Valacyclovir:(2S)-[2-[2-Amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]ethyl]-2-amino-3-methylbutanoate hydrochloride is an antiviral drug. It blocks the synthesis of viral DNA and viral replication. In the human body valacyclovir is converted to acyclovir and valine.
Aciclovir has specific activity against herpes simplex viruses of types I and II, Varicella zoster virus, cytomegalovirus, Epstein-Barr virus and human herpes virus type VI. Due to phosphorylation acyclovir transforms into active acyclovir triphosphate, which competitively inhibits the synthesis of viral DNA. The first stage of phosphorylation requires the activity of a virus-specific enzyme. For herpes simplex virus, Varicella zoster virus and Epstein-Barr virus this is a viral thymidine kinase available only in cells infected with the virus. In cytomegalovirus infection, acyclovir phosphorylation is mediated by a product of the UL97 phosphotransferase gene.
After oral administration valacyclovir is well absorbed in the gastrointestinal tract (GIT) and is rapidly and almost completely converted to acyclovir and valine. Bioavailability of acyclovir when taking 1 g of valacyclovir is 54% and is not reduced by simultaneous food intake.
The maximum concentration of acyclovir after a single administration of 250 mg – 1 g of valacyclovir averages 15-25 µmol/L and is reached 1.6-2.1 hours after administration; after 3 hours valacyclovir in plasma is not determined. Valacyclovir’s binding to plasma proteins is 13-18%. Half-life of acyclovir after single and repeated use is about 3 hours.
Valacyclovir is excreted by the kidneys, mainly as acyclovir and its metabolite 9carboxymethoxymethylguanine‑. Acyclovir is widely distributed in tissues and body fluids, including brain, kidney, lung, liver, aqueous humor, tear fluid, intestine, muscle, spleen, uterus, vaginal mucosa and secretion, semen, amniotic fluid, cerebrospinal fluid (CSF) (50% of concentration in plasma), herpes vesicle fluid. The highest concentrations are produced in the kidneys, liver, and intestine. Passes through the placenta and into breast milk.
Colds, Herpes, Chickenpox, Cytomegalovirus infection, Skin itch
The drug is used for:
- Lip herpes,
- genital herpes (primary and recurrent infection; long-term suppressive therapy of recurrent genital herpes in persons with immunodeficiency, including. HIV infection; reduction of risk of sexual partner transmission),
- herpes zoster.
In adults and children over 12 years: prophylaxis of cytomegalovirus infection in organ transplants.
1 film-coated tablet contains:
the active ingredient:
Valacyclovir hydrochloride 556.275 mg, equivalent to valacyclovir 500 mg.
Microcrystalline cellulose (PH 101) 109.425 mg,
crospovidone 7 mg,
dye indigo carmine (E132) 0.3 mg,
povidone (K 30) 18 mg,
povidone (K 90D) 2 mg,
magnesium stearate 7 mg,
purified water q.s.*
DyeOpadray02C50740 blue 21 mg, purified water q.s.*
Composition of Opadray 02C50740 dye blue: Hypromellose 5 cP (E464) 13.02 mg, titanium dioxide (E171) 5.46 mg, macrogol/PEG 400 1.05 mg, macrogol/PEG 6000 0.63 mg, indigo carmine dye (E132) 0.42 mg, polysorbate 80 (E433) 0.42 mg
How to take, the dosage
Orally (regardless of meals).
For the treatment of herpes zoster in adults 1 g 3 times a day for 7 days.
For the treatment of diseases caused by Herpes simplex virus in adults, Valacyclovir is prescribed at 500 mg 2 times per day. In cases of relapses, treatment should be given for 3 or 5 days. In more severe primary cases, treatment should be started as soon as possible, and its duration should be increased from 5 to 10 days. In relapsed cases, valacyclovir should be given optimally in the prodromal period or immediately after the onset of the first symptoms of the disease.
As an alternative treatment for herpes of the lips (lip fever), it is effective to prescribe valacyclovir in a dose of 2 g 2 times for 1 day. The second dose should be taken approximately 12 hours (but not earlier than 6 hours) after the first dose. With this dosing regimen, the duration of treatment should not exceed 1 day because it provides no additional clinical benefit. Therapy should be started when the earliest symptoms of lip fever appear (i.e., tingling, itching, burning).
For prevention (suppression) of recurrent infections caused by Herpes simplex virus, in adults with normal immunity indicators, it is prescribed in a dose of 500 mg once a day. In adults with immunodeficiency it is recommended to prescribe 500 mg 2 times per day. The duration of treatment is 4-12 months. There are no data on prevention of infection in other patient populations.
In case of renal insufficiency the dosing regimen is established depending on creatinine clearance (CK) and indications.
Indications CK (ml/min)Dose of valacyclovirHerpes herpes15-30 ml/min1 g 2 times/day.Less than 15 ml/min1 g 1 time/day.Treatment of infections caused by Herpes simplex less than 15 ml/min500 mg 1 time/day.Treatment of labial herpes31-49 ml/min 1 g 2 times daily for 1 day15-30 ml/min 500 mg 2 times daily for 1 day less than 15 ml/min500 mg oncePrevention (suppression) of infections caused by Herpes simplex less than 15 ml/min when immunity is normal: 250 mg once daily for immunodeficiency: 500 mg once dailyTo reduce genital herpes infections less than 15 mL/min250 mg once daily
Patients on hemodialysis are recommended to receive valacyclovir immediately after completion of a hemodialysis session at a dose designed for patients with CK less than 15 mL/min. The drug should be used after the end of hemodialysis.
For prophylaxis of cytomegalovirus infection in adults and adolescents over 12 years old, the recommended dose is 2 g 4 times per day. The drug is prescribed as soon as possible after transplantation. The dose should be reduced depending on creatinine clearance (CK). Course duration is 90 days, but it may be increased in patients with high risk of infections.
Creatinine clearance (mL/min)Valacyclovir dose≥752 g 4 times/day.50 to < 751.5 g 4 times/day.25 to < 501.5 g 3 times/day.10 to < 251.5 g 2 times/day.< 10 or hemodialysis1.5 g 1 time/day.
Frequent CK monitoring is necessary, especially during periods when renal function changes rapidly (including immediately after transplantation or graft engraftment); the dose of valacyclovir should be adjusted according to CK.
Acyclovir is excreted primarily unchanged in the urine by active tubular secretion. Any drugs prescribed concomitantly with valacyclovir that have this excretion mechanism may increase the plasma concentration of acyclovir.
Cimetidine and probenecid increase the AUC of acyclovir by reducing its renal clearance, however, there is no need to adjust the dose due to the wide therapeutic index of acyclovir.
Precautions should be taken when prescribing high doses (4 g/day) of valacyclovir to prevent cytomegalovirus infection simultaneously with drugs that compete with acyclovir for excretion routes, because this may lead to elevated blood plasma levels of one or both drugs and their metabolites. Concomitant administration with mycophenolate mofetil increases plasma concentrations of acyclovir and the inactive metabolite of mycophenolate mofetil. Caution should also be exercised when concomitant administration of valacyclovir in high doses and other drugs that affect renal function (e.g., cyclosporine, tacrolimus).
Hydration. In elderly patients, persons with dehydration during treatment with Valacyclovir it is necessary to increase fluid intake. In the absence of significant renal dysfunction, dosing regimen adjustment is not required.
The use in patients with renal dysfunction and the elderly. Valacyclovir is excreted through the kidneys; in this regard, elderly patients with impaired renal function should reduce the dose of the drug. In patients with renal pathology in anamnesis the risk of nephrological complications increases, and such patients should be closely monitored for their timely detection.
The reduction of genital herpes virus transmission. Valacyclovir suppressive therapy reduces the risk of genital herpes transmission, but it does not cure herpes infection or completely eliminate the risk of transmission; avoidance of sexual intercourse is recommended.
The breastfeeding period. It is recommended with caution to prescribe valacyclovir to women during breastfeeding.
Impact on the ability to drive motor vehicles and other mechanisms. There are no special precautions.
In case of CNS side effects (including agitation, hallucinations, confusion, delirium, seizures and encephalopathy) the drug is discontinued.
- HIV infection with CD4+ lymphocytes less than 100/µl,
- childhood (under 12 years for CMV, under 18 years for other indications).
With caution. Hepatic/renal failure, elderly, hypohydration, concomitant use of nephrotoxic drugs, pregnancy, lactation, pediatric age.
Very often ≥1 in 10, often ≥1 in 100 and
Gastrointestinal disorders: often nausea, infrequently – abdominal pain, vomiting, diarrhea, rarely – increased activity of “liver enzymes” alanine aminotransferase (ALT), amputatinotransferase (AST), alkaline phosphatase (ALP), very rarely hepatitis.
With the blood and lymphatic system: very rarely – leukopenia, thrombocytopenia. Leukopenia is mainly found in patients with immunodeficiency.
Immune system disorders: very rarely – anaphylaxis.
Nervous system disorders: often – headache, rarely – dizziness, disorder and confusion, hallucinations, loss of consciousness; very rarely – agitation, tremor, ataxia, dysarthria, psychotic symptoms, convulsions, encephalopathy, coma.
These symptoms are mostly reversible and are seen mostly in patients with renal failure or other risk factors. In patients after organ transplantation who receive valacyclovir to prevent cytomegalovirus infection at high doses (8 g per day), neurological reactions occur more often than in those receiving lower doses.
Respiratory system and thoracic organs: infrequent – shortness of breath.
Hepatobiliary system: very rare – reversible increase in the level of functional liver tests, sometimes considered as hepatitis.
Skin and subcutaneous tissue disorders: infrequent – skin rashes, including photosensitization; rare – itching; very rare – urticaria, angioedema.
With the renal and urinary system: rare – renal dysfunction; very rare – acute renal failure.
Others: there are reports of renal failure, microangiopathy, hemolytic anemia and thrombocytopenia (sometimes in combination) in severe patients with immunodeficiency, especially in patients in the late stages of HIV infection who received high doses (8 g per day) of valacyclovir for a long time.
Occurrence of acute renal failure and neurological symptoms, including confusion, hallucinations, agitation, loss of consciousness and coma in patients with valacyclovir overdose, nausea and vomiting. Caution should be exercised when using the drug to prevent overdose. Many of the described cases of repeated overdose in patients with impaired renal function and in elderly patients were caused by insufficient reduction of the drug dose.
Patients should be closely monitored for timely diagnosis of toxic manifestations. Hemodialysis significantly accelerates excretion of acyclovir from the blood and may be considered the optimal treatment for symptomatic overdose.
There are limited data on the use of valacyclovir in pregnancy. Valacyclovir is used only when the potential benefit to the mother exceeds the possible risk to the fetus.
Recorded data on pregnancy outcomes in women who took valacyclovir or acyclovir, which is the active metabolite of valacyclovir, showed no increase in birth defects in their children compared to the general population. Because the registry included a small number of women who took valacyclovir in pregnancy, no reliable and definitive conclusions about the safety of valacyclovir in pregnancy can be drawn.
Acyclovir, the main metabolite of valacyclovir, is excreted with breast milk. After oral administration of valacyclovir at a dose of 500 mg, the Cmax of acyclovir in breast milk was 0.5-2.3 times (1.4 times on average) higher than the corresponding concentrations of acyclovir in maternal blood plasma. The area under the concentration-time curve (AUC) of acyclovir in breast milk versus the area under the concentration-time curve (AUC) of acyclovir in maternal plasma ranged from 1.4 to 2.6 (mean value 2.2). The mean concentration of acyclovir in breast milk was 2.24 µg/mL (9.95 µg/M). When the mother takes valacyclovir orally at a dose of 500 mg twice daily, the infant will be exposed to the same amount of acyclovir as when it is taken orally at a dose of about 0.61 mg/kg/day. The half-life (T1/2) of acyclovir from breast milk is the same as that from blood plasma. Valacyclovir in unchanged form was not detected in the mother’s plasma, breast milk or in the child’s urine.
In breastfeeding, the drug is used only if the estimated benefit to the mother exceeds the potential risk to the baby. With this in mind, caution should be exercised when prescribing valacyclovir to the mother during lactation (breastfeeding). However, intravenous (IV) administration of acyclovir at a dose of 30 mg/kg/day is used in infants to treat diseases caused by herpes simplex virus.
In experimental studies, valacyclovir had no teratogenic effect in rats and rabbits. Subcutaneous (p/k) administration of acyclovir in common teratogenicity tests did not cause teratogenic effects in rats and rabbits. In additional studies in rats, abnormalities in fetal development were detected when the drug was administered p/c in doses that increased the plasma concentration of acyclovir to 100 µg/ml and caused toxic effects in the mother.
When administered orally, valacyclovir caused no impairment of fertility in male and female rats.
Valtrex, Valacyclovir, Valcicon, Valvir, Valacyclovir Canon
|Conditions of storage|
At a temperature not exceeding 30 °C
Sun Pharmaceutical Industries Ltd, India
Sun Pharmaceutical Industries Ltd
Buy Vairova, 500 mg 10 pcs with delivery to USA, UK, Europe and over 120 other countries.