Valtrovir

An antiviral drug with the active ingredient valacyclovir hydrochloride, which inhibits the activity of the enzyme DNA polymerase, a catalyst for the synthesis of polymers of nucleic acids of herpes viruses.

Indications Valtrovir

Herpetic lesions of the skin and mucous membranes, both detected for the first time and relapses of the disease. It is used in the therapy of viral lesions of various types and localizations - on the lips, genitals, shingles.

For preventive purposes, to reduce the likelihood of infection during safe sexual intercourse, the drug is used as a therapy that suppresses viral activity.

To prevent the development of CMV-associated infection in recipients of donor organs.

Release form

It is produced in film-coated tablet form, each unit of the drug contains 0.5 g of valacyclovir hydrochloride.

Pharmacodynamics

The active substance of Valtrovir inhibits the enzymatic activity of viral DNA polymerase, the inactivity of which interrupts the production of viral nucleic acids and stops the reproduction and development of the microorganism. In laboratory conditions, alcyclovir exhibits antiviral activity against the following types: HSV-1, HSV-2 (simple herpes types I and II), VZV (chickenpox), CMV (cytomegalovirus), Epstein-Barr, HHV-6 (human herpes type VI).

When entering the human body, valacyclovir hydrochloride is hydrolyzed at a good rate and almost completely with the formation of acyclovir. The catalyst for hydrolysis is the liver mitochondrial enzyme (valaciclovir hydrolase).

After which acyclovir accumulates in the cells affected by the herpes virus. Viral thymidine kinase stimulates the onset of phosphorylation reactions with the formation of acyclovir monophosphate, cellular kinases catalyze the following reactions, as a result - active acyclovir triphosphate is formed, suppressing the genomic replication of herpesvirus deoxyribonuclease.

In case of cytomegalovirus infection, the conversion to acyclovir triphosphate is catalyzed by phosphotransferase UL 97. In both cases, the enzymes of the viral cells complete the formation of acyclovir triphosphate, which, competing with the natural nucleoside, is included in the synthesized chain of viral DNA and terminates its extension. In this case, the viral DNA polymerase loses activity, binding to the triphosphate of acyclovir on the oligonucleotide.

The DNA polymerases of cytomegalovirus and Epstein-Barr virus are not as sensitized to the suppressive effect of acyclovir triphosphate as herpes viruses. Therefore, Valtrovir is used more for prophylactic than for therapeutic purposes against these viruses.

The selectivity of the action of acyclovir triphosphate on the biosynthesis of viral, rather than human, deoxyribonuclease is determined by the catalytic action of the enzyme thymidine kinase encoded by the virus and its greater “affinity” to the herpesvirus polymerase than to the human one.

Valtrovir, in addition to its antiviral activity, eliminates painful sensations, reducing their intensity and duration. It is also effective in postherpetic neuralgia.

Prevention of cytomegalovirus-associated infection with this drug reduces the likelihood of acute separation of the donor organ. Valtrovir prevents infection of people with reduced immunity and the development of diseases caused by the herpes virus.

[ 1 ], [ 2 ]

Pharmacokinetics

Oral Valtrovir has good absorption capacity and degradation rate. Almost the entire dose of the drug is hydrolyzed into acyclovir and L-valine. Following oral administration of 1 g of the drug, 54% of acyclovir is found in the systemic bloodstream. Its bioavailability is not affected by simultaneous food intake. The highest plasma density is detected less than two hours after a single dose of 0.25-1 g of the drug and is equal to 2.2-8.3 μg/ml. After three hours from the start of administration, the active ingredient is no longer detected in the serum. Cytochrome P450 enzymes are not involved in the metabolism of the drug.

The active ingredient binding to plasma albumin is low – 15%. The half-life of both single and multiple doses of Valtravir in individuals without renal impairment is approximately three hours. The active ingredient is eliminated by the urinary organs primarily (more than 4/5 of the dose) in the form of acyclovir and 9-carboxymethoxymethylguanine (a product of its metabolism). In severe renal pathologies, the half-life increases to 14 hours.

[ 3 ], [ 4 ], [ 5 ]

Dosing and administration

Herpesvirus type III infection (shingles) is treated by oral administration of two tablets of the drug three times a day (3 g per day). The duration of the therapeutic course is a week.

Therapy for lesions caused by herpes viruses HSV-1 and HSV-2 is more complex and varied.

Adults without immunodeficiency, according to the standard treatment regimen, should take one tablet (0.5 g) in the morning and evening at intervals of 12 hours.

The course of treatment for a newly diagnosed infection is from five to ten days; exacerbations are treated for three to five days.

Valtrovir is started when the first symptoms appear, especially with recurrent herpes. Exacerbation is preceded by prodromal phenomena, when there are no rashes yet, but it is already clear that they are about to appear. Their harbingers are tingling, slight pain, itching. This is the ideal time to start treatment. During this period, you can use both the standard scheme and the following: the first dose of Valcyte - two tablets (1 g) of the drug are taken at the first signs of exacerbation, the second (the same amount) - after 12 hours from taking the first. You can take the second dose a little earlier, but an interval of six hours must be maintained. The duration of treatment using this scheme is one day. Longer treatment in this way does not lead to high efficiency, but can cause overdose effects.

Prevention (suppression) of expected exacerbations of recurrent herpes simplex involves a single dose of one tablet (0.5 g) per day. Adult patients with immunodeficiencies are prescribed a two-time daily dose of one tablet (0.5 g).

To reduce the likelihood of a partner becoming infected with the herpes virus during sexual contact in immunocompetent adult heterosexual individuals with a number of relapses of no more than nine per year, it is recommended to dose the daily intake - one tablet (0.5 g) once. There is no information on reducing the likelihood of a sexual partner becoming infected in other groups of patients.

The preventive dosage for CMV infection in persons over 12 years of age is 2 g (four tablets of 0.5 g) four times a day at equal intervals. Preventive therapy should be started, if possible, immediately after organ transplantation. The standard course is three months; for patients at risk, it can be adjusted upwards.

If the patient has renal pathologies, it is necessary to monitor the level of hydration of the body. The dosage for this group of patients can be adjusted according to creatinine clearance indices (see the table below).

Indication for treatment	Creatinine clearance, ml/min	Valcyte Dosage
Herpes zoster (therapy) in adult immunocompetent patients, as well as in those with impaired immune system function	50 and above 30–49 10–29 less than 10	1g three times a day 1g twice a day 1g once a day 0.5g once a day
Herpes simplex (therapy)
In immunocompetent adult patients	30 and more less than 30	0.5g twice a day 0.5g once a day
Labile herpes (therapy) in adult immunocompetent patients	50 and above 30–49 10–29 less than 10	2g twice a day 1g once a day 0.5g twice a day 0.5g once a day
Preventive therapy
In immunocompetent adult patients	30 and more less than 30	0.5g once a day 0.25g once a day*
In adult patients with impaired immune system function	30 and more less than 30	0.5g twice a day 0.5g once a day
Prevention of CMV infection	75 and more 50–75 25–50 10–25 less than 10 or hemodialysis	2g four times a day 1.5g four times a day 1.5g three times a day 1.5g two times a day 1.5g once a day

_____________

* Use medications with the active ingredient valacyclovir hydrochloride, produced in the appropriate dosage.

For patients undergoing extrarenal blood purification procedures, Valtrovir is prescribed in dosages corresponding to a creatinine elimination rate slower than 15 ml/min. Postprocedural administration of the drug is prescribed.

Immediately after organ transplantation, there is a need for continuous monitoring of creatinine clearance and, accordingly, the dosage of Valtrovir.

In patients with mild or moderate cirrhotic changes in the liver with preserved synthesizing activity, the dosage regimen is not changed. There is no data on the need to adjust it in case of pronounced changes, however, it should be taken into account that the experience of Valtrovir therapy in such patients is very limited.

For elderly patients, in order to prevent the risk of kidney dysfunction, it is recommended to change the dosage of the drug in accordance with the table above. This age category of patients is recommended to maintain an optimal level of hydration of the body

[ 11 ]

Use Valtrovir during pregnancy

The active ingredient penetrates the placental barrier at any stage of pregnancy and is secreted into breast milk. Given this fact, it is not recommended to prescribe Valtrovir to women who are carrying a child and nursing mothers. Treatment with the drug during this period is possible only for vital indications.

Contraindications

Sensitization to the ingredients of the drug, children 0-12 years old.

[ 6 ], [ 7 ], [ 8 ], [ 9 ]

Side effects Valtrovir

The most frequently reported adverse effects of using this drug were headache and nausea.

The most dangerous side effects are: Moschkowitz disease, hemolytic uremic syndrome, acute renal dysfunction and neuropsychiatric disorders.

Possible adverse effects in the areas of:

• nerves and psycho-emotional state – headache, dizziness, disorientation, false perceptions of reality, decreased intelligence, overexcitement, generalized tremor, motor and/or speech disorders, psychotic symptoms, seizures, encephalopathy, coma;*
• hematopoiesis – decrease in the number of leukocytes** and platelets;
• immunity – anaphylaxis;
• respiratory system - shortness of breath;
• digestive organs – dyspeptic disorders;
• liver – liver function tests indices are above normal (reversible);
• dermis - itchy rashes, photosensitivity, angioedema;
• genitourinary system – renal dysfunction, acute renal failure, renal pain syndrome, presence of blood in the urine;***
• others - Moshkowitz disease and thrombocytopenia (rarely in combination) in people with late stages of AIDS who have been taking the drug for a long time in high doses - 8 g per day (the same is typical for patients with the same pathologies, but who have not taken the drug).

___________

* These effects are mostly reversible and are typical for individuals with renal dysfunction or other risk factors. In organ donor recipients taking the drug prophylactically in high doses (8 g daily), neuropsychiatric reactions are observed with a higher frequency than in patients receiving lower dose therapy.

** In individuals with immunodeficiency.

*** There are reports of formation of limited acyclovir accumulations in the renal tubules. Fluid intake should be monitored and optimized during treatment.

[ 10 ]

Overdose

Exceeding the standard dosage of Valtrovir may manifest itself in dyspepsia, development of acute renal dysfunction, neuropsychiatric disorders - disorientation, hallucinations, overexcitation, fainting, comatose state. In most cases, the symptoms of overdose occur in people with kidney diseases and the elderly, who have not been adequately adjusted in the dosage. It is necessary to carefully follow the dosage instructions of the drug.

Treatment is symptomatic. Purification of the blood from the active ingredient of the drug is effective with hemodialysis.

Interactions with other drugs

No significant interactions with other drugs have been identified.

Acyclovir is eliminated primarily by the urinary tract via the renal tubules. Any drugs that affect this excretion mechanism, taken in combination with Valtrovir, may increase the plasma levels of acyclovir. Coadministration of one gram of Valtrovir with Cimetidine and Probenecid (renal tubule blockers) increases the concentration and decreases the rate of clearance of acyclovir from the blood by the kidneys, but no dosage adjustment is required due to the large therapeutic index of acyclovir.

Patients treated with high doses of a drug (4g daily) require a more scrupulous approach to prescribing drugs that compete for excretion pathways. In this case, there is a risk of toxicity of one or both drugs and/or their metabolic products.

Combination with the immunosuppressant Mycophenolate Mofetil promotes an increase in the plasma concentration of acyclovir and the inactive metabolic product of the immunosuppressant.

It is necessary to regularly monitor kidney function when using high doses of Valtrovir (from 4 g daily) and other drugs that affect renal function (for example, Cyclosporine, Protoliq).

[ 12 ], [ 13 ]

Storage conditions

Store at temperatures below 25°C. Keep out of reach of children.

Shelf life

Shelf life is 2 years.