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

Components:	Amount of mg / tablet
*Core:*
Active substance:
Valaciclovir hydrochloride	556
(in terms of valaciclovir)	500
Excipients:
Microcrystalline cellulose	70
Crospovidone	28
Povidone-K90	22
Magnesium stearate	4
Silica colloidal dioxide	2
*Film sheath:*
Fell as YS-1-18043	about 14
Polishing:
Carnauba Wax	about 0.016
Inks for printing:
Brilliant blue, 5312 (FT203)	about 0.07 μl

Notes:

1. Opadry YS-1-18043 contains: hypromellose - 9.48 mg; titanium dioxide - 3.26 mg; macrogol-400-1.12 mg; polysorbate-80 - 0.14 mg.

2. Inks for printing Brilliant blue, 5312 (FT203) contain: ethanol (95%), propylene glycol, shellac, dye, brilliant blue (E133), sodium lactate, dimethicone.

Description:Bhollow, oblong, biconvex tablets without any risks, on one side the inscription is written in blue ink GX CF1. The core is from white to 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, it is an L-valine 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), Epstein-Barr virus (EBV) and human herpesvirus type 6.

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 extensive study of HSV and BWV strains selected from patients who received acyclovir therapy or applied it for prophylaxis, 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 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 speed and degree of absorption decrease with increasing dose, resulting in a less proportional increase in the maximum concentration in the blood plasma (FROM_max) in comparison with the therapeutic range of doses and a decrease in bioavailability at doses above 500 mg.

Table 1. Results of the evaluation of the pharmacokinetics of acyclovir in single doses valacyclovir 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 mi (N = 15)	2000 mg (N = 8)
FROM_max	umol/l	9,78 ± 1,71	15,0 ± 4,23	23,1 ± 8,53	36,9 ± 6,36
FROM_max	mcg / l	2,20 ± 0,38	3,37 ± 0,95	5,20 ± 1,92	8,30 ± 1,43
T_max	hours (hours)	0,75	1,0	2,0	2,0
T_max	hours (hours)	(0,75 - 1,5)	(0,75- 2,5)	(0,75 - 3,0)	(1,5 - 3,0)
AUC	h·umol/l	24,4 ± 3,65	49,3 ± 7,77	83,9 ± 20,1	131 ± 28,3
AUC	h·mcg / ml	5,50 ± 0,82	11,1 ± 1,75	18,9 ± 4,51	29,5 ± 6,36

FROM_m_Oh - 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 values of C_max and AUC reflect the mean standard deviation.

Values for T_m_Oh 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 presystem 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 valaciclovir 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% of the dose taken) and the 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 an increase in the severity of renal failure. In patients with terminal stage of renal failure, the mean half-life of acyclovir after valacyclovir is approximately 14 hours compared to approximately 3 hours with normal renal function.

Expositions of acyclovir and its metabolites CMMG and 8-OH-ACV in blood plasma and CSF were evaluated in a stable state after multiple administration of valaciclovir in 6 patients with normal renal function (mean creatinine clearance 111 ml / min,the range of 91-144 ml / min) received 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 severe renal failure compared with normal renal function in blood plasma, as well as in CSF, acyclovir concentrations, 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 of AUC to CSF to AUC in blood plasma), CMMG or 8-OH-ACV between two populations with severe 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

A study of the pharmacokinetics of valaciclovir and acyclovir in late pregnancy established an increase in the daily AUC value in a stable state with a daily intake of valaciclovir 1000 mg / day, which was approximately 2 times higher than the AUC when administered at a dose of 1200 mg per day of acyclovir.

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 received 2000 mg valaciclovir 4 times a day, was comparable or higher than the maximum concentration, observed in healthy volunteers who received the same dose. Set Daily Values AUC can be characterized as significantly higher.

Indications:

Adults and adolescents aged 12 to 18 years:

- lTreatment 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);

- PThe re-infection (suppression) of recurrences of infections of the skin and mucous membranes caused by HSV, including genital herpes, including in adults with immunodeficiency;

- Pthe prevention of infections caused by cytomegalovirus (CMV), and diseases after transplantation of parenchymatous opganas.

Adults:

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

Contraindications:

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

- children's age till 12 years;

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

Carefully:

In patients with renal insufficiency; patients with clinically expressed forms of HIV infection; while taking nephrotoxic medicines at the same time.

Pregnancy and lactation:

Fertility

In animal studies valaciclovir did not affect fertility. However, the use of high doses of acyclovir with parenteral administration caused testicular affects 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 Valtrex® 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 registers documented pregnancy outcomes in women taking Valtrex® or other drugs containing acyclovir (acyclovir is an active metabolite of the drug Valtrex®), 111 and 1246 observations, 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 as compared to the general population, none of the developmental defects showed specificity or patterns indicating common cause. Since the register of pregnant women included a small number of women who took valaciclovir during pregnancy, then certain and definite conclusions about security the use of valaciclovir during pregnancy can not be done.

Breastfeeding period

Acyclovir, the main metabolite of valacyclovir, penetrates into breast milk. After taking valacyclovir in a dose of 500 mg inside C_max 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. The ratio of AUC values of acyclovir in breast milk to AUC in the mother's serum 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 twice a day, children who are breastfeeding, are exposed to the same effects of acyclovir as when taken orally at a dose of about 0.61 mg / kg / day. The half-life of acyclovir from breast milk is the same as from plasma.

Valacyclovir in unchanged form was not detected in blood plasma mother, breast milk or urine of a child. Valtrex® 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:

The preparation Valtrex® is taken regardless of the meal, the tablets should be washed down with water.

Treatment of infection of the skin and mucous membranes caused by HSV, include the newly identified 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, Valtrex® in the prodromal period or immediately after the appearance of the first symptoms of the disease is considered to be the most correct. 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, valtrex® in a dose of 2000 mg 2 times a day for 1 day is effective. 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 the excess of 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 infection 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 CMV 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 treatment Valtrex® in children was not examined.

Elderly patients

It is necessary to take into account the possible violation of renal function in elderly patients, the dose of Valtrex® should be adjusted accordingly.

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

Patients with impaired renal function

The dose of Valtrex® should be reduced 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 a dose of Valtrex® for use in adults and adolescents aged 12 to 18 years with impaired renal function

Indications	Creatinine clearance, ml / min	The dose of Valtrex®
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 1 time per 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 2 times and 24 hours
Immunocompetent adults and adolescents aged 12 to 18 years	less than 30	500 mg once a day
Labial herpes in Immunocompetent adults and adolescents aged 12 to 18 years (treatment)	Not less than 50	2000 mg twice daily
	30 to 49	1000 mg twice a day
	10 to 29	500 mg twice a day
	Less than 10	500 mg once a day
HSV (prevention (suppression))
ANDMmunokompetent Adults and adolescents aged 12 to 18 years	not less than 30	500 mg 1 time per day
	less than 30	500 mg once every two days
Adults with immunodeficiency	not less than 30	500 mg 2 times and 24 hours
Adults with immunodeficiency	less than 30	500 mg 1 time per day
Preventing CMV infection in of adults and teenagers at ages 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 daily

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 Valtrex® in children with creatinine clearance less than 50 ml / min / 1.73 m² absent.

Additional information for the indication: 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 of the graft, with the dose of Valtrex® adjusted according to creatinine clearance.

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

Valtrex® 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 mild or moderate severity (with preserved synthetic function of the liver), the dose adjustment of Valtrex® is not required.

Pharmacokinetic data in adult patients with severe liver dysfunction (decompensated cirrhosis), with a violation of the synthetic function of the liver and the presence of portocaval anastomoses also do not indicate the need for correction of Valtrex dose, 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:

Undesirable reactions are listed below in accordance with the classification of the main systems and organs and the frequency of occurrence, which was defined as follows: very often: ≥ 1 to 10, often: ≥ 1 to 100 and <1 to 10, infrequently: ≥1 per 1000 and <1 per 100, rarely: ≥ 1 per 10000 and <1 per 1000, very rarely: <1 per 10000.

Clinical Trials Data

From the nervous system

Often: headache.

FROMabout the side of the gastrointestinal tract

Often: nausea.

Post-marketing research data

From the blood system and hematopoiesis

Rarely: leukopenia, thrombocytopenia. AT mainly, 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, seizures, 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 (8 g per day) of Valtrex® for the prevention of CMV infection, neurologic reactions develop more often than with 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 functional liver tests, which sometimes regarded as manifestations of hepatitis.

From the skin and subcutaneous fat

Infrequently: Rashes, including photosensitivity manifestations.

Rarely: itching.

Rarely: hives, angioedema.

From the urinary system

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

Rarely: impaired renal function.

Rarely: acute renal insufficiency, renal colic. Renal colic can be associated with impaired renal function. Crystalline deposition was reported Acyclovir in the lumen of the renal tubules.

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, there have been cases of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia (sometimes in combination). Similar complications were noted in patients with the same underlying 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 Valtrex®.

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 the appointment of Valtrex® in a dose of 1000 mg and drugs cimetidine, probenecid, which are excreted in the same way as the preparation Valtrex®, there is an increase AUC acyclovir and, thus, decreased kidney clearance acyclovir. Topics not less, due to the wide therapeutic index of acyclovir, correction of Valtrex® dose is 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 Valtrex^®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 inactive mof mycophenolate mycophenolate mofetil (an immunosuppressant used in patients after organ transplantation) with the simultaneous use of these drugs.

Simultaneous application Valtrex® 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 at risk of dehydration, especially in elderly patients, an adequate water-electrolyte balance must be ensured.

Use in 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 Valtrex^® 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 of CMV infections and diseases

The use of high doses of Valtrex® in cases of impaired liver function and after liver transplantation

No data on the use of Valtrex^® in high doses (4000 mg in day and above) in patients with liver disease, so such patients high dose Valtrex^® should be administered with caution.

Specials Studies on the study of Valtrex® during liver transplant were not carried out. 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 abstain from sexual contact if there are symptoms, even if treatment with the antiviral drug Valtrex® has already been started. Suppressive therapy with Valtrex^® reduces the risk of transmission of genital herpes, but does not completely exclude the risk of infection and does not lead to complete cure. Therapy with Valtrex^® it is recommended in combination with reliable means of barrier contraception.

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

It is necessary to take into account the clinical state of the patient and the profile of adverse reactions of valacyclovir in assessing the patient's ability to drive or move vehicles.

Form release / dosage:

Tablets, film-coated, 500 mg.

Packaging:

For 10 tablets in PVC / aluminum foil blisters. For 1 blister, along with instructions for medical use in a cardboard box.

For 6 tablets in PVC / aluminum foil blisters. By 7 blisters together with instructions for medical use in a cardboard box.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:П N015441 / 01

Date of registration:27.04.2009 / 18.05.2012

Expiration Date:Unlimited

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Manufacturer: & nbsp

GlaxoSmithKline Pharmaceuticals, S.A. Poland

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp20.01.2017

Illustrated instructions

Instructions

Valtrex® (Valtrex®)