Valacyclovir film-coated tablets 500 mg 10 pcs (Ozone-Atoll)

Valacyclovir

Inside. The drug Valacyclovir is taken regardless of food intake, the tablets should be washed down with water.

Treatment of herpes zoster

Adults

The recommended dose is 1000 mg 3 times a day for 7 days.

Treatment of infections caused by HIV

Adults

The recommended dose for treatment of an episode is 500 mg 2 times a day.

In the case of primary herpes, which can occur in a more severe form, treatment should begin as early as possible, and its duration can be increased from 5 to 10 days. In case of relapse, treatment should continue for 3 or 5 days. For recurrent HSV, it is ideal to prescribe valacyclovir in the prodromal period or immediately after the first symptoms of the disease appear.

As an alternative, valacyclovir 2 g twice daily is effective for the treatment of herpes labialis. 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 exceeding the duration of treatment does not lead to an additional clinical effect. Therapy should be started when the earliest symptoms of herpes labialis (ie, tingling, itching, burning) appear.

Prevention (suppression) of recurrent infections caused by HSV

Adults

In patients with preserved immunity, the recommended dose is 500 mg once daily.

In patients with immunodeficiency, the recommended dose is 500 mg 2 times a day.

Prevention of transmission of genital herpes to a healthy partner when taken as suppressive therapy in combination with safe sex

For infected immunocompetent individuals with relapses no more than 9 times a year, the recommended dose of valacyclovir is 500 mg once a day for a year or more every day.

There are no data on infection prevention in other patient populations.

Prevention of infections caused by cytomegalovirus (CMV) and diseases after solid organ transplantation

Adults and teenagers aged 12 years and older

The recommended dose is 2 g 4 times a day, prescribed 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 the course of treatment can be extended.

Special patient groups

Patients with impaired renal function

Treatment of herpes zoster and infections caused by HSV, prevention (suppression) of relapses of infection caused by HSV, prevention of transmission of genital herpes to a healthy partner.

It is recommended to reduce the dose of valacyclovir in patients with a significant decrease in renal function (see dosage for renal failure in the table). In such patients, it is necessary to maintain adequate water and electrolyte balance.

There is no experience with the use of valacyclovir in children with creatinine clearance values ​​less than 50 ml/min/1.73 m2.

For patients on hemodialysis, it is recommended to use valacyclovir immediately after the end of the hemodialysis session at the same dose as in patients with creatinine clearance less than 15 ml/min.

Prevention of cytomegalovirus (CMV) infection after transplantation

The prescribing regimen for valacyclovir in patients with impaired renal function should be established in accordance with the table below.

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

Creatinine clearance should be determined frequently, especially during periods when renal function changes rapidly, such as immediately after transplantation or engraftment, and the dose of valacyclovir is adjusted according to creatinine clearance.

Patients with liver dysfunction

In adult patients with mild or moderate hepatic impairment with preserved synthetic function, no dose adjustment of Valacyclovir is required.

Pharmacokinetic data in adult patients with severely impaired liver function (decompensated cirrhosis), with impaired synthetic liver function and the presence of portacaval anastomoses also do not indicate the need to adjust the dose of Valacyclovir, however, clinical experience with this pathology is limited.

Children under 12 years of age

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

Elderly patients
No dosage adjustment is required unless there is significant impairment of renal function. It is necessary to maintain adequate water and electrolyte balance.

Valacyclovir tablet p/pl/o 500 mg N40 (Synthesis)

The drug Valacyclovir is taken regardless of food intake, the tablets should be washed down with water. Treatment of skin and mucous membrane infections caused by HSV, including newly diagnosed and recurrent genital herpes (Herpes genitalis), as well as labial herpes (Herpes labialis) Immunocompetent adults and adolescents aged 12 to 18 years. The recommended dose is 500 mg 2 times a day. In case of relapse, treatment should continue for 3 or 5 days. In the case of primary herpes, which can occur in a more severe form, treatment should begin as early as possible, and its duration should be increased from 5 to 10 days. In case of relapses of HSV, the most correct prescription of the drug Valaciclovir is considered to be in the prodromal period or immediately after the appearance of the first symptoms of the disease. The use of valacyclovir may prevent the development of lesions if it is given at the first signs and symptoms of relapse due to HSV. As an alternative treatment for labial herpes, the use of the drug Valacyclovir at a dose of 2000 mg 2 times a day for 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 exceeding the duration of this course of treatment does not lead to additional clinical benefit. Therapy should be started when the earliest symptoms of herpes labialis (ie, tingling, itching, burning) appear. Prevention (suppression) of recurrent infections of the skin and mucous membranes caused by HSV, including genital herpes, including in adults with immunodeficiency. Immunocompetent adults and adolescents aged 12 to 18 years. In immunocompetent patients, the recommended dose is 500 mg once daily. After 6-12 months of treatment, it is necessary to evaluate the effectiveness of therapy. Adults with immunodeficiency. In adult patients with immunodeficiency, the recommended dose is 500 mg 2 times a day. After 6-12 months of treatment, it is necessary to evaluate the effectiveness of therapy. Prevention of infections caused by HSV and diseases after solid organ transplantation. Adults and teenagers aged 12 to 18 years. The recommended dose is 2000 mg 4 times a day, prescribed as early as possible after transplantation. The dose should be reduced depending on creatinine clearance. The duration of treatment is usually 90 days, but in high-risk patients the course of treatment may be extended. Treatment of herpes zoster (Herpes zoster) and ophthalmic herpes zoster. Adults. The recommended dose is 1000 mg 3 times a day for 7 days. Special groups of patients. Children. The effectiveness of treatment with Valacyclovir in children has not been studied. Elderly patients. It is necessary to take into account the possible impairment of renal function in elderly patients, and the dose of Valaciclovir should be adjusted accordingly. It is necessary to maintain adequate water and electrolyte balance. Patients with impaired renal function. It is recommended to reduce the dose of Valaciclovir in patients with severe renal impairment (see dosage regimen in Table 2). In such patients, it is necessary to maintain adequate water and electrolyte balance. Dose adjustment of Valacyclovir for use in adults and adolescents aged 12 to 18 years with impaired renal function. Herpes zoster and ophthalmic herpes zoster in immunocompetent adults (treatment): at least 50 - 1000 mg 3 times a day, from 30 to 49 - 1000 mg 2 times a day, from 10 to 29 - 1000 mg 1 time a day, less than 10 - 500 mg 1 time per day. HSV (treatment). Immunocompetent adults and adolescents aged 12 to 18 years: at least 30-500 mg 2 times a day, less than 30-500 mg 1 time a day. Labial herpes in immunocompetent adults and adolescents aged 12 to 18 years (treatment): at least 50 - 2000 mg 2 times a day, from 30 to 49 - 1000 mg 2 times a day, from 10 to 29 - 500 mg 2 times per day, less than 10 - 500 mg 1 time per day. HSV (prevention (suppression)). Immunocompetent adults and adolescents aged 12 to 18 years: at least 30-500 mg once a day, less than 30-500 mg once every two days. Adults with immunodeficiency: at least 30-500 mg 2 times a day, less than 30-500 mg 1 time a day. Prevention of infections caused by CMV in adults and adolescents aged 12 to 18 years: at least 75 - 2000 mg 4 times a day, from 50 to 75 - 1500 mg 4 times a day, from 25 to 50 - 1500 mg 3 times per day, from 10 to 25 - 1500 mg 2 times a day, less than 10 or in patients on hemodialysis - 1500 mg 1 time per day. Additional information for indication: treatment of skin and mucous membrane infections caused by HSV, including newly diagnosed and recurrent genital herpes (Herpes genitalis), as well as labial herpes (Herpes labialis). There is no experience with the use of Valacyclovir in children with creatinine clearance values ​​less than 50 ml/min/1.73 m2. Additional information for the indication: Prevention of CMV infections and morbidity after solid organ transplantation. Creatinine clearance should be determined frequently, especially during periods when renal function changes rapidly, such as immediately after transplantation or engraftment, and the dose of Valacyclovir is adjusted accordingly. with creatinine clearance indicators. Additional information for the indication: Treatment of herpes zoster and herpes zoster ophthalmicus Valacyclovir should be used after hemodialysis in patients undergoing intermittent hemodialysis. Patients with impaired liver function. Based on a study using a single dose of valaciclovir 1000 mg in adult patients with mild to moderate liver cirrhosis (with preserved synthetic liver function), no dose adjustment of valaciclovir is required. Pharmacokinetic data in adult patients with severe liver dysfunction (decompensated cirrhosis), impaired synthetic liver function and the presence of portacaval anastomoses also do not indicate the need for dose adjustment of Valacyclovir, however, clinical experience with these pathologies is limited. Information about doses greater than 4000 mg per day for patients with infections caused by HSV and CMV is listed in the section "Special Instructions."

Etiotropic therapy of herpes simplex: focus on valacyclovir

The first description of the symptoms of a “cold on the lips” was made by the famous Roman physician Herodotus. The first attempts at organized prevention of transmission of the “creeping” disease also date back to ancient times. The Roman Emperor Tiberius issued a decree banning public kissing in the Senate to stop the spread of infection. The disease was also known to the doctors of Ancient Greece. The writings of Hippocrates mention a skin disease that can quickly spread, “spread” among people, called “herpain”, which means “creeping”; this word was subsequently transformed into “herpes” [1].

Currently, according to WHO, the infection rate of the population with the herpes simplex virus (HSV) is extremely high and is actually approaching 100%. Recurrent forms of HSV affect about 20% of the population, and the number of cases increases every year by an average of 15–17%. The incidence of herpes viral infection ranks second among infectious pathologies, second only to influenza. In the structure of the incidence of sexually transmitted infections (STIs), genital herpes (GG) is in third place after gonorrhea and non-gonococcal urethritis, and, according to foreign studies, GG is the most common STI in the world, the most common cause of genital ulcers, and also an important risk factor for HIV acquisition and transmission [2–6].

HSV enters the human body through mucous membranes and skin. The main routes of infection are airborne and sexual. Primary infection is accompanied by viral replication only at the site of invasion. Next, the virus enters the sensory paravertebral ganglia by hematogenous or axonoplasmic route, where it persists for life, often leading to the latent phase of infection [3, 7].

Virus carriage in most cases is not accompanied by clinical manifestations of the disease. As is known, a child receives antibodies to HSV transplacentally from the mother, but their titer decreases significantly by the end of the first year of life, and by the third year they are completely eliminated from the body. In 80–90% of people aged 2 to 5 years, against the background of a decrease or absence of specific antibodies, upon the first contact of the body with HSV, infection with primary herpes occurs. Infection in most cases is not accompanied by clinical manifestations, but in a number of cases primary herpes develops - an acute disease.

Most often, primary herpes manifests itself in the form of herpetic gingivostomatitis. Single or multiple vesicles appear on the mucous membrane of the oropharynx, which quickly open to form painful erosions, which are then covered with a whitish coating. The oral mucosa and gums become swollen, hyperemic, cyanotic and sharply painful. The pain syndrome can be so severe that it makes it difficult to eat and drink. Gradually, acute inflammatory phenomena subside and erosions begin to epithelialize from the periphery to the center. Complete regression of the rash occurs after 2–3 weeks. After the disappearance of clinical manifestations of primary herpes or asymptomatic infection, the herpes viral infection becomes latent. During this period, HSV remains in an inactive state in the nerve ganglia, with HSV-1 most often infecting the trigeminal ganglia, and HSV-2 reactivated primarily from the sacral ganglia. At the same time, the production of antibodies to HSV begins. However, when immunity decreases under the influence of a number of unfavorable factors, relapses of the disease can occur with varying frequency - from several days to several months or even years [2, 5, 7].

Reactivation of herpes infection depends on a number of endogenous and exogenous factors [2, 7–10]:

• the amount of latent viral DNA located in the ganglia;
• type-specific sequences in the virus genome that determine the frequency of reactivation and relapse in a specific anatomical region;
• the patient’s immune status (decrease in the levels of alpha and gamma interferons, as well as CD4+ CD8± subpopulation of T-lymphocytes);
• exposure to UV radiation and hypothermia;
• psycho-emotional stress;
• increased level of physical activity;
• changes in hormonal rhythms (for example, menstruation);
• mechanical trauma, including after invasive cosmetic procedures;
• drinking alcohol.

Despite obvious clinical symptoms, sometimes doctors have difficulty diagnosing herpes infection. Thus, according to foreign studies, only 20% of those infected with the herpes virus are diagnosed with this disease; in 60%, the herpes infection, despite obvious symptoms, remains unrecognized. And in approximately 20% of the population, the disease occurs in a latent form, and this further complicates timely diagnosis and adequate treatment of the disease [4, 8, 10].

In the past, there was an opinion that HSV-1 selectively affected the orofacial area, and HSV-2 - the external genitalia. In recent decades, data have been obtained on their general tropism: both viruses can infect both the oral and genital areas, causing acute and recurrent forms of the disease. However, the incidence of HSV-2 does correlate with sexual activity and the prevalence of the virus among potential sexual partners; Antibodies to HSV-2 are rarely detected before sexual activity begins. HSV-2 causes orafascial herpes only in 10–20% (HSV-1 - 80–90%) of cases. The role of HSV-1 in the development of HH throughout the world is constantly growing. In the UK, for example, it was found that in 50% of cases of manifestations of primary HH were caused by HSV-1, mainly in sexually active women aged 16–20 years [2, 4, 8, 11–13].

There are two alternative hypotheses that explain the mechanisms of HSV persistence in the body - statistical and dynamic. According to the statistical hypothesis, HSV is found in the cells of the paravertebral sensory ganglion in an integrated (non-reproductive) state. Under the influence of a “trigger factor,” the virus moves from the ganglion along the axon of the peripheral nerve to epithelial cells, where it replicates. It is believed that this is largely due to cellular susceptibility and weakening of the patient's immunological control. The dynamic hypothesis assumes constant replication of the virus and its release from the ganglion. Reaching along the skin nerve, HSV causes microfoci of infection, restrained by defense mechanisms, which prevents relapses or weakens the manifestations of the disease. The development of relapses is influenced by the state of local immunity, the suppression of which contributes to the replication of the virus that has reached the skin [3].

The facial area is one of the most favorite localizations for HSV manifestations. Most often, the rashes are located in the area of ​​the red border of the lips (Fig. 1), in the vestibule and on the wings of the nose, in the perioral area, on the chin, and much less often in the area of ​​the cheeks and forehead. With the development of a viral infection in the genital area, the rashes are often located in the pubic area, shaft of the penis, glans, on the inner layer of the foreskin, head groove - in men (Fig. 2) and in the vulva and perineum - in women. The blisters here usually exist for an extremely short time, quickly opening with the formation of painful erosions that do not heal for a long time due to constant maceration. Women may experience swelling, as well as the spread of rashes from the vulva to the mucous membrane of the vagina and cervix, which is accompanied by increased subjective sensations and the appearance of discharge. In some women, relapses of the disease coincide in time with the menstrual cycle (menstrual herpes). Herpetic rashes in this form usually appear on the skin of the buttocks and extend to the thighs. One unusual location for HSV rashes to be aware of is the fingers and palms. This localization of rashes is typical for medical workers who come into contact with the skin and mucous membranes of infected patients (for example, dentists), dressmakers due to the possibility of frequent injury, and hairdressers [4, 7, 8, 11].

In clinical practice, the most common form of recurrent herpes simplex is found. Regardless of the location of the pathological process, the disease in most cases (45–60%) begins with subjective sensations - “harbingers of relapse.” On average, a day before the appearance of the rash, mild sensations arise in the form of tingling, itching, burning, and, less often, pain. There may also be a disturbance in the general condition: a feeling of fatigue, weakness, headache, chills, a slight increase in temperature. These symptoms are usually mild, but most patients, especially with frequent recurrences of herpes simplex, immediately pay attention to them. After 1–2 days, erythema appears in the area of ​​projection of subjective symptoms, accompanied by moderate swelling, against the background of which small grouped hemispherical bubbles begin to form. The contents of the bubbles are initially transparent, then become cloudy. Having existed from several hours to several days, they turn into erosions covered with thin serous crusts. After 7–9 days, the crusts are rejected, leaving behind a pinkish or brownish-brown secondary spot, which usually regresses after 7–14 days [7].

Thus, in the classical version, 4 successive stages of the disease can be distinguished: erythematous, vesicular, crustose, and the stage of clinical recovery. In some patients with frequent relapses of herpes in the same place or with the addition of a secondary infection, shallow small scars may remain at the site of resolved herpetic rashes. A relapse of herpes simplex may be accompanied by a reaction from the lymphatic system in the form of regional lymphadenitis and lymphangitis, the addition of a secondary infection, and symptoms of damage to the peripheral nervous system. In severe cases, skin manifestations of herpetic infection are aggravated by symptoms of general intoxication: low-grade fever, sweating, headache, malaise, joint pain, gastrointestinal disorders [2, 4, 7, 9].

The greatest difficulty in recognizing herpes viral infection occurs with abortive forms of HSV. H. Gouqerot was the first to draw attention to the existence of abortive forms of herpes simplex in 1921. A feature of these forms is the absence of the most characteristic stage of development of the pathological process - the stage of vesicle development. The occurrence of these forms of HSV infection is apparently associated with an increase in the body’s immune forces, when the pathological process does not develop beyond the initial stage of the disease. Abortive forms include erythematous, papular and pruritic. The duration of the disease in this case ranges from several days to a week [7, 8].

In rare cases, there are atypical manifestations of herpes simplex, the diagnosis of which causes great difficulties for doctors. These forms include rupioid, edematous, hemorrhagic, elephantiasis-like and impetigo-like. In immunocompromised patients, herpes infection can be severe. Severe forms include Kaposi's herpetic eczema, which occurs in children and adolescents against the background of severe atopic dermatitis, as well as ulcerative and generalized forms of HSV, often detected in patients with malignant tumors and leukemia [7].

Therapeutic tactics for managing patients with herpes viral infection are primarily aimed at effectively stopping relapses of the disease, reducing the risk of transmitting herpes to a healthy sexual partner or newborn (in the case of genital herpes), as well as preventing the development of clinical complications. The treatment strategy is determined by a number of factors: the severity of the clinical symptoms of the disease, the frequency of relapses, the state of the immune system, the presence or absence of concomitant pathology, psychosocial status, as well as the economic aspects of therapy. The main drugs used in the treatment of HSV are acyclic nucleosides: acyclovir, valacyclovir, famciclovir. They have a highly specific etiotropic antiviral effect that blocks HSV replication. Prescription of etiotropic therapy is the world standard for effective treatment of herpes infection.

Therapeutic approaches to the treatment of HSV with acyclic nucleosides include 2 regimens [2, 14–18]:

• episodic systemic antiviral therapy (done during relapse). It is most effective when initiated by the patient himself in the early stages of the disease (during the manifestation of precursors or on the 1st day of relapse). Prescribing antiherpetic treatment at a later date does not always lead to rapid relief of relapse.
• suppressive or preventive antiviral therapy, which is prescribed for a period of 6–12 months. patients: with frequent relapses of HSV (more than 6 episodes per year);
• with severe and prolonged episodes of the disease (impairing the quality of life in both HS and orofacial herpes);
• young women and girls immediately after the first episode of HS;
• with herpes simplex in association with recurrent erythema multiforme;
• with pronounced psycho-emotional reactions to the disease;
• undergoing chemical or abrasive procedures in the facial area and surgical procedures in the trigeminal nerve area;
• certain categories of medical workers in order to reduce the possibility of transmission of the virus.

According to studies, suppressive therapy prevents relapses of herpes simplex in 80% of cases and reduces the risk of transmitting the infection to a sexual partner during HH by 48% [14, 17, 19].

Systemic acyclic nucleosides presented on our pharmaceutical market have the same mechanism of antiviral action - selective phosphorylation in HSV-infected cells and competitive substrate inhibition of DNA polymerase, leading to the end of the reading of the viral DNA strand. The drugs differ in their bioavailability, solubility and concentration in the blood plasma [6, 15, 20].

The first acyclic nucleoside - acyclovir - has rightfully earned a reputation as an effective and safe drug, however, its low bioavailability (20%) and inconvenient dosage regimen (3-5 times / day), and therefore low compliance, led to the creation of drugs with higher bioavailability and compliance - valacyclovir and famciclovir [6, 15].

Valaciclovir is the hydrochloride salt of acyclovir L-valyl ester. This is a prodrug that in the body, under the influence of valacyclovir hydrolase, is quickly and almost completely converted into L-valine and acyclovir, which, after phosphorylation, acquires specific activity. Acyclovir is a structural analogue of purine nucleosides (normal components of DNA), interacts with viral DNA polymerase and blocks viral replication. Selective antiherpetic activity is due to affinity for thymidine kinase Herpes simplex types 1 and 2, Varicella zoster and Epstein-Barr virus. Under the influence of viral thymidine kinase, it is transformed into acyclovir monophosphate, with the participation of human cell guanylate kinase - into acyclovir diphosphate and then into the active form of acyclovir triphosphate. Triphosphate blocks viral DNA replication by competitively inhibiting viral DNA polymerase and inhibiting chain elongation.

The clinical efficacy and high systemic safety of valacyclovir have been proven in numerous domestic and foreign studies [21].

It was found that when taken orally, 54% of valacyclovir is absorbed from the intestine, compared to 20% when taking acyclovir. After taking valacyclovir, the same concentration of the drug substance is created in the blood that could be created only with intravenous administration of acyclovir. This feature provides the drug with a longer and more pronounced effect. When administered orally, its bioavailability is 3–4 times higher than that of acyclovir, while the safety profile is similar to acyclovir [6, 15, 16].

Two randomized, placebo-controlled, multicenter studies were conducted abroad on the treatment of exacerbations of orofacial herpes using short courses of valacyclovir. Both studies included 1,856 men and women. All patients were randomly divided into three equal groups: group 1 received valacyclovir 2 g 2 times a day for one day (one-day treatment); second - 2 g 2 times a day for the 1st day, then 1 g 2 times a day for the 2nd day (two-day treatment); the third group received a placebo. Therapy began when the first signs of exacerbation of herpes simplex appeared. As a result of the studies, similar results were revealed: the average duration of the disease statistically significantly decreased by 1.1 days with one-day treatment and by 0.7 days with two-day treatment. The number of patients in whom the progression of an exacerbation of herpetic infection was stopped or prevented increased by 6.4% with a one-day and by 8.5% with a two-day dosage regimen. The duration of existence of herpetic eruptions and subjective symptoms (pain, itching, discomfort) also significantly decreased in the groups of patients taking valacyclovir compared with the group of patients receiving placebo [22].

Valaciclovir has been proven to be highly effective as a suppressive therapy for HH. O. I. Letyaeva, O. A. Gisinger, O. R. Ziganshin, at the Ural State Medical University (Ekaterinburg), conducted a comparative study of the antiherpetic activity of acyclic nucleosides prescribed as suppressive therapy. The study involved 48 women with recurrent HH, who were divided into 2 groups. Group 1 (22 women) received acyclovir at a dosage of 400 mg 2 times/day, group 2 (26 women) received valacyclovir at a dose of 500 mg 1 time/day. Therapy was carried out for 6 months. When comparing the clinical effectiveness of the drugs, it was revealed that relapses after treatment in patients from the first group were observed 2.5 times more often than in women from the second group. Seven women receiving acyclovir for various reasons violated the prescribed regimen of taking the drug; there were only two such patients in the valacyclovir group. They noted that valacyclovir was well tolerated and had no side effects with long-term use. The frequency of detection of HSV after a year in the first group was almost 2 times higher and amounted to 13.6% - versus 7.59% in the second group of women [6].

A number of foreign studies have found that suppressive antiherpetic therapy with valacyclovir for HSV-2 reduces HIV replication, and therefore the viral load, and the effectiveness of valacyclovir in HIV-positive patients with HH was higher than when taking acyclovir. Thus, the level of HIV RNA in the blood plasma when taking valacyclovir is 2.94 copies/ml, and when taking acyclovir it is already 3.56 copies/ml [23, 24].

At the State Research Center of the Institute of Immunology of the FMBA, the effectiveness of systemic acyclic nucleosides: acyclovir, valacyclovir, famciclovir was studied in patients with recurrent HH, who had an average of about 6 relapses of the disease per year. The rashes were localized in the genital area, perineum, sacrum, and thighs. Therapy was prescribed according to two regimens: episodic (10 days) and suppressive (6 months). A total of 265 patients (96 men and 169 women) were examined and treated. A greater effectiveness of suppressive therapy was noted compared to episodic therapy: in 30% of patients with HH (regardless of the prescribed drug), the virus was again detected on the mucous membrane on the 28th day after the end of episodic therapy. Against the background of suppressive therapy after 1 month. the virus was not detected in any patient. The remission period after treatment with acyclovir was 4.1 months, with famciclovir - 9.2 months, and with valacyclovir - 10.5 months. [25].

The high effectiveness of suppressive therapy compared to episodic therapy has been proven in patients with labial herpes. The study included patients of both sexes who had 3 episodes of herpetic infection during the last year, who were divided into 2 groups: 1. those who took episodic antiherpetic therapy when the first signs of HSV appeared (in the prodrome) according to the regimen of 2 g / 2 times / day; 2. received preventive antiviral therapy according to the regimen of 1 g/day for six months. It was noted that the relapse rate within 3 months. after treatment is much higher in patients receiving episodic therapy. On average, when receiving episodic therapy, relapse occurred on the 81st day. No relapses were detected in the observed period (120 days) in patients receiving suppressive therapy. There were no statistically significant differences in the effect of the main clinical symptoms (lesion area, itching, etc.) on regression, with the exception of pain, which was significantly better reduced in the second group. The frequency of side effects in patients from the first group was higher and amounted to 6%, while in patients from the second group it did not exceed 3% [26].

At the Department of Skin and Venereal Diseases of the Moscow State Medical University, a comparative study of various forms of valacyclovir in the treatment of orofacial herpes was conducted. 40 (28 women and 12 men) patients aged 23 to 34 years were observed. The duration of the disease varied from 3 to 5 years, the frequency of relapses was 4–6 times a year. Verification of the diagnosis was carried out on the basis of a PCRrealtime molecular genetic study with determination of the viral load and HSV DNA typing. Using a random sampling method, patients were divided into two groups comparable in number, age composition, and severity of the disease. The 1st group (20 patients) was prescribed episodic therapy - the original valacyclovir 500 mg 2 times a day, the 2nd group (20 patients) received its generic according to the same regimen. The duration of treatment in both groups was 5 days. The duration of the relapse did not exceed 3–5 days. It was found that relief of itching and new rashes was comparable in both groups and took an average of 1–2 days. In 40% of patients in both groups, relapse was relieved on the 3rd day of drug use. In 55% of patients in both groups, epithelization of erosions was observed on the 4-5th day of treatment. In only 5% of patients, the use of drugs did not affect the duration of relapse. During control studies 30 days after the end of therapy, HSV DNA of types 1 and 2 was not detected in scrapings from the skin and mucous membranes in any patient. No adverse reactions were noted during or after use of both drugs. The authors conclude that both the original valacyclovir and the generic are comparable in effectiveness and safety [27].

Thus, we can conclude that long-term experience of use in domestic and foreign clinical practice and evidence-based studies on the effectiveness and safety of valacyclovir allow us to consider it the undoubted leader among systemic antiviral drugs. The drug has high antiviral activity against HSV-1 and HSV-2 and can be used both to treat relapses of herpes (episodic therapy) and to prevent relapses of infection (suppressive therapy). Prolonged therapy is of paramount importance both for adequate control of recurrent infections and for the prevention of transmission of HH to sexual partners. The absence of relapses of infection while taking the drug contributes to a significant reduction in psycho-emotional experiences about the disease, psychological rehabilitation of patients and a significant increase in quality of life. However, long-term antiviral therapy with the original valacyclovir is highly costly, and patients often cannot use it for economic reasons. In this regard, the line of generics of the original drug is constantly updated with new generic drugs. Reducing the cost of therapy increases its availability, and consequently, patient adherence to treatment. From this point of view, the use of a reproduced acyclic nucleoside, the drug Valogard (Farmak), seems promising.

Valogard is available as tablets containing 556 mg of valacyclovir hydrochloride, which is equivalent to 500 mg of valacyclovir. In the treatment of herpes zoster, Valogard helps relieve pain, reduces its duration and the percentage of patients with pain caused by herpes zoster, including acute and postherpetic neuralgia. The use of Valogard is effective in the treatment of infections of the skin and mucous membranes caused by HSV, including newly diagnosed and recurrent HH (Herpes genitalis), as well as labial herpes (Herpes labialis); prevention of recurrence of infections of the skin and mucous membranes caused by HSV, including HH; prevention of transmission of HH to a healthy partner when taken as suppressive therapy in combination with safe sex. In addition, in adults and adolescents from 12 years of age, Valogard is used to prevent cytomegalovirus infection, as well as acute transplant rejection (in patients with kidney transplants), opportunistic infections and other herpes viral infections after organ transplantation.

When treating herpes zoster in adults, the recommended dose of Valogard is 1000 mg 3 times a day for 7 days. Treatment of infections caused by HSV: adults - the recommended dose for treatment of an episode is 500 mg 2 times / day for 5 days. In more severe cases of disease onset, the duration of treatment should be increased from 5 to 10 days.

For recurrent HSV, it is ideal to prescribe Valogard in the prodromal period or immediately after the first symptoms of the disease appear. As an alternative for the treatment of labial herpes, the administration of the drug Valogard at a dose of 2 g 2 times / day is effective. The second dose should be taken approximately 12 hours (but not earlier than 6 hours) after taking the first dose. When using this dosage regimen, the duration of treatment is 1 day. Prevention of relapses of infections caused by HSV: adults - in patients with preserved immunity, the recommended dose is 500 mg 1 time / day, in patients with immunodeficiency - 500 mg 2 times / day.

To prevent infection of a healthy partner with HH, the recommended dose of Valogard for use by infected immunocompetent persons with relapses no more than 9 times a year is 500 mg 1 time per day daily for a year or more.

For the prevention of cytomegalovirus infection after transplantation: adults and adolescents 12 years of age and older - the recommended dose is 2 g 4 times / day, prescribed 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 the course of treatment can be extended.

Thus, the appearance of Valogard on the pharmaceutical market significantly expands the possibilities of the doctor and patient in choosing antiherpetic therapy.

Valacyclovir film-coated tablets 500 mg 10 pcs (Ozone-Atoll)

Registration Certificate Holder

ATOLL (Russia)

Dosage form

Medicine - Valacyclovir

Description

Film-coated tablets

white or almost white, round, biconvex.

1 tab.

valacyclovir hydrochloride 556.2 mg, which corresponds to the content of valacyclovir 500 mg

Excipients

: microcrystalline cellulose - 106.8 mg, povidone K25 - 12 mg, magnesium stearate - 5 mg.

Shell composition:

hypromellose - 11 mg, macrogol 4000 - 3 mg, titanium dioxide - 6 mg.

7 pcs. — cellular contour packages (1) — cardboard packs. 7 pcs. — contour cell packaging (2) — cardboard packs. 7 pcs. — cellular contour packages (3) — cardboard packs. 7 pcs. — contour cell packaging (4) — cardboard packs. 7 pcs. — contour cell packaging (5) — cardboard packs. 7 pcs. — contour cell packaging (6) — cardboard packs. 7 pcs. — contour cell packaging (7) — cardboard packs. 7 pcs. — contour cell packaging (8) — cardboard packs. 7 pcs. — contour cell packaging (9) — cardboard packs. 7 pcs. — contour cell packaging (10) — cardboard packs. 10 pieces. — cellular contour packages (1) — cardboard packs. 10 pieces. — contour cell packaging (2) — cardboard packs. 10 pieces. — cellular contour packages (3) — cardboard packs. 10 pieces. — contour cell packaging (4) — cardboard packs. 10 pieces. — contour cell packaging (5) — cardboard packs. 10 pieces. — contour cell packaging (6) — cardboard packs. 10 pieces. — contour cell packaging (7) — cardboard packs. 10 pieces. — contour cell packaging (8) — cardboard packs. 10 pieces. — contour cell packaging (9) — cardboard packs. 10 pieces. — contour cell packaging (10) — cardboard packs. 28 pcs. — cellular contour packages (1) — cardboard packs. 28 pcs. — contour cell packaging (2) — cardboard packs. 28 pcs. — cellular contour packages (3) — cardboard packs. 28 pcs. — contour cell packaging (4) — cardboard packs. 28 pcs. — contour cell packaging (5) — cardboard packs. 28 pcs. — contour cell packaging (6) — cardboard packs. 28 pcs. — contour cell packaging (7) — cardboard packs. 28 pcs. — contour cell packaging (8) — cardboard packs. 28 pcs. — contour cell packaging (9) — cardboard packs. 28 pcs. — contour cell packaging (10) — cardboard packs. 30 pcs. — cellular contour packages (1) — cardboard packs. 30 pcs. — contour cell packaging (2) — cardboard packs. 30 pcs. — cellular contour packages (3) — cardboard packs. 30 pcs. — contour cell packaging (4) — cardboard packs. 30 pcs. — contour cell packaging (5) — cardboard packs. 30 pcs. — contour cell packaging (6) — cardboard packs. 30 pcs. — contour cell packaging (7) — cardboard packs. 30 pcs. — contour cell packaging (8) — cardboard packs. 30 pcs. — contour cell packaging (9) — cardboard packs. 30 pcs. — contour cell packaging (10) — cardboard packs. 7 pcs. - cans (1) - cardboard packs. 10 pieces. - cans (1) - cardboard packs. 20 pcs. - cans (1) - cardboard packs. 28 pcs. - cans (1) - cardboard packs. 30 pcs. - cans (1) - cardboard packs. 40 pcs. - cans (1) - cardboard packs. 42 pcs. - cans (1) - cardboard packs. 50 pcs. - cans (1) - cardboard packs. 60 pcs. - cans (1) - cardboard packs. 100 pieces. - cans (1) - cardboard packs.

Indications

Treatment and prevention of infectious diseases caused by Herpes zoster.

Prevention of cytomegalovirus infection developing during organ transplantation.

Contraindications for use

Hypersensitivity to valacyclovir, acyclovir.

pharmachologic effect

Antiviral agent of the group of nucleoside analogues. Valacyclovir is the L-valine ester of acyclovir, thus being a prodrug.

After absorption into the blood, valacyclovir is almost completely converted to acyclovir under the influence of the liver enzyme valacyclovir hydrolase. Acyclovir, formed from valacyclovir, in turn, penetrates into cells affected by the virus, where, under the influence of the viral enzyme thymidine kinase, it is converted into monophosphate, then, under the influence of cellular kinases, into diphosphate and active triphosphate. Acyclovir triphosphate inhibits DNA polymerase and thus disrupts viral DNA replication. In addition, disruption of viral DNA replication may result from the incorporation of acyclovir into its structure. Thus, the high selectivity of valacyclovir for tissues affected by the virus is explained by the fact that stage I of the chain of phosphorylation reactions is mediated by an enzyme produced by the virus itself.

Active against Herpes simplex viruses types 1 and 2, Varicella zoster, cytomegalovirus, Epstein-Barr virus, human herpes virus 6.

Drug interactions

Acyclovir enters unchanged into the urine as a result of active tubular secretion. Any drugs that are prescribed concomitantly and compete for this elimination mechanism can cause an increase in the concentration of valacyclovir in plasma. Cimetidine and drugs that block tubular secretion, when prescribed after taking valacyclovir at a dose of 1 g, increase the AUC for acyclovir and reduce its renal clearance.

When co-administering acyclovir and the inactive metabolite mycophenolate mofetil (an immunosuppressant used in transplantation), an increase in the AUC of acyclovir and mycophenolate mofetil was observed.

When valaciclovir is used simultaneously with drugs that impair renal function (including cyclosporine, tacrolimus), renal function may deteriorate.

Dosage regimen

When taken orally, a single dose for adults is 0.25-2 g. The frequency of administration and duration of treatment depend on the indications.

Patients with severe renal impairment require dosage adjustment.

Side effect

From the digestive system:

nausea, discomfort, abdominal pain, vomiting, diarrhea, anorexia; rarely - transient increase in liver function tests.

From the side of the central nervous system:

headache, fatigue, dizziness, confusion, hallucinations;
rarely - disturbances of consciousness; in some cases - coma (usually in patients with impaired renal function or other predisposing factors). Allergic reactions:
rarely - rash, urticaria, itching, angioedema, anaphylaxis.

Other:

rarely - thrombocytopenia, shortness of breath, renal dysfunction, photosensitivity.

special instructions

Elderly patients need to increase their fluid intake during treatment.

Patients with renal impairment are at increased risk of developing neurological complications when taking valacyclovir.

Use with caution in patients with liver disease.

There is no clinical experience of use in children.

Use during pregnancy and breastfeeding

Restrictions during pregnancy - With caution. Restrictions when breastfeeding - With caution.

Adequate and strictly controlled studies of the safety of valacyclovir during pregnancy and lactation have not been conducted. Use in this category of patients is possible in cases where the expected benefit of therapy for the mother outweighs the potential risk for the fetus or infant.

It is known that acyclovir, which is a metabolite of valacyclovir, is excreted in breast milk in concentrations 0.6-4.1 times higher than its concentration in plasma. T1/2 of acyclovir from breast milk is 2.8 hours, which is comparable to T1/2 from blood plasma.

Use for renal impairment

Restrictions for impaired renal function - With caution.

Patients with renal impairment are at increased risk of developing neurological complications when taking valacyclovir.

Use for liver dysfunction

Restrictions for liver dysfunction - With caution.

Use with caution in patients with liver disease.

Use in elderly patients

Restrictions for elderly patients - Use with caution.

Elderly patients need to increase their fluid intake during treatment.

Use in children

Restrictions for children - Contraindicated.

There is no clinical experience of use in children.