Valtrex, pills 500mg, 42pcs

Composition

Active ingredient:  

Valacicpovir hydrochloride 556 mg (equivalent to 500 mg of valacicpovir).

Auxiliary substances:  

Microcrystalline cellulose; 

Crospovidone;

Povidone K 90;

Magnesium stearate;

White dye concentrate;

Carnauba wax;

Printing ink; 

Diamond blue 5312 (FT 203).

Pharmacological action

Pharmacodynamics

 In humans, valacyclovir is rapidly and completely converted to acyclovir by the enzyme valacyclovir hydrolase. Acyclovir has in vitro specific inhibitory activity against herpes simplex viruses (HSV) types 1 and 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) 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 step of phosphorylation requires the activity of virus-specific enzymes. For HSV, VZV, and EBV, such an enzyme is viral thymidine kinase, which is present in virus-affected cells. Partial phosphorylation selectivity is preserved in cytomegalovirus and is mediated through the phosphotransferase gene product UL 97. Activation of acyclovir by a specific viral enzyme greatly explains 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 an obligate chain break, stopping DNA synthesis and, consequently, blocking viral replication.

In immunocompromised patients, HSV and VZV with reduced sensitivity to valacicpovir are extremely rare, but can sometimes be detected in patients with severe immune disorders, such as those with a bone marrow transplant, those receiving chemotherapy for malignancies, and those infected with HIV.

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

Pharmacokinetics

General information: After oral use, valacyclovir is well absorbed from the gastrointestinal tract, quickly and almost completely converting to acyclovir and valine. This transformation is catalyzed by the enzyme valacicpovirhydralase, isolated from the human liver. After a single dose of valaciclovir 250-2000 mg, the average peak plasma concentration of acyclovir in healthy volunteers with normal renal function is 10-37 mmol (2.2-8.3 mcg / ml), and the median time to reach this concentration is 1-2 hours. When taking valacicpovir at a dose of 1000 mg or more, the bioavailability of acyclovir is 54% and does not depend on food intake.

The peak concentration of valacicpovir in plasma is only 4% of the concentration of acyclovir, the median time to reach it is 30-100 minutes after taking the dose, after 3 hours the peak concentration level remains the same or decreases. Valacyclovir and acyclovir have similar pharmacokinetic parameters after oral use.

The degree of binding of valacicpovir to plasma proteins is very low (only 15%). In patients with normal renal function, the plasma half-life of acyclovir after valacyclovir use is about 3 hours, and in patients with end-stage renal failure, the average half-life is about 14 hours. Valacyclovir is excreted in the urine mainly in the form of acyclovir (more than 80% of the dose) and the acyclovir metabolite 9-carboxymethoxymethylguanine, and less than 1% of the drug is eliminated unchanged.

Patient characteristics: the pharmacokinetics of valacyclovir and acyclovir are largely unaffected in patients infected with PHi-VD viruses. In late pregnancy, a stable daily indicator of “area under the curve” (area under the curve of the plasma concentration/time ratio ) after taking 1000 mg of valacyclovir, it was approximately 2 times higher than that when taking acyclovir at a dose of 1200 mg per day. Taking Valtrex at a dose of 1000 mg or 2000 mg does not affect the disposition and pharmacokinetic parameters of valacyclovir in HIV-infected patients compared with healthy individuals.

In organ transplant recipients receiving valacyclovir 2000 mg 4 times a day, the peak concentration of acyclovir is equal to or exceeds that of healthy volunteers receiving the same dose of the drug, and their daily “area under the curve” indicators are significantly higher.

Indications

• Treatment of herpes zoster (shingles). Valtrex accelerates the disappearance of pain, reduces its duration and the percentage of patients with pain caused by shingles, including acute and postherpetic neuralgia.
• Treatment of skin and mucosal infections caused by HSV, including newly diagnosed and recurrent genital herpes.
• Treatment of labial herpes (labial fever).
• Valtrex is able to prevent the formation of lesions, if it is taken at the first symptoms of a relapse of herpes simplex.
• Prevention (suppression )of recurrent infections of the skin and mucous membranes caused by HSV, including genital herpes.
• Valtrex can reduce genital herpes infection in a healthy partner if taken as a suppressive therapy in combination with safe sex.
• Prevention of cytomegalovirus (CMV) infection that occurs during organ transplantation. Prophylactic use of Valtrex for CMV infection reduces the severity of acute graft rejection (in patients with kidney transplants), opportunistic infections and other herpesvirus infections (HSV, VZV).

Use during pregnancy and lactation

Teratogenicity: valacyclovir has no teratogenic effect in rats and rabbits. Valacyclovir is almost completely metabolized to acyclovir. Subcutaneous use of acyclovir in conventional teratogenicity tests did not cause teratogenic effects in rats and rabbits. In additional rat studies, fetal developmental disorders were detected with subcutaneous use of the drug in doses that caused an increase in the plasma concentration of acyclovir to 100 mcg / ml and toxic effects in the mother’s body.

Fertility: valacyclovir did not cause fertility problems in male and female rats when taken orally.

Pregnancy: There are insufficient data on the use of Valtrex during pregnancy. Valtrex should only be used during pregnancy if the potential benefit outweighs the potential risk. Data from pregnancy outcome records for women taking Valtrex or Zovirax (acyclovir is the active metabolite of valacyclovir) did not show an increase in the number of birth defects in their children compared to the general population. Since the register includes a small number of women who took valacyclovir during pregnancy, it is impossible to draw reliable and definite conclusions about the safety of valacyclovir during pregnancy.

Lactation: acyclovir, the main metabolite of valacyclovir, is excreted in breast milk. After use of valacyclovir at a dose of 500 mg orally, the maximum concentration of acyclovir (Cmax) in breast milk was 0.5-2.3 times (on average,1.4 times) higher than the corresponding concentrations of acyclovir in maternal plasma. The ratio of acyclovir AUC in breast milk to maternal plasma acyclovir AUC ranged from 1.4 to 2.6 ( mean 2.2).

The mean acyclovir concentration in breast milk was 2.24 mcg / ml (9.95 mcgM). When the mother takes valacyclovir 500 mg twice daily, the child will be exposed to the same effect of acyclovir as when taking it orally at a dose of about 0.61 mg / kg / day. The elimination half-life of acyclovir from breast milk is the same as from blood plasma. Valacyclovir unchanged was not detected in the mother’s plasma, breast milk, or urine of the child.

Valtrex should be administered with caution to nursing women. However, intravenous use of Zovirax at a dose of 30 mg / kg / day is used in newborns to treat diseases caused by the herpes simplex virus.

Contraindications

Valtrex is contraindicated in patients with hypersensitivity to valacicpovir, acicpovir and any auxiliary ingredient included in the Valtrex preparation.

It should be used with caution in clinically expressed forms of HIV infection.

Side effects

Adverse reactions are listed below according to the classification by major systems and organs and by frequency of occurrence. Frequency indicators used:

Very common: ≥ 1 in 10%^%Common: ≥ 1 in 100 or < 1 in 10; Uncommon: ≥ 1 in 1000 or%Rare: ≥ 1 in 10,000 or%Very rare:

Nervous system disorders often: headache.

Disorders of the gastrointestinal tract often: nausea. Post-marketing research data

Disorders of the blood and lymphatic system are very rare: leukopenia, thrombocytopenia. Leukopenia was mainly observed in patients with reduced immunity.

Immune system disorders are very rare: anaphylaxis.

Mental disorders and disorders of the nervous system Occasionally: dizziness, confusion, hallucinations, decreased mental abilities. Very rare: agitation, tremor, ataxia, dysarthria, psychotic symptoms, seizures, encephalopathy, coma.

The symptoms listed above are reversible and usually occur in patients with impaired renal function or other predisposing conditions. In patients with a transplanted organ receiving high doses (8 g per day) Valtrex for the prevention of CMV infection, neurological reactions develop more often than when taking lower doses.

Respiratory, thoracic and mediastinal disorders Often: dyspnoea

Gastrointestinal disorders Rare: abdominal discomfort, vomiting, diarrhea

Liver and biliary tract disorders Very rare: reversible violations of functional liver tests, which are sometimes regarded as manifestations of hepatitis.

Skin and subcutaneous tissue disorders Often: rashes, including photosensitivity reactions. Rare: itching. Very rare: urticaria, angioedema.

Disorders of the kidneys and urinary tract Rarely: impaired renal function. Very rare: acute renal failure, renal colic. (Renal colic may be associated with impaired renal function. ).

Other: Cases of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia (sometimes in combination) have been reported in patients with severe immune disorders, especially in patients with advanced AIDS who receive high doses of valacyclovir (8 g daily) for a long period of time. Similar complications were reported in patients with the same medical conditions, but not receiving valacyclovir.

Interaction

No clinically significant interactions have been established. Acyclovir is eliminated in the urine mainly in unchanged form, actively secreted into the renal tubules. After use of 1 g of Valtrex, cimetidine and probenecid, blocking tubular secretion, increase the AUC of acyclovir and reduce its renal clearance.

However, this dose of Valtrex does not require any correction due to the broad therapeutic index of acyclovir. Caution should be exercised in the case of concomitant use of Valtrex in higher doses (4 g per day) and drugs that compete with acyclovir for the elimination pathway, since there is a potential threat of increased plasma levels of one or both drugs or their metabolites.

An increase in the AUC of acyclovir and an inactive metabolite of mycophenolate mofetil, an immunosuppressive drug used in transplantation, was observed with simultaneous use of these drugs.

Caution should also be exercised (to monitor changes in renal function) when combining Valtrex in higher doses (4 g per day or more) with drugs that affect other renal functions (for example, cyclosporine, tacrolimus).

How to take, course of use and dosage

Treatment of herpes zoster

Adults

Valtrex is prescribed at a dose of 1000 mg 3 times a day for 7 days.

Treatment of HSV infections in adults Valtrex is prescribed at a dose of 500 mg 2 times a day.

In case of relapses, treatment should continue for 3 or 5 days. In more severe primary cases, treatment should be started as early as possible, and its duration should be increased from 5 to 10 days. In case of HSV relapses, Valtrex is considered ideal in the prodromal period or immediately after the first symptoms of the disease appear.

As an alternative for the treatment of labial herpes (labial fever), the use of Valtrex in a dose of 2 g twice within 1 day is effective. The second dose should be taken approximately 12 hours (but not earlier than 6 hours) after the first dose. When using this dosage regimen, the duration of treatment should not exceed 1 day, since this has not been shown to provide additional clinical benefits. Therapy should be initiated when the earliest symptoms of lip fever appear (i. e. tingling, itching, burning).

Prevention (suppression) of recurrent HSV infections

Adults

In patients with preserved immunity, Valtrex is prescribed at a dose of 500 mg once a day.

In patients with very frequent relapses (10 or more per year), an additional effect can be achieved by prescribing Valtrex in a daily dose of 500 mg, divided into 2 doses (250 mg 2 times a day).

For adult patients with immunodeficiency, the recommended dose of Valtrex is 500 mg 2 times a day. The duration of treatment is 4-12 months.

Prevention of genital herpes infection in a healthy partner.

Infected hete Rozexual adults with preserved immunity and with the number of exacerbations up to 9 per year, Valtrex should be taken 500 mg 1 time a day for a year or more every day with regular sexual activity, with irregular sexual contacts, Valtrex should be started 3 days before the intended sexual contact.

There are no data on the prevention of infection in other populations of patients.

Prevention of CMV infection

Doses for adults and adolescents (from 12 years of age)

It is recommended to prescribe Valtrex at a dose of 2 g 4 times a day, as early as possible, after transplantation.

The dose should be reduced depending on creatinine clearance.

The duration of treatment is 90 days, but in high-risk patients, treatment may be longer.

Doses for renal insufficiency: Treatment of shingles and HSV infections, prevention (suppression) and reduction of infection of a healthy partner: The dose of Valtrex is recommended to be reduced in patients with a significant decrease in renal function (see doses for renal insufficiency in the table).

Therapeutic indications

Herpes simplex prevention (suppression):

– immunocompromised patients less than 15,250 mg 1 time per day-immunocompromised patients less than 15,500 mg 1 time per day

Reduction of genital herpes infection less than 15 250 mg 1 time per day

Patients undergoing hemodialysis are recommended to use Valtrex immediately after the end of a hemodialysis session at the same dose as patients with a creatinine clearance of less than 15 ml / min.

CMV prevention:

The regimen of Valtrex use in patients with impaired renal function should be established in accordance with the data below.

• 75 and more than 2 g 4 times a day from 50 to less than
• 751.5 g 4 times a day from 25 to less than 501.5
• g 3 times a day from 10 to less than 251.5
• g 2 times a day less than 10 or dialysis*1.5 g 1 time a day.

In patients undergoing hemodialysis, Valtrex should be prescribed after the end of the hemodialysis session.

Creatinine clearance should be measured frequently, especially during periods when renal function changes rapidly, for example, immediately after transplantation or graft implantation, and the dose of Valtrex is adjusted according to creatinine clearance indicators.

Valtrex dose for impaired liver function

In patients with mild to moderate cirrhosis of the liver (synthetic liver function is preserved), no dose adjustment of Valtrex is required. Pharmacokinetic data in patients with severe cirrhosis of the liver (with a violation of synthetic liver function and the presence of shunts between the portal system and the general vascular bed) also do not indicate the need to adjust the dose of Valtrex, however, the experience of its clinical use in this pathology is limited.

Doses in children

There are no data on the use of Valtrex in children.

Doses in the elderly

No dose adjustment is required, except for a significant impairment of renal function. It is necessary to maintain an adequate water-electrolyte balance.

Overdose

Symptoms and signs:

Data on Valtrex overdose are insufficient. A single overdose of acyclovir up to 20 g, which was partially absorbed from the gastrointestinal tract, was not accompanied by a toxic effect of the drug. Oral use of ultrahigh doses of acyclovir for several days was associated with gastrointestinal (nausea and vomiting) and neurological symptoms (headache and confusion).

Overdoses of intravenous acyclovir are associated with increased serum creatinine levels and subsequent renal failure, with neurological complications including confusion, hallucinations, agitation, seizures, and coma.

Conduction:

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

Special instructions

Degree of hydration of the body: Adequate fluid replenishment should be provided in patients at risk of dehydration, especially in the elderly. Use in patients with renal insufficiency: the dose of Valtrex should be adjusted depending on the degree of impaired renal function. Patients with renal insufficiency have an increased risk of developing neurological complications.

Use of higher doses of Valtrex in patients with hepatic insufficiency and liver transplantation: there are no data on the use of Valtrex in higher doses (4 g or more per day)in patients with liver disease, so high doses of Valtrex should be prescribed with caution. Special studies on the effect of Valtrax in liver transplantation have not been conducted. However, high-dose prophylactic use of aceclavir has been shown to reduce CMV infection.

Use for genital herpes: Valtrex suppressive therapy reduces the risk of transmission of genital herpes, but does not completely eliminate it and does not lead to a complete cure. Valtrex therapy is recommended in combination with safe sex.

Influence on the ability to drive a car and mechanisms

No special precautions are required.

Form of production

Film-coated tablets

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Valacyclovir

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Children as prescribed by a doctor, Adults as prescribed by a doctor, Children over 12 years of age

Indications

Cytomegalovirus infection, Herpes