of acyclovir as when taken 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 that from blood plasma. Valaciclovir in unchanged form was not detected in the plasma of the mother, breast milk or in the urine of the child.

During breastfeeding, the drug is used only if the intended benefit to the mother outweighs the potential risk to the baby. Given this, it is necessary to carefully appoint valaciclovir to the mother during lactation (breastfeeding). However, intravenous (IV) administration of acyclovir at a dose of 30 mg / kg / day. used in newborns for the treatment of diseases caused by the herpes simplex virus.

In experimental studies, valaciclovir had no teratogenic effects in rats and rabbits. Subcutaneous (sc) administration of acyclovir in the generally accepted tests for teratogenicity did not cause teratogenic effects in rats and rabbits. In additional studies in rats, fetal developmental disorders were detected by SC injection of the drug in doses that caused an increase in the plasma concentration of acyclovir to 100 μg / ml and toxic effects in the mother's body.

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

Hydration. Elderly patients, people with dehydration during treatment with valaciclovir need to increase the amount of fluid consumed. In the absence of pronounced impaired renal function, dosing regimen adjustment is not required.

Use in violation of kidney function and in elderly patients. Valacyclovir is excreted through the kidneys, in connection with this elderly patient with the likelihood of reduced renal function, it is necessary to reduce the dose of the drug. In patients with a history of renal disease, the risk of nephrological complications increases, and such patients should be closely monitored for timely detection.

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

Lactation period. It is recommended that valaciclovir be prescribed with caution to women during breastfeeding.

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

In the event of side effects from the central nervous system (including agitation, hallucinations, confusion, delusions, seizures and encephalopathy), the drug is canceled.

Film Coated Tablets

At a temperature not higher than 30 ° C

3 years

On prescription