Wirdel - instructions for use, dose, side effects, contraindications

active substance: valaciclovir hydrochloride monohydrate 583.8 mg (from 573.0 to 591.0 mg), calculated as valacyclovir hydrochloride 556.0 mg, calculated as valaciclovir 500.0 mg;

Excipients: cellulose microcrystalline from 37.0 to 55.0 mg, crospovidone 15.0 mg, povidone (Kollidon 90 E) 50.0 mg, magnesium stearate 7.0 mg;

sheath (Deficient white YS-1-7003: titanium dioxide 31.250%, hypromellose (3 cP, 6 cP) 29.875%. macrogol (polyethylene glycol 400) 8,000%, polysorbate (tweep 80) 1,000%) - 17.5 mg.

Description:

Tablets covered with a film coat of white or almost white color, capsular, biconvex. On one side is engraved "V", on the other "500". The core of the tablet is white or almost white.

Pharmacotherapeutic group:Antiviral agent

ATX: & nbsp

J.05.A.B.11 Valaciclovir

J.05.A.B Nucleosides and nucleotides

Pharmacodynamics:

Antiviral drug. Specific nucleoside inhibitor of DNA polymerase of herpes viruses. In the human body quickly turns into a acyclovir and L-valine; As a result of phosphorylation from acyclovir, an active acyclovirtriphosphate is formed that competitively suppresses the viral DNA polymerase and, being an analogue of the purine nucleoside (guanine), is inserted into the viral DNA, resulting in complete chain breakage, discontinuation of DNA synthesis and blockage of viral replication. The first stage of phosphorylation occurs under the influence of the virus-specific enzyme (for viruses Herpes simplex 1 and 2 types, Varicella zoster - viral thymidine kinase, which is found only in cells infected with the virus).For cytomegalovirus (CMV), the selectivity of the drug is due to the fact that phosphorylation is partially mediated by the product of the phosphotransferase gene UL97. The drug is active in vitro for herpes simplex virus (HSV) 1 and 2 types, herpes zoster virus, Epstein-Barr virus, CMV and human herpesvirus type 6.

In patients with preserved immunity, viruses Herpes simplex and Varicella zoster with reduced sensitivity to valaciclovir are extremely rare (less than 0.1%), but can sometimes be found in patients with severe impairment of immunity, for example, with bone marrow transplant, in chemotherapy for malignant neoplasms and in HIV-infected patients.

Pharmacokinetics:

After oral administration, it is well absorbed from the gastrointestinal tract. With the participation of the enzyme of the liver, valaciclovirhydrolase quickly and almost completely turns into acyclovir and L-valine. Bioavailability (in terms of acyclovir) when taken in a dose of 1000 mg is 54% and does not depend on food intake. After using valaciclovir in a dose of 1 g 4 times a day, the area under the concentration-time curve (AUC) is approximately equal to AUC with intravenous administration of acyclovir in a dose of 5 mg every 8 hours. The maximum concentration in plasma (C_mOh) after a single dose of 1 g -15-25 μmol / ml, the time to reach C_mOh- 1,6-2,1 hours; 3 hours unmetabolized valaciclovir in plasma is not determined. The connection with plasma proteins valacyclovir - 13-18%, acyclovir - 9-33%.

Acyclovir is widely distributed in tissues and body fluids, including the brain, liver, uterus, mucous membrane and vaginal secretion, sperm, cerebrospinal fluid (50% of the concentration in the plasma), and herpetic vesicle fluid. Penetrates through the placenta and into breast milk. Metabolism valaciclovir / acyclovir is not associated with cytochrome P450 enzymes.

After repeated use of valaciclovir in patients with normal renal function acyclovir Do not cumulate. Half-life (T_1/2) valaciclovir in patients with normal renal function - less than 30 minutes; Acyclovir 2.5-3.3 hours, with the terminal stage of chronic renal failure (CRF) - 14 hours, in elderly patients (65-83 years) - 3,3-3,7 hours.

It is excreted by the kidneys (45.6%), mainly in the form of acyclovir (more than 80% of the dose) and its metabolite 9-carboxymethoxymethylguanine, less than 1% - unchanged; and through the intestine (47.12%) for 96 hours.In patients on hemodialysis, T_1/2about 4 hours; During the 4-hour procedure, about 30% of the drug is removed. With peritoneal dialysis, the drug is removed to a lesser extent.

Indications:

Adults:

- Treatment of herpes zoster (Herpes zoster).

- Treatment of infections of the skin and mucous membranes caused by HSV type 1 and 2 (including newly diagnosed genital herpes, recurrent genital herpes (Herpes genitalis) and labial herpes (Herpes labialis).

- Prevention (suppression) of recurrences of infections of the skin and mucous membranes caused by HSV type 1 and 2 (including genital herpes).

- Reducing the risk of transmission of genital herpes to a healthy partner.

Adults and adolescents 12 years and older:

- Prevention of cytomegalovirus infection that occurs during organ transplantation.

Contraindications:

Hypersensitivity to valaciclovir, acyclovir, and to other components included in the preparation; HIV infection with content Cd4 + - lymphocytes less than 100 / μL; Children's age (up to 12 years - for the prevention of cytomegalovirus infection during organ transplantation, up to 18 years - for other indications).

Carefully:

Hepatic / renal failure,clinically expressed forms of HIV infection; pregnancy, lactation; elderly age; hypohydration, simultaneous use of nephrotoxic drugs.

Pregnancy and lactation:

There are limited data on the use of valacyclovir in pregnancy. Valaciclovir apply only in cases where the potential benefit to the mother exceeds the possible risk to the fetus. Registered data on the outcome of pregnancy in women who took valaciclovir or acyclovir, did not show an increase in the number of birth defects in their children compared to the general population. Because the register includes a small number of women who valaciclovir when pregnancy, it is impossible to make reliable and definite conclusions about the safety of valaciclovir during pregnancy.

Acyclovir, the main metabolite of valacyclovir, is excreted in breast milk. When the mother valacyclovir is taken inside at a dose of 500 mg 2 times / day, the child will undergo the same effect of acyclovir as if taking it inside at a dose of about 0.61 mg / kg / day. The half-life of acyclovir from breast milk is the same as from plasma. Valaciclovir in unmodified form was not determined in the plasma of the mother, breast milk or in the urine of the child. Valaciclovir should be administered with caution to lactating women. However, intravenous administration of acyclovir at a dose of 30 mg / kg / day is used in neonates for the treatment of diseases caused by the herpes simplex virus.

Dosing and Administration:

Inside, regardless of food intake.

Treatment of herpes zoster (treatment is recommended to begin when the first symptoms appear).

Adults: 1000 mg 3 times a day for 7 days.

Treatment of infections caused by HSV (treatment is recommended to begin in the prodromal period or when the first symptoms appear).

Adults: 500 mg twice a day. With relapse of herpes, the course of treatment is 3-5 days; if necessary, the course of treatment can be extended to 10 days.

When labial herpes it is also possible to take valaciclovir in a dose of 2 g twice a day (the second dose should be taken after approximately 12 hours, but not earlier than 6 hours after the first dose); course of treatment -1 day. Treatment is recommended to begin with the earliest symptoms of labial herpes, such as tingling, itching, burning.

Prevention (suppression) of recurrences of infections caused by HSV

Adults

Patients from normal immune status: 500 mg once a day.

Patients from immunodeficiency: 500 mg twice a day.

Reducing the risk of transmission of genital herpes to a healthy partner

To reduce the risk of transmission of genital herpes to a healthy partner the heterosexual adult patients with preserved immunity and with the number of exacerbations to 9 per year: 500 mg once a day for a year or more every day with regular sexual intercourse. Data on the prevention of infection in other populations of patients are absent.

Prevention of cytomegalovirus infection after transplantation

Adults and adolescents aged 12 years and over: 2 g 4 times a day. It is recommended to start treatment as early as possible after transplantation. The dose should be reduced depending on the creatinine clearance. The course of treatment is 90 days (in patients with a high risk of developing infections can be extended).

Have elderly patients no dose adjustment is required, except for a significant impairment of renal function.

When chronic renal failure (CRF) the dosage regimen is set depending on the creatinine clearance (CK) and the indications.

Treatment of shingles: KK 15-30 ml / min - 1 g 2 times a day; KK less than 15 ml / min - 1 g once a day.

Treatment of infections caused by HSV: KK less than 15 ml / min - 500 mg once a day.

Treatment of labial herpes: KK 31-49 ml / min - 1 g 2 times a day for 1 day; KK 15-30 ml / min - 500 mg twice a day for one day; KK less than 15 ml / min - 500 mg once.

Prevention (suppression) of recurrences of infections caused by HSV

Adult patients from normal immune status: KK less than 15 ml / min - 250 mg each 1 once a day.

Adult patients from immunodeficiency: KK less than 15 ml / min - 500 mg once a day. Reducing the risk of transmission of genital herpes to a healthy partner: KK less than 15 ml / min - 250 mg once a day.

Prevention of cytomegalovirus infection after transplantation

Adults and adolescents aged 12 years and over: KK 75 ml / min and more - 2 g 4 times a day; KK from 50 to less than 75 ml / min - 1,5 g 4 times a day; KK from 25 to less than 50 ml / min - 1,5 g 3 times a day; KK from 10 to less than 25 ml / min - 1,5 g 2 times a day; KK less than 10 ml / min or in patients on hemodialysis - 1.5 g once a day. Patients who are on hemodialysis, the drug is recommended to be taken immediately after the procedure of hemodialysis at the same dose as patients with CC less than 15 ml / min.

Patients with impaired hepatic function

In patients with mild or moderate liver cirrhosis (the synthetic function of the liver is preserved), dose adjustment is not required. In the study of pharmacokinetics in patients with severe cirrhosis of the liver (with a violation of the synthetic function of the liver and the presence of shunts between the portal system and the common vascular bed), there was also no evidence of a need for correction of the dosing regimen; However, the clinical experience of valaciclovir in this category of patients is organic.

Side effects:

The frequency of the following possible side effects is indicated in accordance with the classification of the World Health Organization: Often (≥ 10%), often (≥ 1% and <10%), infrequently (≥ 0.1% and <1%), rarely (≥0.01% and <0.1%), rarely (<0.01%, including individual cases).

From the side of the central nervous system: often headache: rarely - dizziness, confusion, hallucinations, depression of consciousness; rarely - agitation, tremor, ataxia, dysarthria, psychotic symptoms, convulsions, encephalopathy, coma.The listed symptoms are reversible and are usually observed in patients with impaired renal function or against a background of other predisposing conditions. In adult patients with a transplanted organ who receive high doses (8 g per day) of valaciclovir for the prevention of CMV infection, neurologic reactions develop more often than with lower doses.

From the respiratory system: infrequently - shortness of breath.

From the digestive system: often - nausea; rarely - discomfort in abdomen, vomiting, diarrhea; rarely - reversible violations of functional liver samples, which are sometimes regarded as manifestations of hepatitis.

From the skin and subcutaneous fat: infrequently - skin rash, photosensitivity: rarely - itching.

Allergic reactions: very rarely - anaphylaxis. rarely - hives, angioedema.

From the urinary system: infrequently - hematuria (often associated with other disorders of the kidneys); rarely - impaired renal function; rarely - acute renal failure, renal colic (renal colic may be associated with impaired renal function).Cases of precipitation of acyclovir crystals in the lumen of renal tubules have been reported. Adequate drinking regimen should be observed during treatment.

On the part of the organs of hematopoiesis: rarely -leukopenia, thrombocytopenia.

Other: in patients with severe impairment of immunity, especially in adult patients in the late stage of acquired immune deficiency syndrome (AIDS) receiving valaciclovir in high doses (8 g / day daily) for a long time, there were cases of renal failure, microangiopathic hemolytic anemia and thrombocytopenia (sometimes in combination). Similar complications were observed in patients with the same diseases, but not receiving valaciclovir.

Overdose:

Symptoms: acute renal failure and disorders of the central nervous system (confusion, hallucinations, agitation, convulsions, coma); nausea and vomiting are possible.

Treatment: Hemodialysis (with acute renal failure and anuria).

Interaction:

Clinically significant interactions are not established.

Acyclovir is excreted by the kidneys. mainly in an unchanged form through active renal secretion.Combined use of drugs with this removal mechanism can lead to an increase in the concentration of acyclovir in the blood plasma. After the appointment of valaciclovir in a dose of 1000 mg and drugs cimetidine, probenecid, which are derived in the same way as valaciclovir, there is an increase in AUC of acyclovir and, thus, decreases the renal clearance of acyclovir. However, due to the wide therapeutic index of acyclovir, dose adjustment of valacyclovir is not required.

In the treatment of labial herpes, the prevention and treatment of diseases caused by CMV, caution should be exercised in case of simultaneous use of valaciclovir in higher doses (4000 mg per day or more) and drugs that compete with acyclovir for the route of excretion. because there is a potential threat of an increase in plasma concentrations of one or both drugs or their metabolites. There was an increase in the AUC of acyclovir and the inactive metabolite of mycophenolate mofetil (an immunosuppressant used in patients after organ transplantation) with the simultaneous use of these drugs.

The simultaneous use of valaciclovir with nephrotoxic drugs, including aminoglycosides, organic compounds of platinum, iodinated contrast medium, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus should be performed with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function.

Special instructions:

In patients at risk of dehydration, especially in elderly patients, adequate water-electrolyte balance should be maintained.

It is recommended to closely monitor patients with impaired renal function and elderly patients due to a higher risk of developing central nervous system (CNS) adverse events, acute renal failure and the risk of overdose in this category of patients.

In patients with chronic renal failure, creatinine clearance is often recommended, especially when the kidney function changes rapidly (in particular immediately after transplantation or transplant engraftment), and the valaciclovir dose is adjusted according to the creatinine clearance.In the absence of severe renal dysfunction, correction of the dosing regimen is not required.

It is necessary to use caution valaciclovir (especially at doses exceeding 4 mg per day) concomitantly with drugs that compete with acyclovir for the pathway of elimination, as well as with drugs that disrupt kidney function. There is no data on the use of valaciclovir in high doses (4 g per day or more) in patients with liver disease, so caution should be given to the drug in high doses of this category of patients.

Valacyclovir reduces the risk of transmission of genital herpes in heterosexual adult patients with preserved immunity. Data on the prevention of infection in other populations of patients are absent.

Valacyclovir reduces the risk of transmission of genital herpes, but does not exclude it completely and does not lead to complete cure. During valaciclovir therapy, the patient should take measures to ensure the safety of the partner during sexual intercourse.

Reception of the drug in high doses for a long time in conditions accompanied by severe immunodeficiency (bone marrow transplantation, clinically expressed forms of HIV infection,kidney transplantation), led to the development of thrombocytopenic purpura and hemolytic-uremic syndrome, up to a lethal outcome.

When there are side effects from the central nervous system (including agitation, hallucinations, confusion, delusions, convulsions and encephalopathy), the drug is canceled.

Effect on the ability to drive transp. cf. and fur:When assessing a patient's ability to control a car and other mechanisms, the patient's clinical condition and the side-effects profile of valaciclovir should be taken into account.

Form release / dosage:

Tablets, film-coated, 500 mg.

Packaging:

For 10 or 14 tablets in a planar cell pack of a polyvinylchloride film and aluminum foil.

1 contour pack of 10 tablets or 3 contour packs of 14 tablets together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000666

Date of registration:28.09.2011 / 15.10.2015

Expiration Date:28.09.2016

Date of cancellation:2016-09-28

The owner of the registration certificate:NIZHFARM, JSC NIZHFARM, JSC Russia

Manufacturer: & nbsp

HETERO LABS, Limited India

Representation: & nbspNizhpharm, JSCNizhpharm, JSCRussia

Information update date: & nbsp19.02.2017

Illustrated instructions

Instructions

Wirdel (Virdel)