Vatsireks - instructions for use, doses, side effects, contraindications

Excipients: lactose (milk sugar) 80 mg, silicon dioxide colloid (aerosil) 15 mg, maltodeketrin 12 mg, potato starch 37.8 mg, hydroxypropyl methylcellulose (hypromellose) 16 mg, sodium lauryl sulfate 3.2 mg, crospovidone CL) 52 mg, magnesium stearate 8 mg;

excipients for the shell: hydroxypropylmethylcellulose (hypromellose) 16.41 mg, polyethylene glycol 6000 (macrogol 6000) 4.83 mg, titanium dioxide 2.76 mg.

Description:

Tablets covered with a film coat of white or almost white color, biconvex, oblong with rounded ends, with a risk. In the cross section, the inner layer 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:

Valacyclovir is an antiviral agent, is a L-valine new ester of acyclovir. Acyclovir is an analogue of a purine nucleoside (guanine).

In the human body valaciclovir quickly and completely turns into acyclovir and valine under the influence of the enzyme valacyclovirhydrolase. Acyclovir possesses in vitro specific inhibitory activity against viruses: herpes simplex virus (HSV), type 1 and type 2, varicella zoster virus and herpes zoster (VZV - varicella zoster virus, Varicella zoster virus), cytomegalovirus (CMV), the Epstein-Barr virus (EBV), the human herpesvirus type 6 type. Acyclovir inhibits the synthesis of viral DNA immediately after phosphorylation and conversion into active form of acyclovir triphosphate.The first stage of phosphorylation requires the activity of a virus specific enzymes. For HSV, VZV, VEB, this enzyme is viral thymidine kinase, which is present in the cells infected with the virus. Partial selectivity of phosphorylation is maintained in the cytomegalovirus and is mediated through the product of the phosphotransferase gene UL 97. Activation of acyclovir with a specific viral enzyme to a great extent explains its selectivity.

The process of phosphorylation of acyclovir (conversion from mono- to triphosphate) is completed by cellular kinases. Acyclovir the nucleoside triphosphate is inserted into the viral DNA, which leads to an obligate rupture of the chain, the cessation of DNA synthesis and, consequently, to the blocking of viral replication.

In patients with preserved immunity, HSV and VZV with a reduced sensitivity to valaciclovir are extremely rare, but can sometimes be found in patients with severe immunity disorders, for example, in patients with bone marrow transplant, in chemotherapy for malignant neoplasms and in HIV-infected patients .

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

Pharmacokinetics:

Suction

After oral administration valaciclovir well absorbed from the gastrointestinal tract. With the participation of the liver enzyme valaciclovirhydrolase quickly and almost completely turns into acyclovir and valine. After a single dose of valacyclovir in a dose of 250-2000 mg, the average maximum concentration of acyclovir in plasma in healthy volunteers with normal renal function is 10-37 μmol (2.2-8.3 μg / ml), and the median time to reach this concentration of 1- 2 hours. When taking valaciclovir in a dose of 1000 mg, the bioavailability of acyclovir is 54% and does not depend on the intake of food. The maximum concentration of valacyclovir in plasma is only 4% of the concentration of acyclovir, the average time to reach the maximum concentration of valacyclovir in the blood plasma is 30-100 minutes after the dose, the limit of quantitative determination of valaciclovir in plasma is reached after 3 hours or earlier. Valaciclovir and acyclovir have similar pharmacokinetic parameters after oral administration.

Distribution

The degree of binding of valacyclovir to blood plasma proteins is low - 15%.

Excretion

In patients with normal renal function, the half-life of acyclovir from blood plasma after taking valacyclovir is about 3 hours, and in patients with the final stage of renal failure, the average half-life is about 14 hours. Valaciclovir is excreted from the body by the kidneys mainly in the form of acyclovir (more than 80% of the dose) and the metabolite of acyclovir 9-carboxymethoxymethylguanine, in an unchanged form, less than 1% of the drug is eliminated.

Special patient groups

The pharmacokinetics of valaciclovir and acyclovir are largely unchanged in patients infected with HSV and BWV viruses.

In late pregnancy, the daily indicator of the area under the "concentration-time" curve (AUC) in the equilibrium state after taking 1000 mg of valaciclovir was more approximately 2-fold than that with acyclovir at a dose of 1200 mg per day.

In HIV-infected patients, the pharmacokinetic parameters of acyclovir after ingestion of valacyclovir in a dose of 1000 mg or 2000 mg are comparable to those observed in healthy volunteers.

In transplant recipients of organs receiving valaciclovir in a dose of 2000 mg 4 times a day, the maximum concentration of acyclovir was comparable or exceeded the concentration observed in healthy volunteers after taking the same doses, while the daily area under the pharmacokinetic curve was significantly higher.

Indications:

Adults:

- Treatment of herpes zoster (Herpes zoster) (the drug contributes to the relief of pain syndrome, reduces its duration and the percentage of patients with pain caused by herpes zoster, including acute and postherpetic neuralgia).

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

- Prevention (suppression) of recurrences of infections of the skin and mucous membranes caused by HSV, including genital herpes.

- Prophylaxis of transmission of genital herpes to a healthy partner when taken as a suppressive therapy in conjunction with safe sex.

Adults and adolescents aged 12 years and over:

- Prevention of cytomegalovirus (CMV) infection,as well as reactions of acute graft rejection (in patients with kidney transplants), opportunistic infections and other herpesvirus infections (HSV, VZV) after organ transplantation.

Contraindications:

- Hypersensitivity to valaciclovir, acyclovir and any other component of the drug;

- HIV infection with content Cd4+ lymphocytes less than 100 / μl;

- dUp to 12 years of age in the prevention of cytomegalovirus (CMV) infection after transplantation;

- dUnder-18 for all other indications (due to insufficient data on clinical studies for this age group);

- Mr.lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Carefully:

Hepatic / kidney failure; clinically expressed forms of HIV infection in patients; simultaneous administration of nephrotoxic drugs; pregnancy; the period of breastfeeding; elderly age; hypohydration.

Pregnancy and lactation:

Pregnancy

There are limited data on the use of valacyclovir in pregnancy. The application is possible only in those cases,when the potential benefit to the mother exceeds the possible risk to the fetus.

Data of registration records on the outcome of pregnancy in women who took valaciclovir or other preparations containing acyclovir (acyclovir is an active metabolite of Vatsireks^®), did not reveal an increase in the number of birth defects in their children compared to the general population. Because the register includes a small number of women who valaciclovir during pregnancy, it is impossible to make reliable and definite conclusions about the safety of valacyclovir in pregnancy.

Breastfeeding period

Acyclovir, the main metabolite of valacyclovir, is excreted in breast milk. After administration of valaciclovir in a dose of 500 mg, the maximum concentration of acyclovir (C_mOh) in breast milk in 0,5-2,3 times (an average of 1,4 times) exceeded the corresponding concentrations of acyclovir in the blood plasma of the mother. The average concentration of acyclovir in breast milk was 2.24 μg / ml (9.95 μmol / L). When taking a valacyclovir mother at a dose of 500 mg twice a day, the child will undergo the same effect of acyclovir as if taking it inside at a dose of about 0.61 mg / kg / day. The half-life of acyclovir from breast milk is the same as from plasma. Valaciclovir in unmodified form was not determined in the plasma of the mother, breast milk or urine of the child. The drug Vatsireks® should be administered with caution to women during breastfeeding.

Dosing and Administration:

Inside, regardless of food intake, the tablets should be washed down with water.

Treatment of herpes zoster (Herpes zoster)

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

Treatment of infections caused by HSV

Adults: The recommended dose for therapy of the episode is 500 mg 2 times a day for 5 days.

In more severe cases of debility of the disease, treatment should be started as soon as possible, and its duration should be increased from 5 to 10 days. In case of relapse, treatment should last 3 or 5 days. In cases of recurrence of HSV, the administration of Vacirex® in the prodromal period is ideal, or immediately after the appearance of the first symptoms of the disease.

As an alternative for the treatment of labial herpes, effective administration of the drug VACIREX® in a dose of 2 g twice daily. The second dose should be taken after approximately 12 hours (but not earlier than 6 hours) after taking the first dose.When using this mode of dosing, the duration of treatment is 1 day. Therapy should be started when the earliest symptoms of the labial herpes (the network tingling, itching, burning) occur.

Prevention (suppression) of recurrences of infections caused by HSV

Adults: in patients with preserved immunity, the recommended dose is 500 mg once a day.

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

Prophylaxis of transmission of genital herpes to a healthy partner

Infected adults with preserved immunity and with number of exacerbations up to 9 times a year valaciclovir should be taken at 500 mg once a day for a year or more, every day.

Data on the prevention of infection in other patient populations are not available.

Prevention of CMV infection after transplantation

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

Specials groups patients

Patients with impaired renal function

Treatment of herpes zoster and infections, caused by HSV, prevention (suppression) of recurrent infections, caused by HSV \ prophylaxis of transmission of genital herpes healthy y partner.

Such patients need to maintain adequate hydration. The dose of Vaccarex® is recommended to be reduced in patients with a significant decrease in renal function (see doses in renal failure in the table below).

The experience of using VACIREX® in children with creatinine clearance values of less than 50 ml / mii / 1.73 m² no.

Indications	Clearance creatinine, ml / min	The dose of Vaccarex®
Shingles (Herpes zoster)	15-30 less than 15	1 g 2 times a day 1 g 1 once a day
Treatment of infection caused by HSV (according to the scheme 500 mg twice a day)	less than 15	500 mg once a day
Treatment of labial herpes (according to the 2000 mg schedule in 2 divided doses for 1 day)	31-49 15-30 less than 15	1 g twice for 1 day 500 mg twice for 1 the day 500 mg once
Prevention (suppression) of recurrences of infections caused by HSV: - Patients with preserved immunity - Patients with reduced immunity	less than 15 less than 15	250 mg once a day 500 mg once a day
Reducing the risk of transmission of genital herpes	less than 15	250 mg once a day

Patients on hemodialysis are recommended to use Vatsireks® immediately after the end of the hemodialysis session at the same dose as patients with creatinine clearance less than 15 ml / min.

Prevention of CMV infections after transplantation

The mode of prescribing Vaccarex® in patients with impaired renal function should be established in accordance with the table below.

Creatinine clearance, ml / min	Valacyclovir dose
75 and more	2 g 4 times a day
from 50 to 74 inclusive	1.5 gm 4 times per day
from 25 to 49 inclusive	1,5 g 3 times a day
from 10 to 24 inclusive	1.5 g 2 times a day
less than 10 or dialysis	1.5 g once a day

In patients on hemodialysis, the drug Vatsireks® should be prescribed after the end of the hemodialysis session.

It is often necessary to determine the creatinine clearance, especially during periods when the kidney function changes rapidly, for example, immediately after transplantation or engraftment, while the dose of VACIREX® is adjusted in accordance with the creatinine clearance values.

Patients with impaired hepatic function

In adult patients with mild or moderate liver dysfunction, with a viable synthetic dose adjustment function, VACIREX® is not required.Pharmacokinetic data in patients with severe liver impairment (decompensated cirrhosis) with a violation of the synthetic function of the liver and the presence of portocaval anastomoses also do not indicate the need to adjust the dose of the drug VACIREX, but the experience of its clinical use in this pathology is limited.

Children under the age of 12 years

There is no data on the use of Vacirex ® in children.

Elderly patients

Dose adjustment is not required, except for a significant impairment of kidney function. It is necessary to maintain an adequate water-electrolyte balance.

Side effects:

Undesirable reactions are listed below in accordance with the classification of the main systems and organs and the frequency of occurrence.

Classification of WHO frequency of development of side effects:

Often:	≥1 / 10 appointments (> 10%)
often:	from ≥1 / 100 to <1/10 of prescriptions (≥1% and <10%)
infrequently:	from ≥1 / 1000 to <1/100 of prescriptions (≥0.1% and <1%)
rarely:	from≥1 / 10,000 to <1/1000 appointments (≥0.01% and <0.1%)
rarely:	<1/10000 appointments (0.01%)
frequency is unknown:	according to available data to establish the frequency of occurrence is not possible.

Impaired nervous system:

Often: headache.

Rarely: disturbance and confusion, loss of consciousness.

Disorders from the gastrointestinal tract:

Often: nausea.

Post-marketing research data

Violations of the blood and lymphatic system

Very rarely: leukopenia, thrombocytopenia. In general, leukopenia was noted in patients with reduced immunity.

Immune system disorders

Very rarely: anaphylaxis.

Mental disorders and disorders of the nervous system and psyche:

Rarely: dizziness, confusion, hallucinations, depression of consciousness, reduction of mental abilities.

Very rarely: agitation, psychotic symptoms, agitation, tremor, ataxia, dysarthria, convulsions, encephalopathy, coma.

The symptoms listed above are mostly reversible and are usually observed in patients with impaired renal function or against a background of other predisposing conditions.

In adult patients with a transplanted organ who receive high doses of valaciclovir (8 g / day) for the prevention of CMV infection, neurologic reactions develop more often than with lower doses.

Disturbances from the respiratory system, chest and mediastinal organs

Infrequent: shortness of breath.

Disorders from the gastrointestinal tract

Rarely: abdominal discomfort, vomiting, diarrhea, abdominal pain.

Disturbances from the liver and bile ducts

Very rare: reversible disturbances of liver function tests, which are sometimes regarded as manifestations of hepatitis.

Disturbances from the skin and subcutaneous tissues

Infrequent: rashes, including photosensitivity.

Rarely: itching.

Very rarely: urticaria, rash, angioedema.

Disorders from the kidneys and urinary tract

Rarely: impaired renal function.

Very rarely, acute renal failure, renal colic (may be associated with impaired renal function).

In addition, precipitation of acyclovir crystals is observed in the lumen of the renal tubules. Adequate drinking regimen should be observed during treatment.

Hematuria (often associated with other disorders of the kidneys).

Other

Edema of the face, increased blood pressure, tachycardia.

In patients with severe impairment of immunity, especially in patients with advanced HIV infection,(8000 mg daily) for a long period of time, renal insufficiency, microangiopathic hemolytic anemia, and thrombocytopenia (sometimes in combination) were observed. Similar complications were observed in patients with the same diseases, but not receiving valaciclovir.

Side effect, revealed as a result of spontaneous messages

Disorders from the nervous system and psyche: aggressive behavior, mania.

Disturbances on the part of the organ of sight: impaired vision.

Violations of the blood and lymphatic system: thrombocytopenia, aplastic anemia, leukocytoclastic vasculitis, thrombocytopenic purpura / hemolytic uremic syndrome.

Disturbances from the skin and subcutaneous tissues: erythema, alopecia.

Overdose:

Symptoms: acute renal failure and neurological disorders, including confusion, hallucinations, agitation, depression and coma, as well as nausea and vomiting were observed in patients who received doses of valaciclovir exceeding recommended. Similar conditions were more frequent in patients with impaired renal function and in elderly patients who received repeated,exceeding the recommended dose of valacyclovir due to non-compliance with the dosing regimen.

Treatment: patients should be under close medical supervision. Hemodialysis greatly contributes to the elimination of acyclovir from the blood and can be considered a method of choice in managing patients with an overdose of valaciclovir.

Interaction:

Clinically significant interactions are not established. Acyclovir is excreted by the kidneys mainly in the unmodified form, through active renal secretion. Combined use of drugs with this removal mechanism can lead to an increase in the concentration of acyclovir in the blood plasma. After the appointment of 1 g valacyclovir, cimetidine and probenecid, which are derived in the same way as valaciclovirincrease AUC acyclovir and reduce its renal clearance. However, in view of the wide therapeutic index of acyclovir, the dose adjustment of Vatsireks^® in this case is not required.

Care should be taken when using valaciclovir simultaneously at higher doses (4 g per day or more) and drugs that compete with acyclovir for the pathway of elimination,hack as there is a potential threat of an increase in plasma concentrations of one or both drugs or their metabolites. An increase was noted AUC acyclovir and an inactive metabolite of mycophenolate mofetil, an immunosuppressive drug used in transplantation, while simultaneously using these drugs.

Care should also be taken (to observe changes in kidney function) when valacyclovir is combined at higher doses (4 g per day or more) with drugs that affect other kidney functions (for example, ciclosporin, tacrolimus). The simultaneous use of valacyclovir with nephrotoxic drugs, including aminoglycosides, organic compounds of the plugin, iodinated 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.

When valacyclovir interacts with antacids, cimetidine and / or probenecid, digoxin, thiazide diuretics in patients with normal renal function, dose adjustment is not required.

Special instructions:

Patients with a risk of dehydration, especially elderly patients, during treatment with valaciclovir must ensure adequate fluid replenishment. Because the acyclovir is excreted by the kidneys, the dose of Vaccikss^® should be adjusted depending on the degree of impairment of renal function. In patients with renal insufficiency, there is an increased risk of developing neurological complications, such patients need to be closely monitored. As a rule, these reactions, in general, are reversible after drug discontinuation.

There are no data on the use of Vatsirex® at high doses (4 g per day or more) in patients with liver disease, so high doses of Vatsireks^® they should be administered with caution.

Special studies to study the effects of valaciclovir in liver transplant were not performed. However, it has been shown that prophylactic intravenous administration of acyclovir in high doses reduces the manifestations of CMV infection.

Suppressive therapy with Vatsireks^®reduces the risk of transmission of genital herpes, but does not exclude it completely and does not lead to complete cure.Therapy with Vatsireks® is recommended in combination with safe sex.

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

It is necessary to consider the clinical state of the patient and profile of adverse reactions of valaciclovir at assessment of a patient's ability to drive or move vehicles.

Form release / dosage:Tablets, film-coated, 500 mg.

Packaging:

For 6, 7, 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 1, 2, 3, 4, 5, 6, 7 contour squares, together with instructions for use, are placed in a pack of cardboard.

Storage conditions:

In a dry, dark place, at a temperature of no higher than 25 FROM.

Keep out of the reach of children.

Shelf life:

3 gramsOh yeah.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009166/09

Date of registration:13.11.2009 / 19.02.2015

Expiration Date:Unlimited

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Information update date: & nbsp24.01.2017

Illustrated instructions

Instructions

Vacrex (Vacirex)