Valacyclovir pills 500mg, 50pcs

Composition

1 film-coated tablet contains:

Composition of the tablet core:

Active ingredient:

valacyclovir hydrochloride – 556.2 mg (based on valacyclovir 500.0 mg).

Auxiliary substances:

microcrystalline cellulose-84.3 mg,

hypromellose-42.0 mg,

crospovidone-7.0 mg,

magnesium stearate-7.0 mg,

colloidal silicon dioxide -3.5 mg.

Composition of the tablet shell:

Opadray II white (33G28435) – 25.0 mg (hypromellose-40.0%, titanium dioxide-25.0%, macrogol 3350-8.0%, lactose monohydrate-21.0%, triacetin-6.0%).

Pharmacological action

Antiviral agent. Pharmacodynamics

Valacyclovir is an antiviral agent, it is an L-valine ester of acyclovir. Acyclovir is an analog of purine nucleoside (guanine). In humans, valacyclovir is rapidly and almost completely converted to acyclovir and L-valine, presumably under the influence of the enzyme valacyclovir hydrolase.

Acyclovir in vitro has a specific inhibitory activity against herpes simplex viruses (HSV) 1,2 types (Herpes simplex 1,2 types), varicella and herpes zoster (RDT – varicella-zoster virus, Varicella zoster virus), cytomegalovirus (CMV), virus Epstein-Barr (EBV) and human herpes virus type 6. Acyclovir inhibits viral DNA synthesis immediately after phosphorylation and conversion to the active form of 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 only in virus-affected cells. Partial phosphorylation selectivity is preserved in cytomegalovirus and is mediated through the phosphotransferase gene product UL97. 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 a nucleoside analog, is incorporated into 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, 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.

Acyclovir resistance is caused by a deficiency in the 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.

Indications

Adults and adolescents aged 12 to 18 years

• treatment of infections of the skin and mucous membranes caused by HSV, including the first identified and recurrent genital herpes (Herpes genitalis), and labially herpes (Herpes labialis);

• prophylaxis (suppression) of recurrent infections of the skin and mucous membranes caused by HSV, including genital herpes, including adults with immunodeficiency;

• prevention of infections caused by cytomegalovirus (CMV), and disease after transplantation organs.

Adult

• treatment of herpes zoster and ophthalmic herpes zoster.

Use during pregnancy and lactation

Pregnancy There are limited data on the use of valacyclovir and insignificant data on the use of acyclovir (the active metabolite of valacyclovir) in pregnancy in women. Registered data on pregnancy outcome in women taking valacyclovir or acyclovir did not show an increase in the number of birth defects in their children compared to the general population. Valacyclovir is only used when the potential benefit to the mother outweighs the potential risk to the fetus. Lactation Acyclovir, the main metabolite of valacyclovir, is excreted in breast milk. After use of valacyclovir at a dose of 500 mg orally, 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 at a dose of 500 mg 2 times a day, the child is exposed to the same effect of acyclovir as when taken orally at a dose of about 0.61 mg / kg / day. The elimination half-life of acyclovir from breast milk is the same as from blood plasma. Valacyclovir was not detected unchanged in the mother’s blood plasma, breast milk, or urine of the child. Valacyclovir should be administered with caution to women who are breast-feeding.

Contraindications

• Hypersensitivity to valacyclovir, acyclovir and any other component of the drug;
• HIV infection when the content of CD4+ lymphocytes is less than 100 in 1 microliter;
• Children under 12 years of age;
• Children under 18 years of age in the treatment of herpes zoster and ophthalmic herpes zoster.

With caution

Renal insufficiency, elderly age, patients at risk of dehydration, concomitant use of nephrotoxic drugs, pregnancy, lactation, clinically expressed forms of HIV infection in patients.

Side effects

Side effect frequency categories: very common (>1/10), common (>>1/100 to >><1/10), infrequent (>1/1000 to <1/10), infrequent (><1/100), rare (>1/10000 to <1/100), rare (><1/1000), very rare (

From the gastrointestinal tract: often-nausea; rarely-abdominal discomfort, vomiting, diarrhea.

From the blood system and hematopoietic organs: very rarely – leukopenia (mainly observed in patients with reduced immunity), thrombocytopenia.

Immune system disorders: rarely-anaphylaxis.

From the nervous system and psyche: often-headache; rarely-dizziness, confusion, hallucinations, depression of consciousness; very rarely-tremor, agitation, ataxia, dysarthria, psychotic symptoms, convulsions, encephalopathy, coma.

The symptoms listed above are mostly reversible and are usually seen in patients with renal insufficiency or other predisposing conditions. In organ transplant patients receiving high-dose valacyclovir (8 g / day) to prevent CMV infection, neurological reactions develop more frequently than when taken at lower doses.

From the respiratory system: infrequently-shortness of breath.

From the liver and biliary tract: very rarely – reversible violations of functional liver tests, which are sometimes regarded as a manifestation of hepatitis.

From the skin and subcutaneous fat: infrequently-rashes, including manifestations of photosensitivity; rarely-pruritus; very rarely-urticaria, angioedema.

From the urinary system: infrequently-hematuria (often associated with other renal disorders); rarely-impaired renal function; very rarely-acute renal failure, renal colic.

Acyclovir crystals were also deposited in the lumen of the renal tubules. During treatment, an adequate drinking regime should be observed.

Cases of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia(sometimes in combination) have been reported in patients with severe immune disorders, especially in adult patients with advanced HIV infection who receive valacyclovir in high doses (8 g/day daily) for a long time. Similar complications were reported in patients with the same underlying and / or comorbidities, but not treated with valacyclovir.

Interaction

No clinically significant interactions have been established.

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

After use of Valacyclovir 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. However, due to the broad therapeutic index of acyclovir, dose adjustment of Valacyclovir is not required in this case.

Caution should be exercised in the case of concomitant use of Valacyclovir in higher doses (4000 mg per day or higher) and drugs that compete with acyclovir for the elimination route, since there is a potential threat of increased plasma concentrations of one or both drugs or their metabolites. There was an increase in the AUC of acyclovir and the inactive metabolite mycophenolate mofetil (an immunosuppressant used after organ transplantation) when taking these drugs simultaneously.

Concomitant use of valacyclovir with nephrotoxic drugs, including aminoglycosides, organic platinum compounds, iodized contrast agent, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus, should be carried out with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function.

How to take it, course of use and dosage

Inside, regardless of food intake, washed down with water.

Treatment of skin and mucosal infections caused by HSV, including first-time and recurrent genital herpes( Herpes genitalis), as well as labial herpes (Herpes labialis)

Immunocompetent adults and adolescents aged 12-18 years

The recommended dose is 500 mg 2 times a day.

In case of relapses, treatment should continue for 3 or 5 days. In the case of primary herpes, which can occur in a more severe form, treatment should begin as early as possible, and its duration should be increased from 5 to 10 days. In case of recurrent HSV, valacyclovir should be prescribed in the prodromal period or immediately after the first symptoms of the disease appear. The use of valacyclovir can prevent the development of a lesion if it is used at the first signs and symptoms of HSV-related relapse.

As an alternative treatment for labial herpes, valacyclovir is effective at a dose of 2000 mg 2 times a day for 1 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 should not exceed 1 day, since exceeding the duration of this course of treatment does not lead to additional clinical benefits.

Therapy should be initiated when the earliest symptoms of labial herpes appear (i. e. tingling, itching, burning).

Prevention (suppression )of recurrent infections of the skin and mucous membranes caused by HSV, including genital herpes, including in adults with immunodeficiency

Immunocompetent adults and adolescents aged 12-18 years

In immunocompetent patients, the recommended dose is 500 mg once a day.

After 6-12 months of treatment, it is necessary to evaluate the effectiveness of therapy.

Adults with immunodeficiency

In adult patients with immunodeficiency, the recommended dose is 500 mg 2 times a day.

After 6-12 months of treatment, it is necessary to evaluate the effectiveness of therapy.

Prevention of CMV infections and diseases after parenchymal organ transplantation

Adults and adolescents aged 12-18 years

The recommended dose is 2000 mg 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 usually 90 days, but in high-risk patients, the course of treatment may be extended.

Treatment of herpes zoster and ophthalmic herpes zoster

Adults

The recommended dose is 1000 mg 3 times a day for 7 days.

Special patient groups

Patients with impaired renal function

The dose of valacyclovir is recommended to be reduced in patients with severe renal impairment (see dosage regimen in Table 2). In such patients, it is necessary to maintain an adequate water-electrolyte balance.

Valacyclovir should be used after hemodialysis in patients undergoing periodic hemodialysis.

Creatinine clearance should be measured frequently, especially when renal function changes rapidly, for example, immediately after transplantation or graft engraftment, and the dose of valacyclovir is adjusted according to creatinine clearance indicators.

There is no experience of using valacyclovir in children with creatinine clearance values less than 50 ml/min/1.73 m2.

Patients with impaired liver function

According to available data on the use of a single dose of valacyclovir 1000 mg, in adult patients with mild to moderate cirrhosis of the liver (with preserved synthetic liver function), dose adjustment of Valacyclovir is not required. Pharmacokinetic data in adult patients with severe hepatic impairment (decompensated cirrhosis), with impaired synthetic liver function and the presence of portocaval anastomoses also do not indicate the need for dose adjustment of Valacyclovir, but clinical experience in these pathologies is limited.

Children under 12 years of age

There are no data on the use of valacyclovir in children under 12 years of age.

Elderly patients

Possible renal impairment in elderly patients should be considered, and the dose of Valacyclovir should be adjusted accordingly (see Table 2). It is necessary to maintain an adequate water-electrolyte balance.

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, the dosage regimen should be observed. 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 (who repeatedly 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 case of overdose.

Special instructions

Hydration

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

Use in patients with renal insufficiency and in elderly patients

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

Use of high doses of valacyclovir in patients with impaired liver function and after liver transplantation

There are no data on the use of valacyclovir in high doses (4000 mg per day and above) in patients with liver disease, so such patients should be prescribed high doses of Valacyclovir with caution. No specific studies have been conducted to investigate the effects of valacyclovir on liver transplantation. However, high-dose prophylactic use of acyclovir has been shown to reduce the appearance of CMV infection and disease.

Use for genital herpes

Patients should refrain from sexual contact in the presence of symptoms, even if antiviral treatment is initiated. 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. Valacyclovir therapy is recommended in combination with reliable means of barrier contraception.

Use in CMV infections

The use of high-dose valacyclovir for the prevention of CMV infection leads to a more frequent occurrence of side effects, including CNS disorders, than when used in lower doses for other indications. It is necessary to carefully monitor the indicators of renal function in such patients with dose adjustment of the drug if necessary.

Influence on the ability to drive vehicles and mechanisms

There are no 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

Store in a dark place at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 2 years. Do not use after the expiration date.

Active ingredient

Valacyclovir

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as prescribed by a doctor, For adults

Indications

Cold, Cytomegalovirus Infection, Herpes