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

Active substance:
Valaciclovir hydrochloride (in terms of valaciclovir)	556.0 mg 500 mg
Excipients:
Microcrystalline cellulose	87.0 mg
Povidone (K 90)	22.0 mg
Kollidone (crospovidone CL)	28.0 mg
Calcium stearate	7.0 mg
Composition of the film shell:
Aquarius Prime VAR218010 white [hypromellose - 65%, titanium dioxide -25%, macrogol - 10%] (Ph Eur, USP)	25.0 mg

Description:The tablets covered with a film cover of white color, round, biconcave form. On the cross-section, two layers are visible, 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:

Specific inhibitor of DNA polymerase of herpes viruses. It blocks the synthesis of viral DNA and the replication of viruses. In the human body is transformed into acyclovir and L-valine; As a result of phosphorylation from acyclovir, an active acyclovirtriphosphate is formed, which competitively suppresses the viral DNA polymerase. The first stage of phosphorylation occurs under the influence of the virus-specific enzyme (for Herpes simplex, Varicella zoster, the Epstein-Barr virus is a 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.

Active in vitro against viruses Herpes simplex 1 and 2 types, virus Varicella zoster, Epstein-Barr virus, CMV and human herpesvirus type 6.

Pharmacokinetics:

Absorption - high, quickly and almost completely turns into acyclovir and L-valine.Bioavailability of acyclovir when taking 1 g of valacyclovir is 54% (3-5 times higher than when taking acyclovir inwards). After using valaciclovir in a dose of 3 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_max) after a single intake of 1 g - 15-25 μmol / ml, the time to reach the maximum concentration (TC_max) 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 body tissues and fluids, including the brain, kidneys, lungs, liver, lacrimal fluid, intestines, muscles, spleen, uterus, mucous membrane and vaginal secretion, sperm, amniotic fluid, cerebrospinal fluid (CSF) (50% of concentration in plasma), a liquid of herpetic vesicles. The highest concentrations are created in the kidneys, liver and intestines. Penetrates through the placenta and into breast milk.

The half-life (T_1/2) valaciclovir - less than 30 min; Acyclovir 2.5-3.3 hours, with the terminal stage of renal failure -14 hours, in elderly patients (65-83 years) - 3,3-3,7.

It is excreted by the kidneys (45,6%), mainly in the form of acyclovir and its metabolite 9-carboxymethoxymethylguanine, less than 1% - unchanged and through the intestine (47.12%) for 96 hours.

Indications:

In adults: shingles, skin and mucous membrane diseases caused by the virus Herpes simplex (including genital herpes), prevention of recurrence of diseases caused by the virus Herpes simplex.

In adults and children from the age of 12: prevention of cytomegalovirus infection in organ transplantation.

Contraindications:

Hypersensitivity, bone marrow transplantation, clinically expressed forms of HIV infection, kidney transplantation, 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, pregnancy, lactation.

Pregnancy and lactation:

There are limited data on the use of valacyclovir in pregnancy. Use is only possible in cases where the potential benefit to the mother exceeds the possible risk to the fetus.

Valacyclovir in unchanged form was not determined in the plasma of the mother, breast milk. Acyclovir, the main metabolite of valacyclovir, excreted in breast milk. Given this, caution should be exercised valaciclovir mother during lactation.

Dosing and Administration:

Inside.

For the treatment of herpes zoster

Adults

1 g 3 times a day for 7 days.

Treatment of infections caused by the herpes simplex virus

Adults

500 mg twice a day. With recurrence of diseases caused by the virus Herpes simplex, treatment begins in the prodromal period or immediately after the appearance of the first symptoms and continues for 3-5 days; in more severe cases, if necessary, at the first stage, the duration of treatment is increased to 10 days.

Prevention (suppression) of recurrences of infections caused by the herpes simplex virus

Adults

In patients with preserved immunity, 500 mg once a day. In patients with frequent relapses (10 or more per year), an additional effect can be achieved with a daily dose of 500 mg divided into 2 divided doses (250 mg twice daily).

For patients with immunodeficiency, the recommended dose is 500 mg twice a day.

Correction of the dosing regimen in renal failure (depending on the creatinine clearance - KK) in the treatment of herpes zoster, herpes simplex (treatment and prevention)

Indications	KK (ml/min)	Dose
Shingles Herpes
	15-30	1 g 2 times a day
	less than 15	1 g once a day
Herpes simplex (treatment)	less than 15	500 mg once a day
Herpes simplex (prevention)
- Patients with preserved immunity	less than 15	250 mg once a day
- patients with immunodeficiency	less than 15	500 mg once a day

In patients on hemodialysis, it is recommended to take the drug immediately after the end of the hemodialysis session, at the same dose as in patients with SC less than 15 ml / min.

Prevention of cytomegalovirus infection

Adults and children over 12 years

The recommended dose is 2 g 4 times a day, as soon as possible after transplantation.

The course of treatment is 90 days, if necessary, treatment can be longer.

Correction of the dosage regimen depending on the QC value in the prevention of cytomegalovirus infection

CK (ml / min)	Dose
75 and more	2 g 4 times a day
50-75	1.5 g 4 times a day
25-50	1.5 g 3 times a day
10-25	1.5 g 2 times a day
Less than 10 or hemodialysis	1.5 grams once a day

Patients on hemodialysis are recommended to take the drug immediately after the end of the hemodialysis session. It is necessary to regularly monitor the clearance of creatinine, especially immediately after transplantation and engraftment of the graft.

With hepatic insufficiency (incl.on the background of cirrhosis of the liver of mild or moderate severity) correction of the dose is not required. Pharmacokinetic data in patients with severe cirrhosis of the liver also do not support the need for dose adjustment, however, clinical experience with this pathology is limited.

In elderly patients correction of the dose is required only in case of renal dysfunction (see the corresponding tables).

Side effects:

From the digestive system: nausea, abdominal pain, vomiting, diarrhea, increased activity of "liver" enzymes, hepatitis.

From the nervous system: headache, fatigue, dizziness, confusion or depression, hallucinations, coma.

Side effects from the nervous system usually develop in patients with impaired renal function or other predisposing factors. In patients receiving high doses of valacyclovir (prevention of cytomegalovirus infection), neurologic side effects are more common.

From the urinary system: acute renal failure.

From the hematopoiesis: thrombocytopenia, microangiopathic hemolytic anemia.

From the skin: rash, itching, hives, photosensitivity.

Allergic reactions: angioedema, anaphylactic reactions.

Overdose:

Symptoms: perhaps deposition of acyclovir in the renal tubules, with the development of acute renal failure and anuria.

Treatment: hemodialysis.

Interaction:

Cimetidine and tubular secretion blockers reduce the effect (reduce the rate, but not the completeness of conversion into acyclovir).

Nephrotoxic drugs increase the risk of developing nephrotoxicity and disorders from the central nervous system.

Special instructions:

In patients with normal immunity, viruses with reduced sensitivity are extremely rare; relatively more often these viruses are found in people with severe immunodeficiency (in recipients of internal organs or bone marrow, patients receiving chemotherapy for malignant neoplasms infected with HIV). Reduced sensitivity of viruses to the drug is due to the phenotypic deficiency of thymidine kinase in cells infected with the virus, while the virulence of such viruses is close to that of "wild" viruses.

Older patients in the period of treatment need to increase the amount of fluid consumed.

In the absence of severe renal dysfunction, correction of the dosing regimen is not required.

The experience of using the drug in children is not enough.

When treating genital herpes, sexual intercourse should be avoided. the drug does not protect against transmission of infection.

The use of the drug in high doses for a long time under 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.

Form release / dosage:

Tablets, film-coated, 500 mg.

Packaging:

10 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil.

For 10, 42 tablets in a can of polymer.

A jar or one contour mesh package together with an instruction for use is placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place 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:LSR-002798/10

Date of registration:02.04.2010 / 26.07.2013

Expiration Date:Unlimited

The owner of the registration certificate:TECHNOLOGY OF DRUGS, LTD. TECHNOLOGY OF DRUGS, LTD. Russia

Manufacturer: & nbsp

TECHNOLOGY OF DRUGS, LTD. Russia

Information update date: & nbsp14.01.2017

Illustrated instructions

Instructions

Valaciclovir (Valacyclovir)