Valtrovir

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

Indications Valtrovir

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

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

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

Release form

It is produced in tablet form with film coating, unit of medicine contains 0.5 g valaciclovir hydrochloride.

Pharmacodynamics

The active substance of Valtrovir inhibits the enzymatic activity of the viral DNA polymerase, the inactivity of which interrupts the production of the nucleic acids of the virus and stops the multiplication and development of the microorganism. In the laboratory, alciclovir exhibits antiviral activity against HSV-1, HSV-2 (herpes simplex type I and type II), VZV (varicella), CMV (cytomegalovirus), Epstein-Barr, HHV-6 (human herpes VI type).

Entering the human body, valaciclovir hydrochloride hydrolyzes at a good speed and almost completely with the formation of acyclovir. The hydrolysis catalyst is the hepatic mitochondrial enzyme (valacyclovirhydrolase).

After that, acyclovir accumulates in the cells infected with herpesvirus. Viral thymidine kinase stimulates the onset of phosphorylation reactions to form acyclovir monophosphate, cell kinases catalyze the following reactions, resulting in the formation of active acyclovirtriphosphate, which suppresses the genomic replication of the deoxyribonuclease of herpevirus.

When cytomegalovirus is involved, conversion to acyclovirtriphosphate catalyzes UL 97 phosphotransferase. In both cases, the enzymes of viral cells complete the formation of acyclovirtriphosphate, which competes with the natural nucleoside, is included in the synthesized chain of viral DNA and terminates its prolongation. At the same time, the viral DNA polymerase loses its activity by binding to acyclovir triphosphate on the oligonucleotide.

DNA polymerase of cytomegalovirus and Epstein-Barr virus are not so sensitized to the overwhelming effect of acyclovir triphosphate as herpeviruses. Therefore, Valtrovir is used more for preventive, 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 thymidine kinase enzyme encoded by the virus and by a greater "affinity" for the herpevirus polymerase than for human.

In addition to antiviral activity, valtrovir eliminates painful sensations, reducing their intensity and duration. Effective also in postherpetic neuralgia.

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

[1], [2]

Pharmacokinetics

Oral Valtrovir has a good absorption capacity and a cleavage rate. Almost the entire dose of the drug is hydrolyzed to acyclovir and L-valine. As a result of oral administration of 1g of the drug, 54% of acyclovir is found in the systemic circulation. Its bioavailability is not affected by simultaneous intake of food. The greatest plasma density is detected less than two hours after a single dose of 0.25-1g of the drug and equals 2.2-8.3 μg / ml. At the end of three hours from the beginning of the intake, the active ingredient in the serum is no longer detected. Enzymes of cytochrome P450 do not participate in the process of drug metabolism.

Binding of the active ingredient of the drug with plasma albumins is low - 15%. The half-life period, due to both single-use and multiple-dose administration of Valtravir in persons without impaired renal activity, is approximately three hours. The active ingredient is eliminated mainly by the urinary organs (more than 4/5 of the dose) in the form of acyclovir and 9-carboxymethoxymethylguanine (the product of its metabolism). In severe renal pathologies, the elimination half-life increases to 14 hours. 

[3], [4], [5]

Dosing and administration

Infection with type III herpesvirus (shingles) is treated orally three times a day for two tablets of the drug (3g per day). The duration of the therapeutic course is a week.

Therapy of lesions caused by HSV-1 and HSV-2 herpesviruses is more complex and diverse.

Adults without immunodeficiency under the standard treatment regimen should take one tablet (0.5g) in the morning and in the evening with an interval of 12 hours.

The course of treatment of the primary infection is from five to ten days, the exacerbations are treated for three to five days.

Valtrovir begins to take onset of the first symptoms, especially with relapsing 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, minor soreness, itching. This is the ideal time to start treatment. During this period, you can apply both the standard scheme and the following: the first dose of Valtsita - two tablets (1g) of the drug is taken at the first signs of exacerbation, the second (the same amount) - after 12 hours from the first. You can take the second portion a little earlier, but the interval at six o'clock must necessarily be sustained. The duration of treatment with this scheme is one day. Longer treatment in this way does not lead to high performance, but can cause overdose effects.

Prevention (suppression) of the expected exacerbations of recurrent herpes simplex involves a single dose of one tablet (0.5 g) per day. Adult patients with immunodeficiency are given twice daily intake of one tablet (0.5 g).

To reduce the likelihood of partner infection with herpesvirus during sexual contact with immunocompetent adults, heterosexual individuals with a relapse rate of no more than nine per year, it is recommended to dose daily intake - one tablet (0.5 g) once. Information about reducing the likelihood of infection of the sexual partner in other groups of patients is not available.

The prophylactic dosage of infection with CMV virus to people over 12 years old is 2g (four tablets of 0.5g) four times a day at regular intervals. It is necessary to start preventive therapy as soon as possible after organ transplantation. Standard course - three months, patients from the risk group can be adjusted upwards.

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

Indication for treatment	Creatinine clearance, ml / min	Dosage of Valcite
Shingles (therapy) in adults with immunocompetent patients, as well as with impaired functions of the immune system	50 and more 30-49 10-29 less than 10	1g three times / day 1g twice / day 1g once / day 0.5g once / day
Herpes simplex (therapy)
In adult immunocompetent patients	30 and more is less than 30	0.5 g twice / day 0.5 g once / day
Labile form of herpes (therapy) in adult immunocompetent patients	50 and more 30-49 10-29 less than 10	2d twice / day 1g once / day 0.5g twice / day 0.5g once / day
Preventive therapy
In adult immunocompetent patients	30 and more is less than 30	0.5g once / day 0,25 g once / day *
In adults with impaired immune function	30 and more is less than 30	0.5 g twice / day  0.5 g once / day
Prevention of CMV infection	75 and more 50-75 25-50 10-25 less than 10 or hemodialysis	2d four times a day 1.5g four times / day  1.5g three times / day  1.5g twice / day 1.5g once / day

 

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* Use medicines with active substance valacyclovir hydrochloride, available with appropriate dosage.

Patients undergoing non-renal blood purification procedures are prescribed valtivir in dosages corresponding to the rate of creatinine clearance slower than 15ml / min. Postprocedural drug administration is prescribed.

Immediately after the organ transplant surgery, there is a need to constantly monitor the clearance of creatinine and, accordingly, the dosage of Valtrovir.

Patients with cirrhotic changes in the liver of mild or moderate severity with preserved synthesizing activity do not undergo a change in the dosing regimen. Data on the need to correct it and with pronounced changes are absent, yet, it should be noted that the experience of therapy with Valtrovir of such patients is very limited.

Patients of advanced age, in order to prevent the risk of disrupting the kidneys, it is recommended to change the dosage of the drug in accordance with the table above. This age group of patients is recommended to maintain the optimal level of hydration of the body

[11]

Use Valtrovir during pregnancy

The active ingredient penetrates the placental barrier at any time of pregnancy and is secreted into breast milk. Considering this fact, it is not recommended to appoint Valtrovir to women who are nursing 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.

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

Side effects Valtrovir

The undesirable consequences of using this drug in the form of headache and nausea were most often recorded.

The most dangerous side effects are: Moshkowitz disease, hemolytic-uremic syndrome, acute renal dysfunction and neuropsychic disorders.

Possible undesirable effects in the areas:

• nerves and psycho-emotional state - headache, dizziness, disorientation, imaginary perception of reality, decreased intelligence, overexcitation, generalized tremor, motor and / or speech disorders, psychotic symptoms, convulsive seizures, encephalopathy, coma; *
• hematopoiesis - a decrease in the number of leukocytes ** and platelets;
• immunity - anaphylaxis;
• respiratory system - shortness of breath;
• digestive organs - dyspeptic disorders;
• liver - indices of liver tests above the norm (reversible);
• dermis - itchy rashes, photosensitivity, angioedema;
• genitourinary system - renal dysfunction, acute renal failure, renal pain syndrome, presence of blood in the urine; ***
• others - Moszkowitz disease and thrombocytopenia (occasionally in combination) in people with late stages of AIDS who took a long time medication at high dosages - 8g per day (the same is true for patients with the same pathologies but not taking the drug).

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* These effects are predominantly reversible and are characteristic of individuals with kidney dysfunction or other risk factors. The recipients of the donor organs taking the medicine for prophylactic purposes at high dosages (8g daily), neuropsychic reactions are observed with a greater frequency than in patients with lower dosage therapy.

** In persons with immunodeficiency.

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

[10]

Overdose

Exceeding the standard dosage of Valtrovir may be manifested by dyspepsia, the development of acute renal dysfunction, neuropsychiatric disorders - disorientation, hallucinations, overexcitation, fainting, coma. In most cases, the symptomatology of excess dosage occurs in individuals with kidney and elderly disease who have not been adequately adjusted for the dose. It is necessary to follow the dosage instructions carefully.

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

Interactions with other drugs

Significant mutual actions with other drugs have not been identified.

Acyclovir is eliminated mainly by the urinary organs through the renal tubules. Any drugs that affect this excretion mechanism, taken in conjunction with Valtrovir, can increase the plasma content of acyclovir. The joint administration of one gram of Valtrovir with cimetidine and Probenecid (renal tubular blockers) increases the concentration and reduces the rate of purification in the kidneys from acyclovir, but dosage adjustment is not required due to the extensive therapeutic index of acyclovir.

Patients who are treated with high doses of the drug (from 4 g daily) require a more scrupulous approach to prescribing medications for them - competitors for excretion routes. In this case, there is a risk of toxicity of one or both of the drugs and / or products of their metabolism.

Combination with the immunosuppressor Mycophenolate Mofetil helps increase the plasma concentration of acyclovir and the inactive product of the immunosuppressant metabolism.  

It is necessary to regularly monitor the kidneys when combined use of high doses of Valtrovir (from 4 g daily) and other drugs affecting the kidney function (for example - Cyclosporine, Protolyca).

[12], [13]

Storage conditions

Store in accordance with the temperature regime up to 25 ° C. Keep away from children.

Shelf life

Shelf life 2 years.