Valtrex

Active material: Valacyclovir
When ATH: J05AB11
CCF: Viricide
ICD-10 codes (testimony): A60, B00, B02, B02.2, B25
When CSF: 09.01.01
Manufacturer: GlaxoSmithKline Pharmaceuticals on (Poland)

Pharmaceutical form, composition and packaging

Pills, coated white, lenticular, oblong, without risk, on one side of the cyan ink affixed “VALTREX 500”; core tablet White or almost white.

Excipients: microcrystalline cellulose, krospovydon, povidone K90, magnesium stearate, silica colloidal anhydrous, carnauba wax, Concentrate white dye; printing inks, containing brilliant blue 5312 (FT203).

6 PC. – blisters (7) – packs cardboard.
10 PC. – blisters (1) – packs cardboard.

Pharmacological action

Viricide. In humans, valacyclovir is rapidly and completely converted to acyclovir under the influence valatsiklovirgidrolazy.

Ацикловир in vitro It has a specific inhibitory activity against Herpes simplex virus types 1 and 2, Varicella zoster и Эпштейна-Барра, cytomegalovirus and human herpes virus type 6. Acyclovir inhibits viral DNA synthesis immediately after phosphorylation and conversion to the active form of acyclovir triphosphate. The first stage of phosphorylation takes place with the participation of virus enzymes. For Herpes simplex virus, Varicella zoster and Epstein-Barr virus is such an enzyme thymidine kinase, which is present in virus-infected cells. Partial selectivity of phosphorylation retained by cytomegalovirus and mediated through the phosphotransferase gene product UL 97. Activation of acyclovir specific viral enzyme, to a great extent explains its selectivity.

Protsess fosforilirovaniya acyclovir (transformation from a mono- in triphosphate) ends cellular kinases. Acyclovir triphosphate competitive ingibiruet virusnuyu DNA and polimerazu, It is a nucleoside analogue, incorporated into the viral DNA, which leads to obligate (full) break circuit, cessation of DNA synthesis and, Consequently, to block replication of the virus.

Patients with immunocompetent viruses Herpes simplex Varicella zoster and with reduced sensitivity to extremely rare valacyclovir (less 0.1%), but sometimes it can be found in patients with severely impaired immunity, eg, with a bone marrow transplant, patients receiving chemotherapy for malignant tumors and in HIV-infected.

Resistance is caused by deficiency virus thymidine kinase, which leads to an excessive spread of the virus in the host organism. Sometimes decreased sensitivity to acyclovir due to the emergence of strains of the virus with the violation of the structure of the viral thymidine kinase or DNA polymerase. The virulence of the virus species resembles that of his wild strain.

Pharmacokinetics

Valacyclovir and acyclovir have similar pharmacokinetic parameters after oral administration.

Absorption

After oral administration valaciclovir is well absorbed from the gastrointestinal tract, rapidly and almost completely converted to acyclovir and valine. This conversion is catalyzed by the enzyme valatsiklovirgidrolazoy, isolated from human liver.

After a single dose 0.25-2 г валацикловира C_max acyclovir in healthy volunteers with normal renal function averages 10-37 mmol (2.2-8.3 ug / ml), and the median time to achieve this concentration 1-2 no.

When receiving a dosage of valacyclovir 1 g bioavailability of acyclovir is 54% and independent of food intake.

C_max Valaciclovir in the plasma is only 4% and the concentration of acyclovir is achieved at a mean 30-100 minutes after administration; through 3 h Level C_max It remains the same or decreases.

Distribution

The degree of binding of acyclovir to plasma proteins is very low – 15%.

Deduction

In patients with normal renal function T_1/2 Acyclovir is about 3 no. Valacyclovir is excreted in urine, mainly in the form of acyclovir (more 80% dose) and ego metabolite 9-karboksimetoksimetilguanina, unchanged output less 1% product.

Pharmacokinetics in special clinical situations

In patients with end-stage renal failure T_1/2 Acyclovir is about 14 no.

Pharmacokinetics of the acyclovir and valaciclovir largely disturbed patients, infected with Herpes simplex virus and Varicella zoster.

In later pregnancy, a stable daily the AUC after administration 1 g valaciclovir was bigger around 2 times, than that when taking a dose of acyclovir 1.2 g / day.

Receiving a dose of Valtrex 1 and g 2 g does not violate the distribution and pharmacokinetic parameters of valaciclovir in HIV-infected patients compared to healthy individuals.

In recipients of organ transplants, receiving valaciclovir dose 2 g 4 times / day, C_max Acyclovir is equal to or exceeds that in healthy volunteers, receive the same dose, and the daily AUC in these indicators are much higher.

Testimony

- The treatment of herpes zoster, caused by the virus Varicella zoster (It accelerates the disappearance of pain, it reduces the duration and percentage of patients with pain, including acute and postherpetic neuralgia);

- Treatment of infections of the skin and mucous membranes, caused by the Herpes simplex virus type 1 and 2 (including newly diagnosed and recurrent genital herpes);

- Treatment of herpes labialis (Lip fever);

- Valtrex is able to prevent the formation of lesions, if taken at the first symptoms of recurrent herpes simplex;

- Prevention (supressiya) recurrence of diseases of the skin and mucous membranes, caused by the Herpes simplex virus type 1 and 2, including genital herpes;

- Valtrex can reduce genital herpes infection of the healthy partner, if taken as a suppressive therapy in combination with safer sex;

- Prevention of cytomegalovirus infection, occurring in organ transplantation (reduces the severity of the reaction of acute transplant rejection in patients with kidney transplants, develop opportunistic infections and other viral infections, caused by the Herpes simplex virus and Varicella zoster).

Dosage regimen

To the treatment of herpes zoster adult appoint 1 g 3 times / day for 7 days.

To treatment of diseases, caused by the Herpes simplex virus, adult Valtrex is prescribed 500 mg 2 times / day. In the case of relapse, treatment should be performed for 3 or 5 days. In more severe cases, the primary treatment should be started as early as possible, and its duration should be increased 5 to 10 days. In recurrent disease is considered optimal assignment of Valtrex in the prodromal period or immediately after onset of symptoms.

As an alternative for treating labial herpes (lip fever) effective dose of Valtrex appointment 2 g 2 times during 1 day. The second dose should be taken approximately 12 no (but not earlier, than 6 no) after the first dose. With this dosing regimen, the duration of treatment should not exceed 1 day, because no additional clinical benefit gives. Therapy should begin with the appearance of the earliest symptoms of fever lip (ie. tingle, itch, burning).

To prevention (supressii) recurrence of infections, caused by the Herpes simplex virus, adults with normal parameters of immunity administered at a dose of 500 mg 1 time / day. At very frequent relapses (10 and more than once a year) It may be more effective appointment at a daily dose of Valtrex 500 mg, razdelennoy of 2 admission (by 250 mg 2 times / day). Adults with immunodeficiency It is encouraged to nominate for 500 mg 2 times / day.

Duration of treatment – 4-12 Months.

To prevention of infection with genital herpes healthy partner in heterosexual adult immunocompetent patients with and up to the number of exacerbations 9 year Valtrex should be used for 500 mg 1 time / day for a year and more every day with regular sexual intercourse, at irregular sexual contacts should begin receiving Valtrex for 3 the day before the alleged sexual contact.

Data on the prevention of infection in other populations of patients with no.

To the prevention of cytomegalovirus infection in Adults and adolescents older 12 years The recommended dose is at 2 g 4 times / day. The drug is administered as soon as possible after transplantation. The dose should be reduced depending on the spacecraft. The duration of the course is 90 days, but may be increased in patients with a high risk of infection.

At renal failure dosing regimen is adjusted to the clearance of creatinine and readings.

Patients, hemodialysis, Valtrex is recommended to appoint immediately after the end of hemodialysis at a dose, designed for patients with CC less than 15 ml / min. The drug should be used after the end of hemodialysis.

To prevention of cytomegalovirus infections Valtrex is recommended to be administered in the following doses.

Patients, hemodialysis, Valtrex should be administered after hemodialysis.

Requires frequent monitoring QC, especially at a time, when renal function is changing rapidly (incl. immediately after transplantation or engraftment); Valtrex dose should be adjusted in accordance with CC.

Side effect

Adverse reactions listed below in accordance with the classification on the main organs and systems and in the incidence of: Often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10 000, <1/1000), rarely (<10 000).

CNS: often – headache.

From the digestive system: often – nausea.

These post-marketing studies

CNS: rarely – dizziness, confusion, hallucinations, mental decline; rarely – excitation, tremor, ataxia, dysarthria, psychotic symptoms, convulsions, encephalopathy, coma.

These reactions are reversible and usually seen in patients with impaired renal function or in comparison with other predisposing conditions. Patients with organ transplant, receiving high doses of Valtrex (8 g / day) for the prevention of cytomegalovirus infection, neurological reactions occur more frequently, than when lower doses.

The respiratory system: infrequently – dyspnoea.

From the digestive system: rarely – abdominal discomfort, vomiting, diarrhea; rarely – reversible disturbances of liver function tests (which is sometimes regarded as a manifestation of hepatitis).

From the hematopoietic system: rarely – leukopenia (mainly observed in patients with reduced immunity), thrombocytopenia.

Dermatological reactions: infrequently – rash, manifestations of photosensitivity; rarely – itch.

Allergic reactions: rarely – hives, angioedema, anaphylaxis.

From the urinary system: rarely – renal dysfunction; rarely – acute renal failure, počečnaâ how (It may be associated with impaired renal function).

Other: in patients with severely impaired immunity, especially in the later stages of AIDS, receiving high doses of valaciclovir (8 g / day every day) for a long time, there have been cases of renal failure, microangiopathic hemolytic anemia and thrombocytopenia (sometimes in combination). Similar side reactions have been observed in patients with the same disease, but not receiving valacyclovir.

Contraindications

- Hypersensitivity to valacyclovir, acyclovir and any other component, part of the drug.

FROM caution should be used for symptomatic forms of HIV.

Pregnancy and lactation

There are limited data on the use of Valtrex in pregnancy. Valtrex is used only in cases, the potential benefit to the mother outweighs the potential risk to the fetus.

Recorded data on the outcome of pregnancy in women, taking Valtrex or Zovirax (Acyclovir is an active metabolite of valaciclovir), They showed no increase in the number of birth defects in their children compared with the general population. Since the register including a small number of women, taking valacyclovir during pregnancy, the authentic and definite conclusions on the safety of valaciclovir in pregnancy can not be done.

Acyclovir, the major metabolite of valaciclovir, excreted in breast milk. After receiving valaciclovir oral dose 500 mg C_max acyclovir in breast milk 0.5-2.3 times (on average 1.4 times) higher than the corresponding concentrations of acyclovir in the plasma of the mother's blood. Отношение AUC ацикловира, present in breast milk to the AUC of acyclovir in plasma ranged from mother 1.4 to 2.6 (average value 2.2). Mean concentrations of acyclovir in the breast milk was 2.24 ug / ml (9.95 ug / M). When receiving mother valaciclovir oral dose 500 mg 2 times / day a child will undergo the same effects of acyclovir, it when receiving an oral dose of about 0.61 mg / kg / day. T_1/2 acyclovir from breast milk is the same, both from plasma. Valacyclovir in unchanged form was not detected in maternal plasma, breast milk or baby urine.

Considering this, should be used with caution Valtrex mother during lactation (breast-feeding). However, in / in a dose of Zovirax 30 mg / kg / day used for the treatment of neonatal diseases, herpes simplex virus.

IN experimental studies valacyclovir not teratogenic in rats and rabbits. P / to the introduction of aciclovir in standard tests for teratogenicity caused no teratogenic effects in rats and rabbits. In additional studies in rats fetal malformations were detected at n / to the introduction of the drug in doses, which induced an increase in the plasma concentration of acyclovir to 100 ug / mL and the toxic effects in the mother.

When oral valacyclovir did not induce fertility disorders in male and female rats.

Cautions

Patients at risk of dehydration, especially elderly patients, during treatment Valtrex is necessary to ensure adequate hydration of the body.

In patients with renal impairment have an increased risk of developing neurological complications.

If abnormal liver function in patients with mild to moderate hepatic cirrhosis (synthetic liver function is preserved) Valtrex dose adjustment is not required. In the study of the pharmacokinetics in patients with severe liver cirrhosis (in violation of the synthetic function of the liver and the presence of shunts between the portal system and a common vascular bed) also no evidence, evidence of the need to correct dosing regimen; However, clinical experience with the drug Valtrex in this category of patients is organic.

There are no data on the use of Valtrex in high doses (4 g / day or more) in patients with liver diseases, therefore, caution should be prescribed the drug in high doses for these patients.

Elderly patients dose adjustment is required, except in cases of significant renal dysfunction. It is necessary to maintain an adequate fluid and electrolyte balance.

Special studies on the effect of Valtrex in patients undergoing liver transplant was conducted. However, it was shown, that prophylactic acyclovir in high doses reduces cytomegalovirus infection.

Suppressive therapy with Valtrex reduces the risk of transmission of genital herpes, but it does not eliminate it completely and does not lead to complete cure. During therapy, Valtrex patient should take measures to ensure the security of the partner during sexual intercourse.

Use in Pediatrics

Experience of clinical application of the drug in children missing.

Effects on ability to drive and operate machinery

Special precautions are not required.

Overdose

Currently, data on overdose of Valtrex is not enough.

Symptoms: after a single ingestion of excessive dose of acyclovir up 20 g is a partial absorption from the gastrointestinal tract, it was not accompanied by toxic effects of the drug. Ingestion of acyclovir in excessive doses over several days accompanied by gastrointestinal (nausea, vomiting) and neurological symptoms (headache, confusion). In / in the introduction of acyclovir in excessive doses, accompanied by an increase in serum creatinine and subsequent development of renal failure, while neurological complications included confusion, hallucinations, excitation, convulsions and who.

Treatment: patients should be under close medical observation for signs of toxic action. Haemodialysis significantly enhances the removal of aciclovir from the blood and can be considered the method of choice in the management of patients with an overdose of Valtrex.

Drug Interactions

Clinically significant interaction Valtrex with other drugs is not installed.

Acyclovir is excreted in the urine mainly as unchanged as a result of active tubular secretion. Upon receiving a dose Valtrex 1 d cimetidine and probenecid, that block tubular secretion, acyclovir increased AUC and decrease its renal clearance. However Valtrex dose correction is not required, tk. Acyclovir has a wide therapeutic index.

It should be used with caution Valtrex in higher doses (4 g / day) simultaneously with drugs, which compete with aciclovir for elimination pathway, tk. there is the risk of increasing the blood plasma level of one or both drugs or their metabolites. Bыlo otmecheno povыshenie AUC acyclovir and neaktivnogo metabolite mycophenolic mofetil (immunosuppressant, used in transplantation) while the application of these drugs.

Care must be taken with a combination high-dose Valtrex (4 g / day and above) with drugs, violating kidney function (incl. cyclosporine, tacrolimus).

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored at temperatures not above 30 ° C out of reach of children. Shelf life – 3 year.