Valtrex, 500 mg 10 pcs

Pharmgroup:

an antiviral drug.

Pharmic action:

Valtrex is an antiviral drug. In the human body valacyclovir is quickly and completely converted to acyclovir by valacyclovirhydrolase.

Aciclovir in vitro has specific inhibitory activity against Herpes simplex viruses types 1 and 2, Varicella zoster and Epstein-Barr, cytomegalovirus and human herpes virus type 6.

Aciclovir inhibits the synthesis of viral DNA immediately after phosphorylation and transformation into the active form acyclovir triphosphate. The first stage of phosphorylation occurs with the participation of virus-specific enzymes. For Herpes simplex, Varicella zoster and Epstein-Barr viruses, this enzyme is viral thymidine kinase, which is present in virus-affected cells. Partial phosphorylation selectivity is retained in cytomegalovirus and is mediated through the phosphotransferase gene product UL 97. Activation of acyclovir by a specific viral enzyme explains much of its selectivity.

The process of phosphorylation of acyclovir (conversion from mono- to triphosphate) is completed by cellular kinases. Acyclovir triphosphate competitively inhibits viral DNA polymerase and, being a nucleoside analog, is incorporated into viral DNA, which leads to obligate (complete) chain breaking, termination of DNA synthesis and, consequently, to blocking of virus replication.

In immunocompromised patients, Herpes simplex and Varicella zoster viruses with hypersensitivity to Valacyclovir are extremely rare (less than 0.1%), but can sometimes be found in patients with severe immune disorders, such as bone marrow transplants, those receiving chemotherapy for malignancies and those with HIV.

Resistance is caused by a thymidine kinase deficiency in the virus, which leads to excessive spread of the virus in the host. Sometimes decreased sensitivity to acyclovir is due to the emergence of virus strains with disrupted viral thymidine kinase or DNA polymerase structure. The virulence of these varieties of the virus is similar to that of its wild strain.

Pharmacokinetics:

Valacyclovir and acyclovir have similar pharmacokinetic parameters after oral administration.

absorption

Valacyclovir is well absorbed from the gastrointestinal tract after oral administration and is rapidly and almost completely converted to acyclovir and valine. This conversion is catalyzed by the enzyme valacyclovirhydrolase isolated from human liver.

After a single dose of 0.25-2 g of valacyclovir, the Cmax of acyclovir in healthy volunteers with normal renal function averages 10-37 µmol (2.2-8.3 µg/mL) and the median time to reach this concentration is 1-2 hours.

The bioavailability of acyclovir is 54% when valacyclovir is taken at a dose of 1 g or more and is not dependent on food intake.

The Cmax of valacyclovir in plasma is only 4% of the acyclovir concentration and is reached on average 30-100 min after taking the drug; after 3 h the Cmax level remains the same or decreases.

Distribution

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

Elimation

In patients with normal renal function the T1/2 of acyclovir is about 3 hours. Valacyclovir is excreted with the urine, mainly as acyclovir (more than 80% of the dose) and its metabolite 9-carboxymethoxymethylguanine, less than 1% of the drug is excreted unchanged.
Pharmacokinetics in special clinical cases

In patients with terminal renal failure the T1/2 of acyclovir is approximately 14 hours.

The pharmacokinetics of valacyclovir and acyclovir are not significantly impaired in patients infected with Herpes simplex and Varicella zoster viruses.

In late pregnancy, the sustained daily AUC after administration of 1 g of valacyclovir was approximately 2 times greater than that of acyclovir at a dose of 1.2 g/day.

The administration of Valtrex in doses of 1 g and 2 g does not impair the distribution and pharmacokinetic parameters of valacyclovir in HIV-infected patients compared to healthy individuals.

In organ transplant recipients receiving Valacyclovir at a dose of 2 g 4 times daily, the Cmax of acyclovir is equal to or greater than that of healthy volunteers receiving the same dose of the drug, and their daily AUCs are significantly higher.

Indications

– treatment of herpes zoster caused by Varicella zoster virus (accelerates the disappearance of pain, reduces its duration and the percentage of patients with pain, including acute and post-herpetic neuralgia);
– Treatment of infections of the skin and mucous membranes caused by Herpes simplex virus types 1 and 2 (including newly detected and recurrent genital herpes);
– Treatment of labial herpes (lip fever);
– Valtrex can prevent lesions if taken at the first symptoms of herpes simplex relapse;
– Prevention (suppression) of relapses of skin and mucous membrane diseases caused by Herpes simplex virus types 1 and 2, including genital herpes;
– Valtrex can reduce genital herpes infection of a healthy partner if it is taken as suppressive therapy in conjunction with safe sex;
– prevention of cytomegalovirus infection occurring in organ transplantation (reduces the severity of acute transplant rejection reactions in patients with kidney transplants, the development of opportunistic infections and other viral infections caused by Herpes simplex and Varicella zoster viruses).

Active ingredient

Composition

How to take, the dosage

Ingestion. Adults with herpes zoster – 1000 mg 3 times a day (7 days).

In herpes simplex – 500 mg 2 times a day; in relapses – for 5 days.

In the first episode with a severe course, the duration of treatment may be increased to 10 days.

Interaction

Clinically significant interaction of Valtrex with other medicinal products has not been established.

Aciclovir is excreted in the urine mainly unchanged as a result of active tubular secretion. After Valtrex administration at a dose of 1 g, cimetidine and probenecid, which block tubular secretion, increase the AUC of acyclovir and decrease its renal clearance. However, there is no need to adjust the dose of Valtrex in this case, since acyclovir has a wide therapeutic index.

We should use Valtrex with caution at higher doses (4 g/day) concomitantly with drugs that compete with acyclovir for the elimination pathway, since there is a risk of elevated plasma levels of one or both drugs or their metabolites.

The AUC of acyclovir and the inactive metabolite of mycophenolate mofetil (an immunosuppressant used in transplantation) have been observed to increase with concomitant use of these drugs.

Caution should be exercised when combining Valtrex in high dose (4 g/day or more) with drugs that impair renal function (including cyclosporine, tacrolimus).

Special Instructions

Patients at risk of dehydration, especially elderly patients, should be adequately hydrated during treatment with Valtrex.

Patients with renal insufficiency have an increased risk of neurological complications.

In patients with mild to moderate hepatic cirrhosis (synthetic liver function is preserved), there is no need to adjust the dose of Valtrex in patients with hepatic impairment. In pharmacokinetic studies in patients with severe cirrhosis (with impaired hepatic synthetic function and the presence of shunts between the portal system and the common vascular system) there is also no data to indicate the need for dosage adjustment; however, clinical experience with Valtrex in this category of patients is limited.

There are no data on the use of Valtrex at high doses (4 g/day or more) in patients with liver disease; therefore, caution should be exercised when prescribing Valtrex at high doses in this patient population.

Patients in the elderly do not require dose adjustment except in cases of significant renal impairment. Adequate water-electrolyte balance should be maintained.

Special studies to study the effect of Valtrex in patients with liver transplantation have not been conducted. However, prophylactic administration of acyclovir at high doses has been shown to reduce cytomegalovirus infection.

Valtrex suppressive therapy reduces the risk of genital herpes transmission, but it does not eliminate it completely and does not lead to a complete cure. During therapy with Valtrex, patients should take steps to ensure their partner’s safety during sexual intercourse.

Pediatric use

There is no clinical experience with Valtrex in children.

Impact on ability to drive and operate machinery
No special precautions are required.

Contraindications

Side effects

The adverse reactions are listed below according to the classification by major systems and organs and by frequency of occurrence: very common (≥1/10), common (≥1/100, CNS: common – headache.

Digestive system disorders: often – nausea.
Post-marketing study data

Immune system disorders: very rare – anaphylaxis.

CNS disorders: rarely – dizziness, confusion, hallucinations, decreased mental capacity; very rarely – agitation, tremor, ataxia, dysarthria, psychotic symptoms, seizures, encephalopathy, coma.

The above reactions are reversible and are usually seen in patients with impaired renal function or with other predisposing conditions. In patients with an organ transplant who receive Valtrex in high doses (8 g/day) to prevent cytomegalovirus infection, neurological reactions develop more often than when taken in lower doses.

Respiratory system disorders: infrequent – dyspnea.

The digestive system: rare – abdominal discomfort, vomiting, diarrhea; very rare – reversible disorders of liver function tests (which are sometimes regarded as manifestations of hepatitis).

Hematological reactions: very rarely – leukopenia (especially in patients with lowered immunity), thrombocytopenia.
Dermatological reactions: infrequent – rash, manifestations of photosensitivity; rarely – itching.

Allergic reactions: very rare – urticaria, angioedema.

The urinary system: rare – renal dysfunction; very rare – acute renal failure, renal colic (may be associated with renal dysfunction).

Others: in patients with severe immune disorders, especially in the late stage of AIDS, receiving valacyclovir in high doses (8 g/day daily) for a long time, cases of renal failure, microangiopathic hemolytic anemia and thrombocytopenia (sometimes in combination) were observed. Similar adverse reactions have been reported in patients with the same disease but not receiving valacyclovir.

Overdose

There are currently insufficient data on Valtrex overdose.

Symptoms:In a single oral overdose of acyclovir up to 20 g, there was partial absorption from the gastrointestinal tract, which was not accompanied by toxic effects of the drug.

Ingestion of acyclovir in excessive doses for several days was accompanied by gastrointestinal (nausea, vomiting) and neurological symptoms (headache, confusion). Injection of acyclovir in excessive doses was accompanied by an increase in serum creatinine levels and subsequent development of renal failure, with neurological complications including confusion, hallucinations, agitation, seizures and coma.

Treatment:Patients should be closely monitored medically for signs of toxic effects. Hemodialysis significantly enhances the removal of acyclovir from the blood and may be considered the method of choice in the management of patients with Valtrex overdose.

Pregnancy use

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

Caution is advised when prescribing Valtrex during lactation.

Similarities