Valcycon, pills 500mg, 42pcs

Composition

1 film-coated tablet contains:

Active ingredient:

valacyclovir hydrochloride – 556.00 mg (based on valacyclovir 500.00 mg);

excipients:

microcrystalline cellulose-95.00 mg,

hyprolose (hydroxypropylcellulose) – 14.00 mg,

crospovidone-28.00 mg,

magnesium stearate-7.00 mg;

film shell:

hypromellose — 10,5 mg;

hyprolose (hydroxypropylcellulose) – 4.07 mg;

talc — 4.12 mg;

titanium dioxide-2.31 mg or dry mixture for film coating white (hypromellose-50%, hydroxypropylcellulose-19.4%, talc-19.6%, titanium dioxide-11%) — 21 mg

Pharmacological action

Pharmacodynamics

Valacyclovir is a nucleoside inhibitor of herpes virus DNA polymerase. Blocks viral DNA synthesis and virus replication. In humans, valacyclovir is completely converted to acyclovir and L-valine. Acyclovir in vitro has specific inhibitory activity against herpes simplex viruses (HSV, Herpes simplex) types 1,2, varicella zoster virus (VZV-Varicella zoster virus, Varicella zoster), CMV, Epstein-Barr virus (EBV) and human herpes virus type 6.

Acyclovir inhibits the synthesis of viral DNA immediately after phosphorylation and conversion to the active form-acyclovir triphosphate. The first stage of phosphorylation occurs with the participation of virus-specific enzymes.

For HSV, VZV, and EBV viruses, such an enzyme is viral thymidine kinase, which is present in virus-affected cells. Partial phosphorylation selectivity is preserved in CMV and is mediated through the phosphotransferase gene product UL 97. Activation of acyclovir by a specific viral enzyme largely explains its selectivity.

The process of phosphorylation of acyclovir (conversion from mono – to triphosphate) is completed by cellular kinases. Acyclovir triphosphate competitively inhibits viral DNA polymerase and, being an analog of a nucleoside, is embedded in viral DNA, which leads to an obligate chain break, stopping DNA synthesis and, consequently, blocking viral replication.

In immunocompromised patients, HSV and VZV viruses with reduced sensitivity to valacyclovir are extremely rare (less than 0.1%), but can sometimes be detected in patients with severe immune disorders, such as those with a bone marrow transplant, those receiving chemotherapy for malignancies, and those infected with HIV.

Resistance is caused by a deficiency of thymidine kinase of the virus, which leads to excessive spread of the virus in the host. Sometimes a decrease in sensitivity to acyclovir is due to the appearance of virus strains with a violation of the structure of viral thymidine kinase or DNA polymerase. The virulence of these varieties of the virus is similar to that of its wild strain.

Pharmacokinetics

Suction. After oral use, valacyclovir is well absorbed from the gastrointestinal tract, quickly and almost completely converted to acyclovir and valine. This transformation is catalyzed by the liver enzyme valacyclovir hydrolase. After a single dose of 250-2000 mg of valacyclovir, the average Cmax of acyclovir in blood plasma in healthy volunteers with normal renal function is on average 10-37 mmol/l (2.2-8.3 mcg / ml), and the average Tmax is 1-2 hours.

When taking valacyclovir at a dose of 1000 mg or more, the bioavailability of acyclovir is 54% and does not depend on the intake of food. Cmax of valacyclovir in blood plasma is only 4% of the concentration of acyclovir, Tmax on average — 30-100 minutes after taking the drug; after 3 hours, the Cmax level remains the same or decreases. Valacyclovir and acyclovir have similar pharmacokinetic parameters after oral use.

Distribution. Binding to proteins of valacyclovir — 13-18%, acyclovir-9-33%. Acyclovir is well distributed in tissues and body fluids, including the brain, kidneys, lungs, liver, watery moisture, tear fluid, intestines, muscles, spleen, uterus, mucous membrane and vaginal secretions, semen, amniotic fluid, cerebrospinal fluid (50% of plasma concentration), herpetic vesicle fluid. The highest concentrations are created in the kidneys, liver, and intestines. Penetrates through the placenta and into breast milk.

Output. Valacyclovir is excreted in the urine, mainly in the form of acyclovir (more than 30% of the dose) and its metabolite 9-carboxymethoxymethylguanine, and less than 1% of the drug is excreted unchanged. T1 / 2 of valacyclovir is less than 30 minutes, acyclovir-2.5–3.3 hours. In elderly patients (65-83 years), the T1/2 of acyclovir is 3.3-3.7 hours, and in patients with end — stage renal failure-approximately 14 hours.

The pharmacokinetics of valacyclovir and acyclovir are largely unaffected in patients infected with HSV and VZV viruses.

In HIV-infected patients, the pharmacokinetic parameters of acyclovir after oral use of valacyclovir at doses of 1000 and 2000 mg are comparable to those observed in healthy volunteers.

In organ transplant recipients receiving valacyclovir 2000 mg 4 times a day, the Cmax of acyclovir was equal to or higher than that of healthy volunteers receiving the same dose of the drug, and the daily AUC values were significantly higher.

In late pregnancy, the stable daily AUC after taking 1000 mg of valacyclovir was approximately 2 times higher than that when taking acyclovir at a dose of 1200 mg/day.

Indications

Adults:

• the treatment of herpes zoster (Herpes zoster) (the drug helps to eliminate pain, reduce its duration and the percentage of patients with pain caused by shingles, including acute and post-herpetic neuralgia);
• treatment of infections of the skin and mucous membranes caused by Herpes simplex virus 1,2 type including first diagnosed and recurrent genital herpes (Herpes genitalis), and labially herpes (Herpes labialis);
• prophylaxis (suppression) of recurrent infections of the skin and mucous membranes caused by Herpes simplex virus 1,2 kind, including genital herpes;
• prevention of transmission of genital herpes to a healthy partner for the use of the drug as a suppressive therapy in combination with safe sex;

Adults and children aged 12 years and older: prevention of cytomegalovirus (CMV) infection, as well as acute graft rejection reactions (in patients with kidney transplants), opportunistic infections and other herpesvirus infections (HSV, VZV) after organ transplantation.

Use during pregnancy and lactation

There are limited data on the use of valacyclovir in pregnancy.

Valacyclovir is only used when the potential benefit to the mother outweighs the potential risk to the fetus. Registered data on pregnancy outcome in women taking valacyclovir or acyclovir (the 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 valacyclovir during pregnancy, reliable and definite conclusions about the safety of using valacyclovir during pregnancy cannot be made.

Acyclovir, the main metabolite of valacyclovir, is excreted in breast milk. After taking valacyclovir orally 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 blood plasma.

The mean acyclovir concentration in breast milk was 2.24 mcg / ml (9.95 mcmol / L). When the mother takes valacyclovir orally at a dose of 500 mg 2 times / day, the child will be exposed to the same effect of acyclovir as when taking acyclovir orally at a dose of about 0.61 mg / kg / day.

Contraindications

• hypersensitivity to valacyclovir, acyclovir and / or any other component of the drug;
• HIV infection with a CD4+ lymphocyte count of less than 100 in 1 µl;
• children (up to 12 years of age in the prevention of CMV infection after transplantation, up to 18 years – for other indications).

With caution: hepatic / renal insufficiency; elderly age; hypohydration; concomitant use of nephrotoxic drugs; pregnancy; lactation; clinically expressed forms of HIV infection.

Side effects

From the central nervous system: headache, dizziness, psychotic symptoms, restlessness, decreased mental abilities, ataxia, coma, confusion or depression of consciousness, dysarthria, encephalopathy, mania, hallucinations, convulsions, tremor.

These reactions are reversible and usually occur in patients with impaired renal function or other predisposing conditions. In organ transplant patients receiving high-dose valacyclovir (8 g / day) to prevent cytomegalovirus infection, neurological reactions develop more frequently than when taken at lower doses.

Respiratory system disorders: dyspnoea.

From the digestive system: nausea, abdominal discomfort, vomiting, diarrhea, reversible violations of functional liver tests (increased activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase), which are sometimes regarded as manifestations of hepatitis.

From the hematopoietic system: leukopenia (mainly observed in patients with reduced immunity), thrombocytopenia, anemia, thrombotic thrombocytopenic purpura. From the skin: erythema multiforme, rashes, photosensitization, alopecia.

Allergic reactions:pruritus, urticaria, angioedema, anaphylaxis. From the urinary system: pain in the projection of the kidneys, impaired renal function, including acute renal failure, renal colic. Renal colic may be associated with impaired renal function.

From the side of the senses: visual impairment.

Laboratory parameters: decreased hemoglobin content, hypercreatininemia.

Other: dysmenorrhea, nasopharyngitis, respiratory tract infections, increased blood pressure, tachycardia, fatigue; patients with severe immune disorders, especially in adult patients with advanced HIV infection, receiving valacyclovir 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 adverse reactions have been reported in patients with the same medical conditions but not treated with valacyclovir.

Interaction

Cimetidine and tubular secretion blockers reduce the effect (reduce the rate, but not the completeness of conversion to acyclovir). Correction of the dosage regimen in individuals with normal creatinine clearance is not required.

Nephrotoxic medications increase the risk of developing impaired renal function. Caution should be exercised (to monitor changes in renal function) when combining Valcycone in higher doses (4 g per day or more) with drugs that affect other renal functions (for example: cyclosporine, tacrolimus).

Acyclovir is mainly excreted unchanged by the kidneys through active renal secretion. The combined use of drugs with this elimination mechanism may lead to an increase in the concentration of acyclovir in blood plasma.

After prescribing Valcycone at a dose of 1000 mg, cimetidine and probenecid, which are eliminated in the same way as valacyclovir, increase the AUC of acyclovir and thus reduce its renal clearance. Due to the broad therapeutic index of acyclovir, dose adjustment of Valcycone is not required in this case.

Caution should be exercised in the case of concomitant use of valacyclovir in higher doses (4 g per day or higher) and drugs that compete with acyclovir for the elimination pathway, since there is a potential threat of increased plasma levels of one or both drugs or their metabolites.

There was an increase in the AUC of acyclovir and the inactive metabolite mycophenolate mofetil with simultaneous use of these drugs. The pharmacokinetics of valacyclovir do not change when administered concomitantly with digoxin, aluminum / magnesium-containing antacids, and thiazide diuretics.

How to take, course of use and dosage

Valcycon is taken orally, regardless of food intake, washed down with water. Treatment of shingles (Herpes zoster)Adults:The recommended dose is 1000 mg 3 times a day for 7 days.

Treatment of HSV infections

Adults:The recommended dose for treating an episode is 500 mg twice daily for 5 days. In more severe cases, the onset of the disease should begin as early as possible, and its duration can be increased from 5 to 10 days. In case of relapses, treatment should continue for 3 or 5 days. When HSV relapses, valacyclovir is considered ideal in the prodromal period or immediately after the first symptoms of the disease appear.

As an alternative for the treatment of labial herpes, valacyclovir is effective at a dose of 2 g twice a day. The second dose should be taken approximately 12 hours (but not earlier than 6 hours) after the first dose. When using this dosage regimen, the duration of treatment is 1 day. Therapy should be initiated when the earliest symptoms of labial herpes appear (i. e. tingling, itching, burning).

Prevention (suppression) of recurrent HSV infections

Adults:In immunocompromised patients, the recommended dose is 500 mg once daily. In patients with immunodeficiency, the recommended dose is 500 mg 2 times a day.

Prevention of transmission of genital herpes to a healthy partnerinfected immunocompetent individuals with relapses no more than 9 times a year the recommended dose of valacyclovir is 500 mg 1 time a day for a year or more every day. There are no data on the prevention of infection in other populations of patients.

Prevention of cytomegalovirus (CMV) infection after transplantation

Adults and adolescents aged 12 years and older:The recommended dose is 2 g 4 times a day, prescribed as early as possible after transplantation. The dose should be reduced depending on creatinine clearance. The duration of treatment is 90 days, but in high-risk patients, the course of treatment can be extended.

Overdose

Symptoms: An overdose of valacyclovir may cause acute renal failure and neurological symptoms, including confusion, hallucinations, agitation, depression of consciousness and coma, as well as nausea and vomiting. To prevent overdose, caution should be exercised when using the drug.

Many cases of overdose were associated with the use of the drug for the treatment of patients with impaired renal function and elderly patients, due to non-compliance with the dosage regimen (re-received doses of valacyclovir exceeding the recommended ones).

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

Special instructions

In patients at risk of dehydration, especially in the elderly, adequate fluid replenishment should be provided during treatment.

Since acyclovir is excreted by the kidneys, the dose of Valcycone should be adjusted depending on the degree of impaired renal function. Patients with renal insufficiency have an increased risk of developing neurological complications, and such patients should be closely monitored. As a rule, these reactions are reversible and disappear after discontinuation of the drug.

In patients with chronic renal failure (CRF), it is recommended to frequently determine creatinine clearance, especially when renal function changes rapidly (in particular, immediately after transplantation or graft engraftment), and the dose of valacyclovir is adjusted according to creatinine clearance indicators.

There are no data on the use of valacyclovir in high doses (4 g or more per day) in patients with liver disease, so high doses of Valcycone should be prescribed with caution.

Suppressive therapy with valacyclovir reduces the risk of transmission of genital herpes, but does not eliminate the risk of infection and does not lead to a complete cure. Valcycone therapy is recommended in combination with safe sex.

Taking 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 fatal outcome.

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

Effects on vehicle management and mechanismmi Net of data on the effect of valacyclovir, used in therapeutic doses, on the ability to drive vehicles and mechanisms. However, when evaluating the patient’s ability to drive a car or move machinery, it is necessary to take into account that side effects from the central nervous system may occur, so caution should be exercised.

Form of production

Film-coated tablets

Storage conditions

In a dark place, at a temperature not exceeding 25 °C

Shelf life

2 years

Active ingredient

Valacyclovir

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by a doctor, For Children over 12 years of age, For adults, For Children as directed by a doctor

Indications

Cold, Herpes, Cytomegalovirus infection