Vairova, 500 mg 10 pcs

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. It blocks the synthesis of viral DNA and viral replication. In the human body valacyclovir is converted to acyclovir and valine.

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

Pharmacokinetics

After oral administration valacyclovir is well absorbed in the gastrointestinal tract (GIT) and is rapidly and almost completely converted to acyclovir and valine. Bioavailability of acyclovir when taking 1 g of valacyclovir is 54% and is not reduced by simultaneous food intake.

The maximum concentration of acyclovir after a single administration of 250 mg – 1 g of valacyclovir averages 15-25 µmol/L and is reached 1.6-2.1 hours after administration; after 3 hours valacyclovir in plasma is not determined. Valacyclovir’s binding to plasma proteins is 13-18%. Half-life of acyclovir after single and repeated use is about 3 hours.

Valacyclovir is excreted by the kidneys, mainly as acyclovir and its metabolite 9carboxymethoxymethylguanine‑. Acyclovir is widely distributed in tissues and body fluids, including brain, kidney, lung, liver, aqueous humor, tear fluid, intestine, muscle, spleen, uterus, vaginal mucosa and secretion, semen, amniotic fluid, cerebrospinal fluid (CSF) (50% of concentration in plasma), herpes vesicle fluid. The highest concentrations are produced in the kidneys, liver, and intestine. Passes through the placenta and into breast milk.

Indications

The drug is used for:

In adults:

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

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

Pharmacological effect

Pharmacodynamics

Valaciclovir:(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 viral replication. In the human body, valacyclovir is converted to acyclovir and valine.

Acyclovir in vitro 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 into active acyclovir triphosphate, which competitively inhibits the synthesis of viral DNA. The first stage of phosphorylation requires the activity of a virus-specific enzyme. For herpes simplex virus, Varicella zoster virus and Epstein-Barr virus, this is a viral thymidine kinase, present only in cells infected with the virus. During cytomegalovirus infection, phosphorylation of acyclovir is mediated by the phosphotransferase gene product UL97.

Pharmacokinetics

After oral administration, valacyclovir is well absorbed from the gastrointestinal tract (GIT), quickly and almost completely converted to acyclovir and valine. The bioavailability of acyclovir when taking 1 g of valacyclovir 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 valacyclovir averages 15-25 µmol/l and is achieved 1.6-2.1 hours after administration; after 3 hours, valacyclovir is not detected in the blood plasma. 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, vaginal mucosa and secretions, sperm, amniotic fluid, cerebrospinal fluid (CSF) (50% of plasma concentrations), herpetic vesicle fluid. The highest concentrations are created in the kidneys, liver and intestines. Penetrates through the placenta and into breast milk.

Special instructions

Hydration. Elderly patients and persons with dehydration during treatment with valacyclovir need to increase the amount of fluid consumed. In the absence of severe renal dysfunction, no dosage adjustment is required.

Use for impaired renal function and in elderly patients. Valacyclovir is excreted through the kidneys; therefore, elderly patients with a risk of decreased 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 are subject to careful monitoring.

Reducing 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.

Breastfeeding period. It is recommended to prescribe valacyclovir with caution to women during breastfeeding.

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

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

Active ingredient

Valaciclovir

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 (E132) 0.3 mg,

povidone (K 30) 18 mg,

povidone (K 90D) 2 mg,

magnesium stearate 7 mg,

purified water q.s.*

Film casing:

dye Opadry02С50740 blue 21 mg, purified water q.s.*
Composition of Opadry 02C50740 blue dye: 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, indigo carmine dye (E132) 0.42 mg, polysorbate 80 (E433) 0.42 mg

Pregnancy

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

Reported data on pregnancy outcomes 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 with the general population. Since the registry included a small number of women who took valacyclovir during pregnancy, reliable and definite conclusions about the safety of valacyclovir during pregnancy cannot be made.

Acyclovir, the main metabolite of valacyclovir, is excreted in breast milk. After oral administration of valacyclovir 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 plasma. The ratio of the area under the concentration-time curve (AUC) in the blood plasma of acyclovir found 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 concentration of acyclovir in breast milk was 2.24 μg/ml (9.95 μg/M). When the mother takes valacyclovir orally at a dose of 500 mg 2 times a day. the child will be exposed to the same effects of acyclovir as if 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 from blood plasma. Valaciclovir unchanged was not detected in maternal plasma, breast milk or child urine.

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

In experimental studies, valacyclovir did not have a teratogenic effect in rats and rabbits. Subcutaneous (SC) administration of acyclovir did not produce teratogenic effects in rats and rabbits in conventional teratogenicity tests. In additional studies on rats, fetal developmental disorders were identified with subcutaneous administration 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.

When administered orally, valacyclovir did not cause fertility problems in male or 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. Liver/renal failure, old age, hypohydration, simultaneous 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 “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.

From the immune system: very rarely – 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 in most cases reversible and are noted mainly in patients with renal failure or other risk factors. In patients after organ transplantation receiving valacyclovir for the prevention of cytomegalovirus infection in high doses (8 g per day), neurological reactions occur more often than in those receiving lower doses.

From the respiratory system and thoracic organs: infrequently – shortness of breath.

From 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 photosensitivity phenomena; rarely – itching; very rarely – urticaria, angioedema.

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

Other: There are reports of renal failure, microangiopathy, hemolytic anemia and thrombocytopenia (sometimes in combination) in severely immunocompromised patients, especially in patients in the later stages of HIV infection who have received high doses (8 g per day) of valacyclovir for a long time.

Interaction

Acyclovir is excreted predominantly unchanged in the urine by active tubular secretion. Any drugs prescribed concomitantly with valacyclovir and having this elimination mechanism 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, there is no need for dose adjustment due to the broad 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 drugs that compete with sacyclovir for elimination routes, since this may lead to increased plasma levels of one or both drugs and their metabolites. When taken simultaneously with mycophenolate mofetil, the concentration of acyclovir and the inactive metabolite of mycophenolate mofetil increases in the blood plasma. Caution should also be exercised when simultaneously prescribing valacyclovir in high doses and other drugs that affect renal function (for example, cyclosporine, tacrolimus).

Overdose

Symptoms
The occurrence of acute renal failure and neurological symptoms, including confusion, hallucinations, agitation, loss of consciousness and coma in patients with an overdose of valacyclovir, 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 of the drug.

Treatment
Patients should be closely monitored for timely diagnosis of toxic manifestations. Hemodialysis significantly accelerates the elimination of acyclovir from the blood and can be considered the optimal treatment method in case of symptomatic overdose.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Manufacturer

Sun Pharmaceutical Industries Ltd, India