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

The antiviral drug is a synthetic analogue of the acyclic purine nucleoside, which has a highly selective effect on herpes viruses.In viral infected cells under the action of viral thymidine kinase, phosphorylation occurs and further sequential transformation of acyclovir into mono-, di- and triphosphate occurs. Acyclovir triphosphate is inserted into the viral DNA chain and blocks its synthesis by competitive inhibition of the viral DNA polymerase.

In vitro Acyclovir is effective against herpes simplex virus - Herpes simplex 1 and 2 types; against the virus Varicella zoster, causing varicella and shingles; higher concentrations are required to inhibit the Epstein-Barr virus. Moderately active against cytomegalovirus.

In vivo Acyclovir is therapeutically and prophylactically effective, especially in viral infections caused by the virus Herpes simplex. It prevents the formation of new elements of the rash, reduces the likelihood of cutaneous dissemination and visceral complications, accelerates the formation of crusts, reduces pain in the acute phase of herpes zoster.

Pharmacokinetics:

After oral administration, the bioavailability is 15-30%, and dose-dependent concentrations are created sufficient to effectively treat viral diseases.Food has no significant effect on the absorption of acyclovir. Acyclovir well penetrates into many organs, tissues and body fluids. Binding to plasma proteins is 9-33% and does not depend on its concentration in the plasma. The concentration in the cerebrospinal fluid is about 50% of its concentration in the plasma. Acyclovir penetrates the hemato-encephalic and placental barriers, accumulates in breast milk. After ingestion 1 g / day. the concentration of acyclovir in breast milk is 60 to 410% of its concentration in the plasma (in the body of a child with milk of the mother acyclovir comes in a dose of 0.3 mg / kg / day).

The maximum concentration of the drug in the blood plasma (C_m_Oh) after oral administration 200 mg 5 times a day - 0,7 mkg / ml, the minimum concentration (C_min) 0.4 μg / ml; time to reach the maximum concentration of the drug in plasma (TC_m_Oh) - 1,5-2 hours. Metabolised in the liver to form a pharmacologically inactive compound 9-carboxymethoxymethylguanine. It is excreted by the kidneys through glomerular filtration and tubular secretion: about 84% is excreted by the kidneys unchanged, 14% - in the form of a metabolite. Aciclovir renal clearance is 75-80% of the total plasma clearance. Half-life (T_1/2) in adults with normal kidney function is 2-3 hours.In patients with severe renal failure, the half-life is 20 hours, with hemodialysis - 5.7 hours, while the concentration of acyclovir in the plasma decreases to 60% of the initial value. Less than 2% of acyclovir is excreted from the body through the intestine.

Indications:

1 Treatment of infections of the skin and mucous membranes caused by viruses Herpes simplex 1 and 2 types, both primary and secondary, including genital herpes;

2 prevention of exacerbations of recurrent infections caused by viruses Herpes simplex 1 and 2 types, in patients with normal immune status;

3 prevention of primary and recurrent infections caused by viruses Herpes simplex 1 and 2 types, in patients with immunodeficiency;

4 in the complex therapy of patients with severe immunodeficiency: in HIV infection (stage of AIDS, early clinical manifestations and a developed clinical picture) and in patients who underwent bone marrow transplantation;

5 treatment of primary and recurrent infections caused by the virus Varicella zoster (chicken pox, as well as shingles - Herpes zoster).

Contraindications:

Hypersensitivity to acyclovir, ganciclovir or any auxiliary substance of the drug.

Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

The drug is contraindicated during lactation.

Children under 3 years (for this dosage form).

Carefully:

Pregnancy; elderly patients and patients taking large doses of acyclovir, especially against dehydration; impaired renal function; neurological disorders or neurological reactions to the administration of cytotoxic drugs (including in the anamnesis).

Pregnancy and lactation:

Acyclovir penetrates the placental barrier and accumulates in breast milk. The use of the drug during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus. If you need to take acyclovir during lactation, interruption of breastfeeding is required.

Dosing and Administration:

Acyclovir is taken during or immediately after a meal and washed down with a sufficient amount of water. The dosage regimen is set individually, depending on the severity of the disease.

Treatment of infections of the skin and mucous membranes caused by Herpes simplex 1 and 2 types:

Adults: Acyclovir is prescribed 200 mg 5 times a day for 5 days with 4 hour intervals during the day and with an 8 hour interval at night. In more severe cases of the disease, the course of treatment can be extended to the doctor's prescription up to 10 days. As part of complex therapy for severe immunodeficiency, including, with a developed clinical picture of HIV infection, including early clinical manifestations of HIV infection and the stage of AIDS; after bone marrow transplantation or when there is a violation of absorption from the intestine, 400 mg 5 times a day are prescribed.

Treatment should be started as soon as possible after the onset of infection; at relapses acyclovir prescribe in the prodromal period or with the manifestation of the first elements of the rash.

Prevention of recurrence of infections caused by Herpes simplex 1 and 2 types in patients with normal immune status - The recommended dose is 200 mg 4 times a day (every 6 hours) or 400 mg twice a day (every 12 hours). In some cases, lower doses are effective - 200 mg 3 times a day (every 8 hours) or 2 times a day (every 12 hours).

Prevention of infections caused by Herpes simplex 1 and 2 types, in patients with immunodeficiency - The recommended dose is 200 mg 4 times a day (every 6 hours).

In case of severe immunodeficiency (for example, after bone marrow transplantation) or if absorption is violated from the intestine, the dose is increased to 400 mg 5 times a day. The duration of the preventive course of therapy is determined by the duration of the infection risk period.

Treatment of infections caused by the virus Varicella zoster (chickenpox)

Adults: prescribe 800 mg 5 times a day every 4 hours in the afternoon and with an 8-hour interval at night. Duration of treatment 7-10 days.

Children: prescribe 20 mg / kg 4 times a day for 5 days (maximum single dose 800 mg), children from 3 to 6 years: 400 mg 4 times a day, over 6 years: 800 mg 4 times a day for 5 days.

Treatment should be started when the earliest signs or symptoms of chicken pox appear.

Treatment of infections caused by the virus Herpes zoster (shingles) Adults: prescribe 800 mg 4 times a day every 6 hours for 5 days.

Children aged 3 years and over

Treatment and prevention of infections caused by Herpes simplex 1 and 2 types, children of children age with immunodeficiency and normal immune status: from 3 years to 6 years - 400 mg 4 times a day; over 6 years - 800 mg 4 times a day.

A more accurate dose is determined from the calculation of 20 mg / kg body weight, but not more than 800 mg 4 times a day. The course of treatment is 5 days.

Data on the prevention of recurrence of infections caused by the herpes simplex virus and the treatment of herpes zoster in children with normal immunity parameters are absent.

Treatment of pediatric patients with severe immunodeficiency: for Treatment of children older than 3 years prescribed 800 mg of acyclovir 4 times a day every 6 hours (as for the treatment of adults with immunodeficiency).

Elderly patients

In the elderly, there is a decrease in clearance of acyclovir in the body in parallel with a decrease in creatinine clearance. Older patients taking Large doses of the drug inside should receive a sufficient amount of liquid. In case of renal insufficiency, it is necessary to solve the problem of reducing the dose of the drug.

Patients with renal insufficiency

Care must be taken when administering acyclovir to patients with renal insufficiency. In such patients, oral administration at recommended doses for the treatment and prevention of infections caused by the herpes simplex virus does not lead to cumulation of the drug to concentrations exceeding the established safe levels.However, in patients with severe renal failure (creatinine clearance (CK) less than 10 ml / min), the dose of acyclovir should be reduced to 200 mg 2 times a day with 12-hour intervals.

In the treatment of infections caused by the virus Varicella zoster, Herpes zoster, as well as in the treatment of patients with severe immunodeficiency, the recommended dose is:

1 terminal renal failure (creatinine clearance less than 10 ml / min) - 800 mg twice a day every 12 hours;

2 severe renal failure (clearance of creatinine 10-25 ml / min) - 800 mg 3 times a day every 8 hours.

Side effects:

The drug is usually well tolerated.

The following classification of undesirable reactions is used depending on the frequency of occurrence: very often (> 1/10), often (<1/100, <1/10), sometimes (> 1/1000, <1/100), rarely (> 1 /10.000, <1/1000), very rarely (<1 / 10,000).

From the gastrointestinal tract: often - nausea, vomiting, diarrhea; very rarely - hepatitis, jaundice; in isolated cases - abdominal pain.

In blood: rarely - a transient slight increase in the activity of liver enzymes, a slight increase in the concentration of urea and creatinine, hyperbilirubinemia, very rarely - leukopenia, erythropenia, anemia, thrombocytopenia.

From the central nervous system: often - headache, dizziness; very rarely - agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, drowsiness, encephalopathy, coma. Usually, these side effects were observed in patients with renal insufficiency or in the presence of other provoking factors, and were, in general, reversible.

From the respiratory system: rarely - shortness of breath.

Allergic reactions: anaphylactic reactions, skin rash, itching, hives, Lyell's syndrome, Stevens-Johnson syndrome.

From the skin and subcutaneous tissue: often - itching, hives, rash, including sensitization; rarely - alopecia, rapid diffuse hair loss (since this type of alopecia is observed in various diseases and in the treatment of many drugs, its association with acyclovir is not established); very rarely - Lyell's syndrome, Stevens-Johnson syndrome.

Other: often fatigue, fever; rarely - peripheral edema, visual impairment, lymphadenopathy, myalgia, malaise.

Overdose:

There have been no cases of overdose with oral administration of acyclovir. It was reported that 20 g of acyclovir was ingested.Symptoms: agitation, coma, cramps, lethargy. It is possible to precipitate acyclovir in the renal tubules if its concentration exceeds the solubility in the renal tubules (2.5 mg / ml).

Treatment: symptomatic.

Interaction:

Simultaneous application with probenecid results in an increase in the mean half-life and a decrease in the clearance of acyclovir.

With simultaneous admission with nephrotoxic drugs, the risk of developing renal dysfunction increases.

Special instructions:

Provirosan ® is used strictly according to the doctor's prescription in order to avoid complications in adults and children over 3 years old.

Long-term or repeated treatment with acyclovir patients with reduced immunity can lead to the appearance of strains of viruses that are insensitive to its action. The majority of isolated strains of viruses, insensitive to acyclovir, show a relative lack of viral thymidine kinase; strains with altered thymidine kinase or with altered DNA polymerase were isolated. In vitro action of acyclovir on isolated strains of the virus Herpes simplex may cause the appearance of less sensitive strains.

With caution, the drug is prescribed for patients with impaired renal function, elderly patients due to an increase in the half-life of acyclovir.When using the drug, it is necessary to ensure the supply of a sufficient amount of liquid.

When taking the drug should monitor the function of the kidneys (the concentration of blood urea and blood plasma creatinine).

Acyclovir does not prevent sexual transmission of herpes, therefore during treatment it is necessary to abstain from sexual intercourse, even in the absence of clinical manifestations.

It is necessary to inform patients about the possibility of transmission of the virus of genital herpes in the period of rashes, as well as cases of asymptomatic virus carrying.

Effect on the ability to drive transp. cf. and fur:

No data.

However, it should be borne in mind that dizziness may develop during acyclovir treatment, therefore, care must be taken when driving vehicles and engaging in other potentially dangerous activities requiring increased attention and speed of psychomotor reactions. (See the "Side effect" section).

Form release / dosage:

Tablets 200 mg.

Packaging:

For 10 tablets in a blister of PVC / aluminum foil.

3 blisters in a cardboard pack together with instructions for use.

Storage conditions:

List B.In dry, dark place at a temperature of 15-25 ° C.

Keep out of the reach of children!

Shelf life:

3 years.

Do not use after the expiration date!

Terms of leave from pharmacies:On prescription

Registration number:П N014690 / 01

Date of registration:12.12.2008

The owner of the registration certificate:PRO.MED.CS Prague as.PRO.MED.CS Prague as. Czech Republic

Manufacturer: & nbsp

PRO.MED.CS Praha, a.s. Czech Republic

Representation: & nbspPRO.MED.CS Prague as. PRO.MED.CS Prague as. Czech Republic

Information update date: & nbsp25.08.2010

Illustrated instructions

Instructions

Provirsan® (Provirsan®)