Instructions for Valtrex (valaciclovir)
Dosage form:
The tablets, film-coated in white, are oblong, biconvex, without risks, the inscription "GX CF1" is engraved on one side; tablet core from white to almost white.
Structure:
1 tab
valaciclovir hydrochloride 556 mg,
which corresponds to the content of valaciclovir 500 mg
Excipients: microcrystalline cellulose - 70 mg, crospovidone - 28 mg, povidone K90 - 22 mg, magnesium stearate - 4 mg, colloidal silicon dioxide - 2 mg.
The composition of the film membrane: white opadray ~ 14 mg (hypromellose - 9.48 mg, titanium dioxide - 3.26 mg, macrogol 400 - 1.12 mg, polysorbate 80 - 0.14 mg); polishing (carnauba wax ~ 0.016 mg).
General description:
Antiviral drug
Special conditions:
Patients at risk of dehydration, especially elderly patients, should be provided with adequate hydration during treatment with Valtrex.
Patients with renal failure have an increased risk of developing neurological complications.
In cases of impaired liver function in patients with mild or moderate hepatic cirrhosis (synthetic liver function is preserved), dose adjustment of Valtrex is not required.
In the study of pharmacokinetics in patients with severe cirrhosis of the liver (with impaired synthetic liver function and the presence of shunts between the portal system and the common vascular bed), no data were obtained indicating the need for correction of the dosage regimen; however, the clinical experience with Valtrex in this category of patients is organic.
There are no data on the use of Valtrex in high doses (4 g / or more) in patients with liver diseases, therefore, it is necessary to carefully prescribe the drug in high doses of this category of patients.
Elderly patients do not need dose adjustment, except in cases of significant renal impairment. An adequate water-electrolyte balance must be maintained.
Special studies to study the effect of Valtrex in patients with liver transplantation have not been conducted. However, it has been shown that prophylactic administration of acyclovir in high doses reduces cytomegalovirus infection.
Suppressive therapy with Valtrex reduces the risk of transmitting genital herpes, but does not completely exclude it and does not lead to a complete cure. During Valtrex therapy, the patient should take measures to ensure the safety of the partner during sexual intercourse.
Pediatric Use
There is no experience with the clinical use of the drug in children.
Influence on the ability to drive vehicles and work with mechanisms
No special precautions are required.
Drug interaction:
- Hypersensitivity to valaciclovir, acyclovir and any other component that is part of the drug.
Caution should be used in clinically expressed forms of HIV infection.
Pharmacodynamics:
Antiviral drug. In the human body, valaciclovir is rapidly and completely converted to acyclovir under the influence of valacyclovir hydrolase.
In vitro acyclovir has specific inhibitory activity against Herpes simplex viruses types 1 and 2, Varicella zoster and Epstein-Barr, cytomegalovirus and human herpes virus type 6. Acyclovir inhibits the synthesis of viral DNA immediately after phosphorylation and transformation into an active form of 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-infected cells. Partial selectivity of phosphorylation is retained in cytomegalovirus and is mediated through the product of the phosphotransferase gene UL 97. Activation of acyclovir by a specific viral enzyme to a large extent explains its selectivity.
The process of acyclovir phosphorylation (conversion from mono-to triphosphate) is completed by cell kinases. Acyclovir triphosphate competitively inhibits viral DNA polymerase and, being an analog of a nucleoside, integrates into viral DNA, which leads to obligate (complete) breaking of the chain, termination of DNA synthesis and, therefore, to block replication of the virus.
In patients with preserved immunity, Herpes simplex and Varicella zoster viruses with reduced sensitivity to valaciclovir are extremely rare (less than 0.1%), but can sometimes be found in patients with severe immune disorders, for example, bone marrow transplant, in patients receiving chemotherapy for malignant neoplasms and in HIV-infected people.
Resistance is caused by a deficiency of the thymidine kinase of the virus, which leads to an 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 resembles that of its wild strain.
Pharmokinetics:
Valaciclovir and acyclovir have similar pharmacokinetic parameters after oral administration.
Suction
After oral administration, valaciclovir is well absorbed from the digestive tract, quickly and almost completely turns into acyclovir and valine. This transformation is catalyzed by the enzyme valaciclovir hydrolase isolated from the human liver.
After a single dose of 0.25-2 g of valaciclovir, Cmax of acyclovir in healthy volunteers with normal renal function is on average 10-37 μmol (2.2-8.3 μg / ml), and the median time to reach this concentration is 1-2 hours.
When taking valaciclovir in a dose of 1 g, the bioavailability of acyclovir is 54% and does not depend on food intake.
Cmax of valaciclovir in plasma is only 4% of the concentration of acyclovir and is achieved on average 30-100 minutes after taking the drug; after 3 hours, the Cmax level remains the same or decreases.
Distribution
The degree of binding of acyclovir to plasma proteins is very low - 15%.
Breeding
In patients with normal renal function, T1 / 2 of acyclovir is approximately 3 hours. Valacyclovir is excreted in the urine, mainly in the form of 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 end-stage renal failure, T1 / 2 of acyclovir is approximately 14 hours.
The pharmacokinetics of valaciclovir and acyclovir are not significantly impaired in patients infected with Herpes simplex and Varicella zoster viruses.
In late pregnancy, the steady daily AUC after taking 1 g of valaciclovir was approximately 2 times greater than that when taking acyclovir at a dose of 1.2 g /
Taking Valtrex at a dose of 1 g and 2 g does not violate the distribution and pharmacokinetic parameters of valaciclovir in HIV-infected patients compared with healthy individuals.
In organ transplant recipients receiving 2 g of valaciclovir, Cmax of acyclovir is equal to or superior to that of healthy volunteers receiving the same dose of the drug, and their daily AUC is much higher.
Indications:
- treatment of herpes zoster caused by the Varicella zoster virus (accelerates the disappearance of pain, reduces its duration and the 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 the first detected and recurrent genital herpes);
- treatment of labial herpes (lip fever);
- is able to prevent the formation of lesions if it is taken when the first symptoms of herpes simplex relapse appear;
- prevention (suppression) of relapses of skin and mucous membrane diseases caused by Herpes simplex virus type 1 and 2, including genital herpes;
- can reduce the infection of a healthy partner with genital herpes if it is taken as suppressive therapy in combination with safe sex;
Contraindications:
- Hypersensitivity to valaciclovir, acyclovir and any other component that is part of the drug.
Caution should be used in clinically expressed forms of HIV infection.
Overdose
with a single oral administration of acyclovir in an excessive dose of up to 20 g, partial absorption from the gastrointestinal tract occurred, which was not accompanied by the toxic effect of the drug. Ingestion of acyclovir in excessive doses for several days was accompanied by gastrointestinal (nausea, vomiting) and neurological
Side effects:
From the digestive system: often - nausea.
Post-Marketing Research Data
On the part of the immune system: very rarely - anaphylaxis.
From the side of the central nervous system: rarely - dizziness, confusion, hallucinations, decreased mental ability; very rarely - agitation, tremor, ataxia, dysarthria, psychotic symptoms, convulsions, encephalopathy, coma.
These reactions are reversible and usually observed in patients with impaired renal function or against the background of other predisposing conditions. In patients with a transplanted organ receiving Valtrex in high doses (8 g /) for the prevention of cytomegalovirus infection, neurological reactions develop more often than when taken in lower doses.
From the respiratory system: infrequently - dyspnea.
From the digestive system: rarely - a feeling of discomfort in the abdomen, vomiting, diarrhea; very rarely, reversible violations of liver function tests (which are sometimes regarded as manifestations of hepatitis).
From the hemopoietic system: very rarely - leukopenia (mainly observed in patients with reduced immunity), thrombocytopenia.
Dermatological reactions: infrequently - rash, photosensitivity manifestations; rarely itching.
Allergic reactions: very rarely - urticaria, angioedema.
From the urinary system: rarely - impaired renal function; very rarely - acute renal failure, renal colic (may be associated with impaired renal function)
Ways of application:
For the treatment of herpes zoster, adults are prescribed 1 g 3 for 7 days.
For the treatment of diseases caused by the Herpes simplex virus, adults of Valtrex are prescribed 500 mg 2. In case of relapse, treatment should be carried out within 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. With relapses of the disease, the appointment of Valtrex in the prodromal period or immediately after the onset of the first symptoms of the disease is considered optimal.
As an alternative to the treatment of labial herpes (labial fever), it is effective to administer Valtrex 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 taking the first dose. With this dosing regimen, the duration of treatment should not exceed 1 day, since it does not provide additional clinical benefits. Therapy should be started when the earliest symptoms of lip fever appear (i.e., tingling, itching, burning).
For the prevention (suppression) of relapse of infections caused by Herpes simplex virus, adults with normal immunity are prescribed at a dose of 500 mg 1 time / Adults with immunodeficiency are recommended to be prescribed 500 mg 2
The duration of treatment is 4-12 months.
For the prevention of infection of a healthy partner with genital herpes in heterosexual adult patients with preserved immunity and with the number of exacerbations up to 9 per year, Valtrex should be prescribed 500 mg 1 time / year or more every day with regular sexual contacts, with irregular sexual contacts, Valtrex is necessary start 3 days before the alleged sexual intercourse.
Data on the prevention of infection in other patient populations are not available.
For the prevention of cytomegalovirus infection in adults and adolescents over 12 years of age, the recommended dose is 2 g 4. The drug is prescribed as soon as possible after transplantation. The dose should be reduced depending on the QC. The duration of the course is 90 days, but can be increased in patients with a high risk of developing infections.
In renal failure, the dosage regimen is set depending on the creatinine clearance and indications.
