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

Excipients: calcium stearate 7.2 mg, povidone-K90 (kollidone 90 F, plasdon K90) - 10.0 mg, crospovidone (kollidone CL, kollidone CL-M) - 28.8 mg, silicon colloidal dioxide (aerosil) - 3.6 mg, talc - 10.35 mg, microcrystalline cellulose - 103.85 mg;

Shell composition: hypromellose (hydroxypropylmethylcellulose) 15.0 mg, macrogol 4000 (polyethylene oxide 4000, polyethylene glycol 4000) 4.5 mg, titanium dioxide (titanium dioxide) 2.5 mg.

Description:

Tablets are oval in shape, biconvex, covered with a film coat of white or almost white color. On 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:

Mechanism of action

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 almost completely turns into acyclovir and valine is presumably influenced by the enzyme valacyclovirhydrolase.

Acyclovir is a specific inhibitor of herpes viruses with activity in vitro against herpes simplex virus (HSV) of the 1 st and 2 nd types; varicella-zoster virus (VZV) (Varicella zoster virus); cytomegalovirus (CMV), the Epstein-Barr virus (EBV) and the human herpesvirus type 6 type. Acyclovir inhibits the synthesis of viral DNA immediately after phosphorylation and conversion into an active form - acyclovir triphosphate.

The first stage of phosphorylation requires the activity of virus-specific enzymes. For HSV, VZV and VEB, this enzyme is viral thymidine kinase, which is present only in the cells infected with the virus. Partially the selectivity of phosphorylation is maintained in the cytomegalovirus indirectly through the product of the phosphotransferase gene UL97. This need to activate acyclovir with a specific viral enzyme largely explains its selectivity.

The process of phosphorylation of acyclovir (conversion from mono- to triphosphate) is completed by cellular kinases. Acyclovirurt phosphate competitively inhibits the viral DNA polymerase and, being an analogue of the nucleoside, is inserted into the viral DNA, which leads to obligate rupture of the chain, termination of DNA synthesis and, consequently, to blocking the replication of the virus.

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

Based on the results of an extensive study of HSV and VZV strains selected from patients treated with acyclovir or used for prevention, it was found that viruses with reduced sensitivity to valacyclovir are extremely rare, but can be detected in rare cases in patients with severe immunity, for example, bone marrow transplant recipients or organ, patients receiving chemotherapy for malignant neoplasms, and in HIV-infected patients.

Valaciclovir contributes to the relief of pain syndrome: reduces its duration and reduces the percentage of patients with pain caused by herpes zoster, including acute postherpetic neuralgia.

Pharmacokinetics:

Suction

After oral administration valaciclovir well absorbed from the gastrointestinal tract, quickly and almost completely turning into a acyclovir and valine.This transformation is probably carried out by the enzyme of the liver with valacyclovirhydrolase.

When taking valaciclovir in a dose of 1000 mg, the bioavailability of acyclovir is 54% and does not decrease with food intake. The pharmacokinetics of valacyclovir are not dose-dependent. The rate and degree of absorption decrease with increasing dose, resulting in a less proportional increase in the maximum concentration in the blood plasma (C_mOh) in comparison with the therapeutic range of doses and a decrease in bioavailability at doses above 500 mg.

Table 1. Results of assessing the pharmacokinetics of acyclovir when taking single doses of valaciclovir from 250 mg to 2000 mg by healthy volunteers with normal liver function

Pharmacokinetic parameters of acyclovir		250 mg (N = 15)	500 mg (N = 15)	1000 mg (N = 15)	2000 mg (N = 8)
FROM_mOh	μmol / l	9,78 ± 1,71	15,0 ±4,23	23,1 ±8,53	36,9 ± 6,36
FROM_mOh	mcg / ml	2,20 ± 0,38	3,37 ±0,95	5,20 ± 1,92	8,30 ± 1,43
T_mOh	hours (hours)	0,75 (0,75-1,5)	1,0 (0,75-2,5)	2,0 (0,75-3,0)	2,0 (1,5-3,0)
AUC	h · μmol / l	24,4 ± 3,65	49,3 ± 7,77	83,9 ±20,1	131 ±28,3
AUC	h · μg / ml	5,50 ±0,82	11,1 ± 1,75	18,9 ±4,51	29,5 ± 6,36

FROM_max- maximum concentration in blood plasma;

T_max - time to reach the maximum concentration in the blood plasma;

AUC - area under the pharmacokinetic curve "concentration-time". The value of C_max and AUC reflect the mean standard deviation. Values for T_max reflect the median value and range of values. The maximum concentration of valacyclovir in blood plasma is only 4% of the concentration of acyclovir, the median time of its attainment is 30 to 100 min after taking the drug. After 3 hours after taking the drug, the concentration of valaciclovir reaches the level of quantitation or lower.

Valaciclovir and acyclovir have similar pharmacokinetic parameters after a single and multiple administration. VZV and HSV significantly do not change the pharmacokinetics of valaciclovir and acyclovir after taking valacyclovir inwards.

Distribution

The degree of binding of valaciclovir to plasma proteins is very low (15%). The degree of penetration into the cerebrospinal fluid (CSF) is defined as the ratio AUC in the CSF to AUC in blood plasma and is about 25% for acyclovir and metabolite 8-hydroxyacyclovir (8-OH-ACV); about 2.5% for the metabolite 9- (carboxymethoxy) methyl guanine (CMMG).

Metabolism

After oral administration valaciclovir turns into acyclovir and L-valine through presystemic metabolism in the intestine and / or hepatic metabolism. Acyclovir is converted into small metabolites: CMMG under the influence of ethyl alcohol and aldehyde dehydrogenase; 8-OH-ACV under the influence of aldehyde oxidase. Approximately 88% of the total cumulative effect on blood plasma occurs in acyclovir, 11% - on CMMG and 1% - on the 8-OH-ACV. Valaciclovir and acyclovir are not metabolized by isoenzymes of the cytochrome P450 system.

Excretion

In patients with normal renal function, the half-life of acyclovir from the blood plasma after a single or multiple administration of valacyclovir is about 3 hours. Less than 1% of the accepted dose of valacyclovir is excreted by the kidneys unchanged. Valaciclovir is excreted from the body by the kidneys mainly in the form of acyclovir (more than 80% from the accepted dose) and a metabolite of acyclovir - CMMG.

Special patient groups

Patients with impaired renal function

Excretion of acyclovir correlates with renal function, the exposure of acyclovir increases with increasing severity of renal failure. In patients with terminal renal failure, the mean half-life of acyclovir after valaciclovir is approximately 14 hours compared to approximately 3 hours with normal renal function.

Exposure of acyclovir and its metabolites CMMG and 8-OH-ACV in plasma and CSF were evaluated in stable condition after multiple administration of valaciclovir in 6 patients with normal renal function (mean creatinine clearance 111 ml / min, range 91-144 ml / min) receiving 2000 mg every 6 hours, and in 3 patients with severe renal failure (mean creatinine clearance 26 ml / min, range 17-31 ml / min), receiving 1500 mg every 12 hours. With a severe degree of renal failure compared with normal renal function in blood plasma, as well as in CSF, the concentrations of acyclovir, CMMG and 8-OH-ACV were 2, 4 and 5-6 times higher, respectively. There was no difference in the degree of penetration of acyclovir in the CSF (defined as the ratio AUC in the CSF to AUC in blood plasma), CMMG or 8-OH-ACV between two populations with a severe degree of renal failure and normal renal function.

Patients with impaired hepatic function

Pharmacokinetic data show that in patients with hepatic impairment the rate of conversion of valaciclovir in acyclovir, but not the degree of this transformation. The half-life of acyclovir does not depend on liver function.

Pregnancy

In a study of the pharmacokinetics of valaciclovir and acyclovir in late pregnancy, an increase in daily AUC in a stable state with a daily intake of valacyclovir in a dose of 1000 mg per day, which is approximately 2 times higher AUC when administered to acyclovir in a dose of 1200 mg per day.

HIV infection

In patients with HIV infection, the distribution and pharmacokinetic characteristics of acyclovir following oral administration of one or more doses of 1000 mg or 2000 mg of valacyclovir remain unchanged compared to healthy volunteers.

Organ transplantation

The maximum concentration of acyclovir in patients after organ transplantation receiving 2000 mg of valaciclovir 4 times a day was comparable to or higher than the maximum concentration observed in healthy volunteers receiving the same dose. Set Daily Values AUC can be characterized as significantly higher.

Indications:

Adults and adolescents aged 12 to 18 years

- 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, including in adults with immunodeficiency.

- Prevention of infections caused by cytomegalovirus (CMV) and diseases after transplantation of parenchymal organs.

Adults

- Treatment of herpes zoster (Herpes zoster) and ophthalmic herpes zoster.

Contraindications:

- Hypersensitivity to valaciclovir, acyclovir or any other component of the drug.

- Children under 12 years.

- Children under 18 years of age in the treatment of herpes zoster and ophthalmic herpes zoster.

Carefully:

When used simultaneously with nephrotoxic drugs, renal failure, pregnancy, lactation, clinically expressed forms of HIV infection.

Pregnancy and lactation:

Fertility

In animal studies valaciclovir did not affect fertility. However, the use of high doses of acyclovir for parenteral administration caused testicular effects in rats and dogs.

Studies on the effects of valacyclovir on fertility in humans have not been conducted.However, there were no changes in the number, motility and morphology of spermatozoa in 20 patients after 6 months of daily use of valacyclovir in doses ranging from 400 mg to 1000 mg.

Pregnancy

There are limited data on the use of the drug Valaciclovir during pregnancy. The drug should be used during pregnancy only if the potential benefit to the mother exceeds the potential risk to the fetus.

Pregnant registries documented pregnancy outcomes in women who took valaciclovir or other preparations containing acyclovir (acyclovir is an active metabolite of valacyclovir), 111 and 1246 cases, respectively (of which 29 and 756 took drugs in the first trimester of pregnancy) were pregnancy outcomes recorded prospectively. Analysis of the data presented in the register of pregnant women exposed to acyclovir did not reveal an increase in the number of birth defects in their children compared to the general population, none of the malformations revealed specificity or patterns indicating a common cause.Since the register of pregnant women included a small number of women who took valaciclovir during pregnancy, it is impossible to make reliable and definite conclusions about the safety of valaciclovir during pregnancy.

Breastfeeding period

Acyclovir, the main metabolite of valacyclovir, penetrates into breast milk. After taking valacyclovir in a dose of 500 mg inside C_mOh in breast milk in 0,5-2,3 times (on average, 1,4 times) exceeded the corresponding concentrations of acyclovir in the blood plasma of the mother. Value relationship AUC Acyclovir in breast milk to AUC in the blood serum of the mother ranged from 1.4 to 2.6 (mean 2.2). 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 2 times a day, children who are breastfeeding are exposed to the same effects of acyclovir as if ingested 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 unchanged form was not determined in the blood plasma of the mother, breast milk or urine of the child.

A drug Valaciclovir should be administered with caution to women during breastfeeding.

Nevertheless acyclovir for intravenous administration is used to treat HSV in infants at a dose of 30 mg / kg / day.

Dosing and Administration:

A drug Valaciclovir is taken regardless of the meal, tablets should be washed down with water.

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)

Immunocompetent adults and adolescents aged 12 to 18 years

The recommended dose is 500 mg 2 times a day.

In case of relapse, treatment should last 3 or 5 days. In the case of primary herpes, which can occur in a more severe form, treatment should be started as early as possible, and its duration should be increased from 5 to 10 days. With relapses of HSV, the most appropriate is the prescription of the drug Valaciclovir in the prodromal period or immediately after the appearance of the first symptoms of the disease. The use of valaciclovir can prevent the development of the lesion if it is used at the first signs and symptoms of a relapse caused by HSV.

As an alternative treatment for labial herpes, the effective administration of the drug Valaciclovir in a dose of 2000 mg 2 times a day for 1 day. The second dose should be taken after approximately 12 hours (but not earlier than 6 hours) after taking the first dose. When using this dosing regimen, the duration of treatment should not exceed 1 day, as exceeding the duration of this course of treatment does not lead to additional clinical benefit.

Therapy should be started when the earliest symptoms of labial herpes (ie tingling, itching, burning) occur.

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

Immunocompetent adults and adolescents aged 12 to 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 adults with immunodeficiency, the recommended dose is 500 mg twice a day.

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

Prevention of infections caused by HSV and diseases after transplantation of parenchymal organs

Adults and adolescents aged 12 to 18 years

The recommended dose is 2000 mg 4 times a day, prescribed as soon as possible after transplantation. The dose should be lowered depending on the creatinine clearance. The duration of treatment is usually 90 days, but in patients with high-risk treatment can be extended.

Treatment of herpes zoster (Herpes zoster) and ophthalmic herpes zoster

Adults

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

Special patient groups

Children

Effectiveness of drug treatment Valaciclovir children have not been examined.

Elderly patients

It is necessary to take into account the possible violation of kidney function in elderly patients, the dose of the drug Valaciclovir should be adjusted accordingly.

It is necessary to maintain an adequate water-electrolyte balance.

Patients with impaired renal function

Dose of the drug Valaciclovir it is recommended to reduce in patients with severe renal dysfunction (see dosing regimen in Table 2). Such patients need to maintain an adequate water-electrolyte balance.

Table 2. Correction of the dose of the drug Valaciclovir for use in adults and adolescents aged 12 to 18 years with impaired renal function

Indications	Creatinine clearance, ml / min	Dose of the drug Valacyclovir
Herpes zoster and ophthalmic herpes zoster in immunocompetent adults (treatment)	not less than 50	1000 mg 3 times a day
	from 30 to 49	1000 mg twice a day
	from 10 to 29	1000 mg once a day
	less than 10	500 mg once a day
HSV (treatment)
Immunocompetent adults and adolescents aged 12 to 18 years	not less than 30	500 mg twice a day
	less than 30	500 mg 1 time per day
Labial herpes in immunocompetent adults and adolescents aged 12 to 18 years (treatment)	not less than 50	2000 mg twice daily
	from 30 to 49	1000 mg twice a day
	from 10 to 29	500 mg twice a day
	less than 10	500 mg once a day
HSV (prevention (suppression))
Immunocompetent adults and	not less than 30	500 mg 1 time per day
adolescents aged 12 to 18 years	less than 30	500 mg once every two days
Adults with immunodeficiency	not less than 30	500 mg twice a day
	less than 30	500 mg once a day
Prevention of infections caused by CMV in adults and adolescents aged 12 to 18 years	not less than 75	2000 mg 4 times a day
	from 50 to 75	1500 mg 4 times a day
	from 25 to 50	1500 mg 3 times a day
	from 10 to 25	1500 mg twice a day
	less than 10 or in patients on hemodialysis	1500 mg once a day

Additional information for indications: 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)

Experience with the drug Valaciclovir in children with a creatinine clearance less than 50 ml / min / 1.73 m² absent.

Additional information for indications: prevention of infections caused by CMV and diseases after transplantation of parenchymal organs

It is often necessary to determine the clearance of creatinine, especially at a time when the kidney function is changing rapidly, for example, immediately after transplantation or engraftment, while the dose of the drug Valaciclovir is adjusted in accordance with the creatinine clearance.

Additional information for indications: treatment of herpes zoster (Herpes zoster) and ophthalmic herpes zoster

A drug Valaciclovir should be used after hemodialysis in patients undergoing periodic hemodialysis.

Patients with impaired hepatic function

Based on the study using a single dose of valaciclovir 1000 mg in adult patients with cirrhosis of the liver of mild or moderate severity (with preserved synthetic liver function) dose adjustment Valaciclovir not required.

Pharmacokinetic data in adult patients with severe liver disorders (decompensated cirrhosis) functions with impaired liver synthetic function and presence portocaval anastomoses also indicate the need for correction of the dose Valaciclovir, but the clinical experience with these pathologies is limited.

Information about the doses more than 4000 mg per day for patients with infections caused by HSV and CMV, refer to "Cautions".

Side effects:

Adverse reactions listed below in accordance with the classification of the main systems and organs and occurrence frequency which has been determined as follows: very often: ≥ 1 to 10, often: ≥ 1 100 <1 10 infrequently: ≥ 1 to 1000 and <1 to 100, rare: ≥ 1 in 10,000 and <1 in 1000, extremely rare: <1 in 10,000.

Clinical Trials Data

From the nervous system

Often: headache.

From the gastrointestinal tract

Often: nausea.

Post-marketing research data

From the blood system and hematopoiesis

Rarely: leukopenia, thrombocytopenia. In general, leukopenia was observed in patients with reduced immunity.

From the immune system

Rarely: anaphylaxis.

From the nervous system and the psyche

Rarely: dizziness, confusion, hallucinations, depression of consciousness.

Rarely: agitation, tremor, ataxia, dysarthria, psychotic symptoms, 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 receiving high doses (8 g per day) of the drug Valaciclovir for the prevention of CMV infection, neurological reactions develop more often than when taking lower doses.

From the respiratory system and the mediastinum

Infrequently: dyspnea.

From the gastrointestinal tract

Rarely: discomfort in the abdomen, vomiting, diarrhea.

From the liver and biliary tract

Rarely: reversible violations of functional hepatic tests, which are sometimes regarded as manifestations of hepatitis.

From the skin and subcutaneous fat

Infrequently: rashes, including photosensitivity.

Rarely: itching.

Rarely: urticaria, angioedema.

From the urinary system

Infrequently: hematuria (often associated with other disorders of the kidneys).

Rarely: impaired renal function.

Rarely: acute renal failure, renal colic. Renal colic can be associated with impaired renal function.

Cases of precipitation of acyclovir crystals in the lumen of renal tubules have been reported. Adequate drinking regimen should be observed during treatment.

Other

In patients with severe impairment of immunity, especially in adults with advanced HIV infection receiving high doses of valaciclovir (8 g daily) for a long period of time, renal failure, microangiopathic hemolytic anemia, and thrombocytopenia (sometimes in combination) were observed. Similar complications were observed in patients with the same underlying and / or concomitant diseases, but not receiving valaciclovir.

Overdose:

Symptoms

Acute renal failure and neurologic disorders, including confusion, hallucinations, agitation, oppression of consciousness and coma, as well as nausea and vomiting, were observed in patients who received doses of valaciclovir exceeding those recommended.Similar conditions were more frequent in patients with impaired renal function and elderly patients who received repeated higher recommended doses of valaciclovir due to non-compliance with the dosing regimen.

Treatment

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

Interaction:

Clinically significant interactions are not established.

Acyclovir is excreted by the kidneys, mainly in 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 prescribing the drug Valaciclovir in a dose of 1000 mg and preparations cimetidine, probenecid, which are excreted in the same way as the drug Valaciclovir, there is an increase AUC acyclovir and, thus, decreases the renal clearance of acyclovir. Nevertheless, in view of the wide therapeutic index of acyclovir, the dose adjustment of the drug Valaciclovir not required.

In the treatment of labial herpes, the prevention and treatment of diseases caused by CMV, caution should be exercised in case of simultaneous use of the drug Valaciclovir at higher doses (4000 mg per day or more) and drugs that compete with acyclovir for the route of elimination, since there is a potential threat of a rise 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 immunosuppressant used in patients after organ transplantation) with the simultaneous use of these drugs.

Simultaneous use of the drug Valaciclovir with nephrotoxic drugs, including aminoglycosides, organic compounds of platinum, iodinated contrast medium, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus, should be performed with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function.

Special instructions:

Hydration

In patients with a risk of dehydration, especially in elderly patients,it is necessary to ensure an adequate water-electrolyte balance.

Application the patients with impaired renal function and the elderly patients

Because the acyclovir is excreted by the kidneys, it is necessary to reduce the dose of the drug Valaciclovir in patients with impaired renal function. In elderly patients, renal dysfunction may be observed, so a dose reduction for this group of patients should be considered. Both elderly patients and patients with impaired renal function are at increased risk of developing neurological complications, such patients need to ensure thorough medical supervision. As a rule, these reactions are mostly reversible in the case of drug discontinuation.

Treatment of labial herpes and prevention CMB-infections and diseases

The use of high doses of the drug Valaciclovir when liver function is impaired and liver transplantation

No data on drug use Valaciclovir in high doses (4000 mg per day and above) in patients with liver disease, so such patients high doses of the drug Valaciclovir should be administered with caution.Special studies to study the effect of the drug Valaciclovir when a liver transplant was not performed. However, it was found that the prophylactic administration of acyclovir in high doses reduces the manifestations of CMV infection and disease.

Use in genital herpes

Patients should be advised to refrain from having sex if symptoms occur, even if treatment with an antiviral drug Valaciclovir has already been started. Suppressive drug therapy Valaciclovir reduces the risk of transmission of genital herpes, but does not completely exclude the risk of infection and does not lead to complete cure. Drug therapy Valaciclovir it is recommended in combination with reliable means of barrier contraception.

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

During treatment, care should be taken when driving vehicles and engaging in other potentially hazardous activities.

Special studies were not conducted. It is necessary to take into account the clinical state of the patient and the profile of adverse reactions of valacyclovir when assessing a patient's ability to drive vehicles and mechanisms.

Form release / dosage:

Tablets, film-coated, 500 mg.

Packaging:

For 7, 10 or 14 tablets in a contoured cell pack of polyvinylchloride film and aluminum foil printed lacquered.

7, 10, 20, 30, 42, 50, 60 tablets in polymer cans made of polypropylene, low-density polyethylene with a cap of a first-tiered opening for vitamins and drugs, polypropylene, polyethylene with screw cap and lid screwed for vitamins and medicines or polymer cans made of polypropylene, low pressure polyethylene with a screw cap for vitamins and medicines.

Each bank, 1, 2, 3, 4, 5, 6 contour cell packs of 7 or 10 tablets, 1, 2, 3 contour cell packs of 14 tablets with instructions for use are placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-003553

Date of registration:11.04.2016

Expiration Date:11.04.2021

The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Information update date: & nbsp14.01.2017

Illustrated instructions

Instructions

Valaciclovir (Valacyclovir)