Valtrex
Valtrex: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Drug interactions
- 11. Analogs
- 12. Terms and conditions of storage
- 13. Terms of dispensing from pharmacies
- 14. Reviews
- 15. Price in pharmacies
Latin name: Valtrex
ATX code: J05AB11
Active ingredient: valacyclovir (valaciclovir)
Producer: GlaxoSmithKline Pharmaceuticals, SA (Poland)
Description and photo update: 2019-19-08
Prices in pharmacies: from 997 rubles.
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Valtrex is a drug belonging to the group of antiviral drugs.
Release form and composition
Valtrex is available in the form of film-coated tablets (6 pieces in a blister, 7 blisters in a cardboard box; 10 pieces in a blister, 1 blister in a cardboard box).
The active ingredient is valacyclovir hydrochloride, in 1 tablet 556 mg (corresponds to 500 mg of valacyclovir).
Auxiliary components: crospovidone - 28 mg; magnesium stearate - 4 mg; povidone K90 - 22 mg; microcrystalline cellulose - 70 mg; colloidal silicon dioxide - 2 mg.
The composition of the film shell: white opadry ~ 14 mg (titanium dioxide - 3.26 mg, polysorbate 80 - 0.14 mg, hypromellose - 9.48 mg, macrogol 400 - 1.12 mg); polishing (carnauba wax ~ 0.016 mg).
Pharmacological properties
Pharmacodynamics
Valacyclovir is an L-valine ester of acyclovir with antiviral properties. Acyclovir belongs to the analogs of the purine nucleoside (guanine).
In the human body, the active substance of Valtrex is quickly and almost 100% converted into valine and acyclovir, presumably with the participation of the enzyme valacyclovir hydrolase. Acyclovir is a specific inhibitor of herpes viruses showing in vitro activity against herpes simplex viruses (HSV) types 1 and 2, human herpes virus type 6, varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus.
Acyclovir slows down the synthesis of viral DNA immediately after participating in the process of phosphorylation and transition to the active form - acyclovir triphosphate. The first stage of phosphorylation is provided by the activity of virus-specific enzymes. For EBV, VZV and HSV, a similar enzyme is viral thymidine kinase, which is present exclusively in cells affected by the virus. In the case of cytomegalovirus, phosphorylation selectivity is partially supported indirectly by the product of the UL97 phosphotransferase gene. Thus, the selectivity of acyclovir can be largely explained by the need to activate this substance by a specific viral enzyme.
At the final stage of the phosphorylation process of acyclovir, which consists in the conversion from mono- to triphosphate, cellular kinases play an important role. Acyclovir is a competitive inhibitor of viral DNA polymerase and, as an analogue of a nucleoside, is incorporated into viral DNA, resulting in an obligate chain break, stopping DNA synthesis and, accordingly, blocking viral replication.
Resistance to acyclovir is usually attributed to a lack of thymidine kinase in the body, which provokes an excessive spread of the virus in the host. Occasionally, a decrease in sensitivity to acyclovir is associated with the appearance of viral strains in which the structure of DNA polymerase or viral thymidine kinase is disrupted. The virulence of these varieties of the virus is similar to that of its wild strain.
The results of an extensive study of VZV and HSV strains selected from patients who underwent treatment with acyclovir or used it for prophylactic purposes confirm that viruses with reduced sensitivity to valacyclovir are very rare, but in some cases they can be detected in patients with severely impaired immunity. in particular, HIV-infected patients, patients undergoing chemotherapy for malignant neoplasms, and organ or bone marrow transplant recipients.
Valacyclovir provides relief of pain syndrome: it reduces its duration and reduces the percentage of patients with pain caused by herpes zoster, including acute postherpetic neuralgia.
Pharmacokinetics
After oral administration, valacyclovir is well absorbed from the gastrointestinal tract, rapidly and almost 100% decomposing into two substances: valine and acyclovir. This biotransformation is presumably carried out with the participation of the hepatic enzyme valacyclovir hydrolase.
When the drug is taken at a dose exceeding 1000 mg, the bioavailability of acyclovir is 54% and does not decrease when Valtrex is taken together with food. The pharmacokinetic parameters of valacyclovir are not dose-dependent. The degree and rate of absorption decrease with increasing dose, which leads to a less proportional increase in the maximum concentration in blood plasma compared to the recommended dose range and a decrease in bioavailability when taking Valtrex at doses above 500 mg.
A study evaluating the pharmacokinetic parameters of acyclovir with a single dose of valacyclovir at doses of 250-2000 mg to healthy volunteers with normal liver function gave the following results:
- when taking 250 mg: the maximum concentration in blood plasma is 9.78 ± 1.71 μmol / l (2.2 ± 0.38 μg / l), the time to reach the maximum concentration in the blood plasma is 0.75 hours (varies in the range 0.75-1.5 hours), the area under the concentration-time pharmacokinetic curve (AUC) is 24.4 ± 3.65 μmol. h / l (5,5 ± 0,82 g. h / ml);
- when taking 500 mg: the maximum concentration in blood plasma is 15 ± 4.23 μmol / l (3.37 ± 0.95 μg / l), the time to reach the maximum concentration in blood plasma is 1 hour (varies in the range of 0.75‒ 2.5 hours), the area under the concentration-time pharmacokinetic curve (AUC) is 49.3 ± 7.77 μmol. h / L (11,1 ± 1,75 g. h / ml);
- when taking 1000 mg: the maximum concentration in blood plasma is 23.1 ± 8.53 μmol / l (5.2 ± 1.92 μg / l), the time to reach the maximum concentration in blood plasma is 2 hours (varies in the range of 0, 75-3 hours), the area under the concentration-time pharmacokinetic curve (AUC) is 83.9 ± 20.1 μmol. h / L (18,9 ± 4,51 g. h / ml);
- when taking 2000 mg: the maximum concentration in blood plasma is 36.9 ± 6.36 μmol / l (8.3 ± 1.43 μg / l), the time to reach the maximum concentration in blood plasma is 2 hours (varies in the range 1, 5-3 hours), the area under the concentration-time pharmacokinetic curve (AUC) is 131 ± 28.3 μmol. h / L (29,5 ± 6,36 pg. h / mL).
The maximum concentration and AUC values correspond to the mean standard deviation. Time to peak plasma concentration values correspond to the median value and reflect the range of values.
The maximum content of valaciclovir in blood plasma is only 4% of the content of acyclovir, and the median time to reach it varies from 30 to 100 minutes after taking Valtrex. After 3 hours after ingestion of the drug, the concentration of its active ingredient reaches a level that can be quantified or lower. Valacyclovir and acyclovir are characterized by similar pharmacokinetic parameters both after single and multiple doses. HSV and VZV do not significantly affect the pharmacokinetics of acyclovir and valacyclovir after oral administration of the drug.
Valacyclovir binds to blood plasma proteins slightly (about 15%). The degree of penetration into the cerebrospinal fluid (CSF) is defined as the ratio of AUC in CSF to AUC in blood plasma. It is equal to about 2.5% for the metabolite 9- (carboxymethoxy) methyl-guanine (CMMG) and about 25% for acyclovir itself and its metabolite 8-hydroxyacyclovir (8-OH-ACV).
When taken orally, valacyclovir is converted to L-valine and acyclovir during the processes of hepatic metabolism and / or presystemic metabolism in the intestine. During the biotransformation of acyclovir, small metabolites are formed: 8-OH-ACV with the participation of aldehyde oxidase and CMMG with the participation of aldehyde dehydrogenase and ethyl alcohol. In a study of the total cumulative effect of the drug on blood plasma, approximately 88% of it is accounted for by acyclovir, 11% by CMMG and 1% by 8-OH-ACV. Valacyclovir and acyclovir are not metabolized by isozymes of the cytochrome P 450 system.
In patients with normal renal function, the half-life of acyclovir from blood plasma after a single or multiple dose of Valtrex is approximately 3 hours. Less than 1% of the dose of valacyclovir taken is excreted in the urine unchanged. The active substance of Valtrex is excreted through the kidneys mainly in the form of acyclovir (more than 80% of the dose entered into the body) and its metabolite CMMG.
A correlation was found between the elimination of acyclovir and renal function; therefore, the exposure of this substance increases with an increase in the severity of renal dysfunction. In patients with end-stage renal failure, the half-life of acyclovir after taking Valtrex averages approximately 14 hours compared to approximately 3 hours in patients with normal renal function.
Exposures of acyclovir and its main metabolites 8-OH-ACV and CMMG in CSF and blood plasma were determined in a stable state after repeated administration of the drug in 6 patients without renal dysfunction (average CC is 111 ml / min, the range of variation is 91‒ 144 ml / min) and who took Valtrex at a dose of 2000 mg every 6 hours, as well as in 3 patients with severe renal failure (on average, CC is 26 ml / min, the range of variation is 17-31 ml / min), who took Valtrex at a dose of 1500 mg every 12 hours.
In patients with severe renal failure compared with patients with normal renal function, the concentrations of acyclovir, 8-OH-ACV and CMMG in blood plasma and CSF were 2, 5-6 and 4 times higher, respectively. The degree of penetration of acyclovir and its metabolites into the CSF practically did not differ in all cases.
Pharmacokinetic data indicate that in patients with hepatic insufficiency, the rate of conversion of valacyclovir to acyclovir decreases, but this does not affect the degree of this conversion. The half-life of acyclovir is not determined by liver function.
Pharmacokinetic studies of the effect of valacyclovir and acyclovir on the body of women in late pregnancy confirm an increase in the daily AUC value in an equilibrium state with a daily intake of Valtrex at a daily dose of 1000 mg, approximately 2 times higher than the AUC with oral administration of acyclovir at a daily dose of 1200 mg.
In patients with HIV infection, the pharmacokinetic parameters and distribution of acyclovir after oral administration of one or several doses of 1000 mg or 2000 mg of Valtrex practically do not change compared with healthy volunteers.
The maximum content of acyclovir in patients after organ transplantation who took valacyclovir at a dosage of 2000 mg 4 times a day was higher or comparable with the maximum content of this substance in the body of healthy volunteers who took a similar daily dose of valacyclovir. Certain daily AUC values were markedly higher.
Indications for use
For adult patients, the indications for the use of Valtrex tablets are:
- Treatment of infections of the mucous membranes and skin caused by the herpes simplex virus (including labial herpes, as well as recurrent and newly diagnosed genital herpes);
- Treatment of shingles (the drug has a pain relieving effect, helps to reduce the percentage of patients with pain caused by shingles, including postherpetic and acute neuralgia, reduces the duration of the disease);
- Prevention of transmission of genital herpes to a healthy sexual partner (as suppressive therapy in combination with safe sex);
- Prevention of recurrence of infections of the mucous membranes and skin caused by the herpes simplex virus (including genital).
The appointment of Valtrex to adults and adolescents over the age of 12 is advisable for the prevention of cytomegalovirus, opportunistic and other herpesvirus infections after organ transplantation, as well as the reaction of acute transplant rejection (in persons with kidney transplants).
Contraindications
- Age less than 12 years (when Valtrex is prescribed for the prevention of cytomegalovirus infection after transplantation);
- Age less than 18 years (for all other indications);
- Hypersensitivity of the patient to acyclovir, valacyclovir and other components of the drug.
According to the instructions, Valtrex is prescribed with caution to patients suffering from renal insufficiency and clinically severe forms of HIV infection, as well as with simultaneous therapy with nephrotoxic drugs.
Instructions for the use of Valtrex: method and dosage
Taking the drug does not depend on food intake, the tablets should be taken with water.
The recommended dosage regimen of Valtrex for:
- Treatment of infections caused by the herpes simplex virus (HSV) as therapy for adults - 2 times a day, 500 mg for 5 days. If the onset of the disease is more severe, it is recommended to start therapy as early as possible; it is also possible to increase the duration of therapy to 10 days. If relapses occur, the duration of treatment can be up to 3-5 days. The best option for recurrent HSV is the appointment of Valtrex in the prodromal period or immediately after the first signs of the disease appear;
- Alternative therapy for labial herpes for adults - 2 g 2 times a day. It is recommended to take the second dose after about 12 hours (but not earlier than 6 hours) after the first dose. In this case, the duration of therapy is 1 day. It is recommended to start using Valtrex at the earliest symptoms of the disease (itching, tingling, burning);
- Shingles treatment for adult patients - 3 times a day, 1 g for 7 days;
- Suppression of recurrent infections caused by HSV in adults with preserved immunity - 500 mg once a day, in patients with immunodeficiency - 500 mg 2 times a day;
- Prevention of transmission of genital herpes to a healthy sexual partner. Infected immunocompetent patients with relapses no more than 9 times a year - 500 mg once a day every day, the duration of therapy is 1 year or more;
- Prevention of cytomegalovirus infection after transplantation in adult patients and adolescents over 12 years of age - 2 g 4 times a day, while therapy should begin immediately after transplantation. The dose is reduced based on the creatinine clearance rates. The duration of therapy is 90 days, however, an increase in the duration of treatment is allowed for patients at high risk.
Patients with impaired liver function do not need to adjust the Valtrex dose, however, clinical experience with severe impaired liver function, impaired liver synthetic function and the presence of porto-caval anastomoses is limited.
In patients with impaired renal function:
- Shingles therapy: with creatinine clearance of 15-30 ml / min - 1 g 2 times per knock, with creatinine clearance less than 15 ml / min - 1 g 1 time per day;
- Therapy of infections caused by the herpes simplex virus: with creatinine clearance less than 15 ml / min - 500 mg once a day;
- Therapy for labial herpes (according to the scheme 2 g 2 times within 1 day): with creatinine clearance 31-49 ml / min - 1 g 2 times during the day, with creatinine clearance 15-30 ml / min - 500 mg 2 times during days, with creatinine clearance less than 15 ml / min - 500 mg once;
- Prevention of recurrence of infections caused by the herpes simplex virus (dose adjustment is recommended when creatinine clearance is less than 15 ml / min): for patients with normal immunity - 250 mg once a day, for patients with reduced immunity - 500 mg once a day;
- Reducing the risk of contracting genital herpes in a healthy sexual partner: with creatinine clearance less than 15 ml / min - 250 mg once a day;
- Prevention of cytomegalovirus infection after transplantation: with creatinine clearance 75 ml / min or more - 2 g 4 times a day, with creatinine clearance 50-75 ml / min - 1.5 g 4 times a day, with creatinine clearance 25-50 ml / min - 1.5 mg 3 times a day, with creatinine clearance 10-25 ml / min - 1.5 g 2 times a day, with creatinine clearance less than 10 ml / min or dialysis - 1.5 g 1 time per day.
When treating patients on hemodialysis, the drug is prescribed in the same dose as for patients with creatinine clearance less than 15 ml / min (Valtrex tablets are recommended to be taken immediately after the hemodialysis procedure).
Elderly patients do not need dose adjustment, except in cases of severe renal impairment.
There is no data on the use of Valtrex in children under 12 years of age.
Side effects
According to clinical studies:
- Gastrointestinal tract: often - nausea;
- Nervous system: often - headache.
According to the results of post-marketing research:
- Immune system: very rarely - anaphylaxis;
- Liver and biliary tract: very rarely - violations of functional liver tests (are reversible), which in some cases are interpreted as manifestations of hepatitis;
- Respiratory system and mediastinal organs: infrequently - shortness of breath;
- Urinary system: rarely - renal dysfunction; very rarely - renal colic (may be associated with impaired renal function), acute renal failure;
- Nervous system and psyche: rarely - confusion, depression of consciousness, dizziness, hallucinations; very rarely - tremor, dysarthria, convulsions, agitation, encephalopathy, ataxia, psychotic symptoms, coma. As a rule, the listed symptoms are reversible and in most cases are observed in patients with impaired renal function or against the background of other predisposing conditions;
- Digestive system: rarely - vomiting, abdominal discomfort, diarrhea;
- Skin and subcutaneous fat: infrequently - rashes (including manifestations of photosensitization), rarely - itching, very rarely - angioedema, urticaria;
- Blood and hematopoietic system: very rarely - thrombocytopenia, leukopenia (in most cases in patients with reduced immunity);
- Other: in patients with severe impaired immunity (especially in adult patients suffering from an advanced stage of HIV infection and taking high doses of valacyclovir (8 g per day) for a long period of time), cases of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure have been recorded. The described complications were observed in patients with the same underlying and concomitant diseases who were not treated with valacyclovir.
Overdose
Patients taking valacyclovir in doses exceeding therapeutic ones may experience symptoms such as nausea, vomiting, neurological disorders (confusion, depression of consciousness, agitation, hallucinations, coma), acute renal failure. Similar signs were more common in patients with renal dysfunction and in elderly patients who repeatedly took Valtrex in doses exceeding the recommended ones due to non-compliance with the dosage regimen.
In case of overdose, patients should remain under strict medical supervision. It is possible to remove most of the acyclovir entering the body through hemodialysis.
special instructions
Adjustment of the Valtrex dose should be carried out in accordance with the degree of renal dysfunction. Patients suffering from renal failure should be provided with careful medical supervision, since this category of individuals has an increased risk of neurological complications (in most cases, such manifestations disappear after discontinuation of therapy).
The use of Valtrex in order to reduce the risk of transmission of genital herpes should be combined with safe sex, since the drug does not completely eliminate the risk of infection and does not contribute to a complete cure.
High doses of the drug (4 g per day or more) should be prescribed to patients with liver disease with caution.
When prescribing Valtrex to patients at risk of dehydration (especially the elderly), it is recommended to maintain the water balance in the body.
The patient's ability to drive a vehicle and other driving mechanisms during therapy is assessed taking into account his clinical condition and the side effect profile of valacyclovir.
Application during pregnancy and lactation
In the course of experiments on animals, the absence of the effect of valacyclovir on fertility was found. However, high-dose parenteral administration of acyclovir provoked testicular affects in dogs and rats.
Studies regarding the effect of Valtrex on fertility in humans have not been conducted. However, in 20 patients after 6 months of daily intake of the drug in the dose range of 400–1000 mg, there were no changes in morphology, motility, and sperm count.
There is limited information on the use of the drug during pregnancy. Valtrex should be prescribed during pregnancy only in cases where the potential benefits of treatment for the mother significantly outweigh the potential risks to the fetus.
There are documented reports of pregnancy outcomes in women taking Valtrex or other drugs that include acyclovir. Of these, 111 and 1246 cases, respectively (of which 29 and 756 patients received drugs in the first trimester of pregnancy) were pregnancy outcomes registered prospectively. Analysis of the study results did not confirm an increase in the number of congenital malformations in their children compared to the entire population. No specific malformations or patterns were found to indicate a common cause. However, a small number of pregnant women were included in the study, therefore, reliable and definite conclusions about the advisability and safety of using Valtrex during pregnancy cannot be made.
Acyclovir is determined in breast milk. After oral administration of Valtrex in a dose of 500 mg, the maximum concentration of valaciclovir in breast milk is 0.5-2.3 times (mean value 1.4 times) higher than the corresponding concentration of acyclovir in the mother's blood plasma. The ratio of the AUC values of a given substance in breast milk to the AUC in the blood serum of a nursing mother ranges from 1.4 to 2.6 (average 2.2). The average level of acyclovir in breast milk was 9.95 μmol / L (2.24 μg / ml). When a mother takes Valtrex at a dosage of 500 mg 2 times a day, children who eat breast milk are exposed to the same effect of acyclovir as when it is taken orally at a daily dose of about 0.61 mg / kg. The half-life of acyclovir from breast milk is identical to its value for blood plasma.
Valacyclovir in unchanged form was not detected in the child's urine, breast milk or mother's blood plasma. During lactation, Valtrex is recommended to be prescribed with caution. However, acyclovir is given intravenously at a daily dose of 30 mg / kg for the treatment of HSV in infants.
Drug interactions
No clinically significant interactions have been reported.
It is recommended to be careful when prescribing simultaneous therapy with Valtrex (at a dose of 4 g per day or more) and drugs that compete with acyclovir for the elimination route, due to the possible risk of an increase in the plasma concentration of the drugs used or their metabolites.
Also, caution requires the combined use of Valtrex (at a dose of 4 g per day or more) with drugs that affect other renal functions (for example, tacrolimus, cyclosporine).
Analogs
Valtrex analogs are: Valvir, Valtsikon, Valacyclovir, Valacyclovir Canon, Valogard, Virdel.
Terms and conditions of storage
Store at a temperature not exceeding 30 ° C out of reach of children.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Valtrex
Reviews about Valtrex are very diverse and can be both positive and negative. He helped some patients forget about the unpleasant symptoms of herpes for a long time and coped well with the treatment of the disease, while others complain of their reappearance within a couple of weeks after completing the course of treatment. There are also recommendations to take Valtrex for recurrent herpes.
Doctors usually speak well of the drug, noting its high effectiveness with strict adherence to the treatment regimen. Also, Valtrex is convenient to use due to the lower frequency of reception compared to analogues. It is believed to be able to successfully combat diseases such as herpes-associated erythema multiforme, genital herpes, and chickenpox. The drug is characterized by low toxicity, a minimum number of side reactions and quickly eliminates rashes on the lips. However, many people do not like the high cost of Valtrex.
Price for Valtrex in pharmacies
The average price for Valtrex is 1,051-1450 rubles (the package contains 10 tablets) or 2952-3625 rubles (the package contains 42 tablets).
Valtrex: prices in online pharmacies
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Drug name Price Pharmacy |
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Valtrex 500 mg film-coated tablets 10 pcs. 997 RUB Buy |
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Valtrex tablets p.p. 500mg 10 pcs. 1061 RUB Buy |
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Valtrex 500 mg film-coated tablets 42 pcs. 2876 RUB Buy |
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Valtrex tablets p.p. 500mg 42 pcs. RUB 3010 Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
