Intimate antiviral products: we advise the buyer

HSV and HPV: similarities and differences

First of all, it is important to understand that the herpes simplex virus (HSV) and the human papillomavirus (HPV), which provoke herpes and human papillomavirus infections, respectively, are fundamentally different from each other.

"Galavit" for herpes virus infection helps:

• Pronounced elimination of viruses from the body
• Increasing the effectiveness of antiviral therapy
• Reducing the period of rashes and accelerating regeneration processes
• Increased duration of remission

In adults and adolescents over 12 years of age in complex therapy:

Suppositories

- 5 days, 1 suppository, then one every other day. Course - 2 packs of suppositories.

Sublingual tablets

— 10 days, 1 tablet 4 times a day. Then continue taking it every other day for 10 days, 4 tablets per day.

THERE ARE CONTRAINDICATIONS. YOU SHOULD CONSULT WITH A SPECIALIST.

HSV

Genital herpes is associated with infection with HSV type 1 or 2. According to statistics, the disease affects about 12% of the population [1]. Once it has penetrated the body, the virus “settles” in it forever - today there is no treatment method for the herpes virus that would allow one to finally get rid of the pathogen. Symptoms of genital herpes, which occur periodically during relapses, significantly reduce the quality of life. Interestingly, the frequency of new episodes of the disease depends on the type of virus: with HSV-1 infection, approximately 1 relapse is recorded per year, while with HSV-2 infection, their number can reach 6 or more [2].

Despite the fact that there is no specific treatment for HSV, a number of drugs can alleviate the condition during exacerbations. According to domestic and Western recommendations, oral antiviral agents for herpes based on acyclovir and valacyclovir are used for this purpose. However, in Russia local therapy is also recommended, which is not included in Western standards. Abroad, such methods are not included in the recommendations due to their lower activity compared to tablets [3].

HPV

The situation with papillomavirus infection (HPV) is somewhat different. It is considered the most common sexually transmitted disease in the world [4]. Most adults become infected with HPV at some point in their lives, but in 90% of cases the virus clears naturally within two years of infection. Otherwise, the infected person becomes a lifelong carrier.

Unfortunately, there is no cure for the human papillomavirus, just as there is no cure for the herpes simplex virus. However, the first, unlike the second, can be deadly: HPV types 16 and 18 are associated with malignant neoplasms - in particular, cervical cancer and some other tumors. The only effective drug treatment for human papillomavirus infection today is the eradication of condylomas, which are manifestations of clinical and subclinical forms of infection. For this purpose, a number of local antiviral drugs that have proven activity in studies are used in the treatment of human papillomavirus. At the same time, in domestic practice, doctors also prescribe drugs that have a dubious evidence base. Let's look at their advantages and disadvantages in more detail.

Valvir, 42 pcs., 500 mg, film-coated tablets

Inside

Regardless of food intake, tablets should be taken 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, it is considered most correct to prescribe the drug Valvir 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 Valvir 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 taking the first dose. When using this dosage regimen, the duration of treatment should not exceed 1 day, because Exceeding the duration of this course of treatment does not result in 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, incl. 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 CMV 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 Cl. 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 patient groups

Children.

The effectiveness of treatment with Valvir 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 Valvir should be adjusted accordingly. It is necessary to maintain adequate water and electrolyte balance.

Renal dysfunction.

It is recommended to reduce the dose of Valvir 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.

table 2

Dose adjustment of Valvir for use in adults and adolescents aged 12 to 18 years with impaired renal function

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 Valvir in children with creatinine Cl values ​​less than 50 ml/min/1.73 m2.

Additional information for the indications for the prevention of infections caused by CMV and diseases after solid organ transplantation.

It is necessary to frequently determine creatinine Cl, especially during periods when renal function changes rapidly, for example, immediately after transplantation or engraftment, and the dose of Valvir is adjusted in accordance with creatinine Cl values.

Additional information for the indications for the treatment of herpes zoster (Herpes zoster) and herpes zoster ophthalmicus.

Valvir 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 Valvir 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 the drug Valvir, however, clinical experience with these pathologies is limited.

Information on doses greater than 4000 mg/day for patients with infections caused by HSV and CMV is listed in the "Special Instructions" section.

Local immunomodulators for HPV and HSV

Among the “universal” drugs that can be prescribed for various viral infections - from common respiratory infections to herpes and human papillomavirus - are interferons. In particular, preparations of human recombinant interferon alpha-2b.

Interferon alpha-2b has antiviral, immunomodulatory and antiproliferative properties. It suppresses the replication of RNA and DNA viruses, enhances the activity of macrophages, and increases the cytotoxicity of lymphocytes to target cells. The use of drugs containing interferon alpha-2b is accompanied by an increase in the level of immunoglobulins type A and normalization of IgE [5]. However, these therapeutic effects are fully manifested when the drug is administered systemically.

when its high concentration in the blood is reached. It should be noted that quite powerful side effects can develop, including fever, loss of appetite, headaches, muscle pain, joint pain and many other adverse reactions.

Due to the specific safety profile, injectable interferon preparations are prescribed only in very serious cases, when the risk of side effects is justified - for example, in the treatment of hepatitis, a number of oncological diseases, etc. HSV and HPV infections do not apply to such situations and are not indications for systemic interferon administration. At the same time, the Russian Federation has registered a very impressive list of local forms of interferon alpha-2b, including ointments/creams for treating mucous membranes with genital herpes.

Theoretically, local interferon preparations should have all the advantages of injectable ones and not have their side effects, since local forms are either very slightly absorbed into the systemic circulation or do not penetrate into the blood at all. However, today there is no sufficiently reliable evidence of the effectiveness of interferons when applied topically. However, in domestic practice they are quite often prescribed as part of the complex treatment of recurrent genital herpetic infections.

Along with local forms containing only interferon alpha-2b, several combination drugs are also registered in the Russian Federation:

• Interferon alpha-2b + acyclovir + lidocaine, ointment. Indications: HSV.
• Interferon alpha-2b + taurine + benzocaine, vaginal and rectal suppositories, prescription. Indications: HSV, HPV. Taurine, according to the instructions, acts in combination as a reparative, antioxidant and anti-inflammatory component.

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High safety profile.

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The feasibility of using local forms of acyclovir for genital herpes is subject to serious doubts due to insufficient activity, which is confirmed in Western recommendations [3]. Interferon alpha-2b preparations, both mono- and combined, are available with or without a prescription, depending on the indications of the dispensing rules in the instructions for a particular drug. It is important to draw the visitor’s attention to the fact that the first-line treatment for HPV - oral forms of acyclovir and valacyclovir - must be prescribed by a doctor, so you should be advised to immediately consult a doctor.

Synthetic antiviral topical drugs

This group of drugs can be roughly divided into drugs used for genital herpes infection and antiviral drugs prescribed for the treatment of papillomas and condylomas associated with papillomavirus infection.

Local medications for genital herpes

Several drugs registered in the Russian Federation are used for the treatment and prevention of relapses of genital herpes.

Tromantadine

An antiviral drug for herpes, an adamantane derivative (similar to the well-known antiviral drugs rimantadine and amantadine). Inhibits the attachment of the virus to the surface of the cell membrane, preventing the pathogen from penetrating into the cell. Prevents cell fusion and makes it difficult for the virus to spread by changing the synthesis of glycoproteins [5]. Available in the form of a gel for external use, which can be applied to mucous membranes during exacerbation of HSV infection [5].

Vacation: without prescription.

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There is evidence of the development of a contact allergic reaction when using the drug [7].

Sodium aminodihydrophthalazindione

An immunomodulator capable of regulating the activity of innate and acquired immune cells, including macrophages, neutrophils and natural killer cells. At the same time, this antiviral drug against herpes increases the body's resistance to bacterial, viral and fungal infections, reducing their frequency, severity and duration (5). In addition, the drug normalizes the formation of antibodies and regulates the production of interferons, and also blocks the excessive synthesis of pro-inflammatory cytokines and reduces the level of oxidative stress (5).

Vacation: Without prescription

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High safety profile (5).

Azoximer bromide

A Russian drug supposedly exhibiting an immunostimulating effect. According to the instructions [5], it directly affects phagocytes and natural killer cells, stimulates the formation of antibodies and the synthesis of interferon, and exhibits antioxidant and detoxifying properties. In domestic practice, it is used for a wide range of diseases - from influenza to malignant neoplasms.

Azoximer bromide vaginal suppositories are used to prevent recurrence of genital herpes.

Vacation: without prescription.

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High safety profile. According to the manufacturer [5], no side effects have been reported.

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Azoximer bromide suppositories are not indicated for the treatment of active herpes!

Valvir 500 mg 10 pcs. pills

pharmachologic effect

Antiviral agent.

Composition and release form Valvir 500 mg 10 pcs. pills

Tablets - 1 tablet:

• active ingredient: valacyclovir hydrochloride hydrate 611.70 mg or 1223.40 mg, corresponding to valacyclovir 500 mg or 1000 mg;
• excipients: microcrystalline cellulose 59.60/119.20 mg, povidone-K30 24.50/49.00 mg, magnesium stearate 4.20/8.40 mg;
• film coating; Opadry white Y-5-7068 (hypromellose 3cP 7.35/14.70 mg, hyprolose 6.30/12.60 mg, titanium dioxide 4.20/8.40 mg, macrogol/PEG 400 2.10/4, 20 mg, hypromellose 50cP 1.05/2.10 mg) - 21/42 mg.

500 mg tablets: 10 or 14 tablets in PVC/Aluminum foil blisters. 1 blister (10 tablets each) or 3 blisters (14 tablets each) along with instructions for use in a cardboard pack with first-opening control.

Tablets 1000 mg: 7 tablets in PVC/Aluminum foil blisters. 1 or 4 blisters along with instructions for use in a cardboard pack with first-opening control.

Description of the dosage form

Film-coated tablets, 500 mg: oval, biconvex, white or almost white, marked VC2 on one side.

Film-coated tablets, 1000 mg: oval, biconvex, white or almost white, marked VC3 on one side.

Directions for use and doses

Inside.

Adults

Herpes zoster - 1000 mg 3 times a day for 7 days.

Herpes simplex - 500 mg 2 times a day. In case of relapses, the course should be 3 or 5 days. For the first severe episode, the duration of treatment can be increased to 10 days (for relapses, it is preferable to prescribe Valvir in the prodromal period or when the first symptoms of the disease appear, i.e. tingling, itching, burning).

For the treatment of labial herpes, it is effective to prescribe the drug at a dose of 2 g 2 times during the 1st day: the second dose should be taken approximately 12 hours (but not earlier than 6 hours) after the first dose (do not use this dosage regimen for more than 1 day as it has not been shown to provide additional clinical benefit).

Prevention of relapses of infections caused by the herpes simplex virus: in patients with preserved immunity - 500 mg 1 time per day; with very frequent relapses (10 or more per year) - 250 mg 2 times a day; for adult patients with immunodeficiency - 500 mg 2 times a day. Course duration is 4–12 months.

Prevention of infection with genital herpes of a healthy partner: infected heterosexual adults with preserved immunity and the number of exacerbations up to 9 per year - 500 mg 1 time per day for 1 year or more, every day with regular sexual activity, with irregular sexual intercourse, Valvir should be taken 3 days before expected sexual intercourse (data on the prevention of infection in other patient populations are not available).

Prevention of CMV infection: adults and adolescents over 12 years of age, 2 g 4 times a day (as soon as possible after transplantation). The course duration is 90 days, but in high-risk patients, treatment may be longer. It is recommended to reduce the dose of Valvir in patients with a significant decrease in renal function.

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

Patients on dialysis should be prescribed Valvir after the end of the hemodialysis session.

It is necessary to determine creatinine Cl frequently, especially during periods when renal function changes rapidly, for example immediately after transplantation or engraftment. In this case, the dose of Valvir is adjusted in accordance with creatinine Cl levels.

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

In elderly people, no dose adjustment is required, except for significant renal impairment. It is necessary to maintain adequate water and electrolyte balance.

Pharmacodynamics

In the human body, valacyclovir is quickly and completely converted into acyclovir and L-valine under the influence of valacyclovir hydrolase. Acyclovir in vitro has specific inhibitory activity against Herpes simplex viruses types 1 and 2, Varicella zoster and Epstein-Barr, CMV 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 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 cells affected by the virus. Partial phosphorylation selectivity is conserved in CMV and is mediated through the phosphotransferase gene product UL 97. Activation of acyclovir by a specific viral enzyme largely 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 analogue, is incorporated into viral DNA, which leads to obligate (complete) chain breakage, cessation of DNA synthesis and, consequently, blocking viral replication.

In patients with preserved immunity, Herpes simplex and Varicella zoster viruses with reduced sensitivity to valacyclovir are extremely rare (less than 0.1%), but can sometimes be detected in patients with severe immune disorders, for example with a bone marrow transplant, in those receiving chemotherapy for malignant neoplasms and in those infected with HIV.

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

Pharmacokinetics

Valacyclovir and acyclovir have similar pharmacokinetic parameters after oral administration.

Suction. After oral administration, valacyclovir is well absorbed from the gastrointestinal tract and is quickly and almost completely converted to acyclovir and L-valine. This transformation is catalyzed by the enzyme valacyclovir hydrolase, isolated from human liver.

After a single dose of 0.25–2 g of valacyclovir, Cmaxacyclovir in blood plasma in healthy volunteers with normal renal function averages 10–37 µmol/l (2.2–8.3 µg/ml), and the median time to reach this concentration is 1 –2 hours

When taking valacyclovir in a dose of 1 g, the bioavailability of acyclovir is 54% and does not depend on food intake.

Cmax of valacyclovir 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 - about 15%. Acyclovir is quickly distributed throughout the tissues of the body, especially to the liver, kidneys, muscles, and lungs. It also penetrates vaginal secretions, cerebrospinal fluid and herpetic vesicle fluid.

Excretion. In patients with normal renal function, T1/2 of acyclovir after a single dose and repeated use 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% is excreted unchanged. drug.

Pharmacokinetics in special clinical situations

In patients with end-stage renal failure, T1/2 of acyclovir is approximately 14 hours.

The pharmacokinetics of acyclovir are not significantly affected in patients infected with Herpes simplex and Varicella zoster viruses, as well as in elderly patients and patients with cirrhosis.

In patients with severely impaired renal function, Cmax of acyclovir is approximately 2 times greater than in healthy patients and T1/2 of acyclovir is increased by 5 times.

Acyclovir, the main metabolite of valacyclovir, is excreted in breast milk.

After administration of valacyclovir orally at a dose of 500 mg, the Cmax of acyclovir in breast milk was 0.5–2.3 times (on average 1.4 times) higher than its corresponding concentration in maternal plasma. The ratio of AUC of acyclovir found in breast milk to AUC of acyclovir in maternal plasma was 1.4–2.6 (mean 2.2). The average concentration of acyclovir in breast milk is 2.24 mcg/ml. When the mother is given valaciclovir at a dose of 500 mg twice a day, the child will be exposed to the same amount of acyclovir as if it was taken orally at a dose of about 0.61 mg/kg/day. T1/2 of acyclovir from breast milk is the same as from blood plasma. Valacyclovir in unchanged form is not detected in maternal plasma, breast milk or infant urine.

In late pregnancy, the steady-state daily AUC after taking 1 g of valacyclovir was approximately 2 times greater than that when taking acyclovir at a dose of 1.2 g / day. During pregnancy, the pharmacokinetic characteristics of valacyclovir do not change.

When taking valacyclovir at a dose of 1 and 2 g, the distribution and pharmacokinetic parameters of valacyclovir in HIV-infected patients are not affected compared to healthy individuals.

In organ transplant recipients receiving valacyclovir 2 g 4 times daily, the Cmax of acyclovir is equal to or greater than that of healthy volunteers receiving the same dose of the drug, and their daily AUC values ​​​​are significantly higher.⁠

Indications for use Valvir 500 mg 10 pcs. pills

• treatment of herpes zoster;
• treatment and prevention of recurrent infections of the skin and mucous membranes caused by the herpes simplex virus (including newly diagnosed and recurrent genital herpes);
• treatment of labial herpes;
• reduction of genital herpes infection in a healthy partner if the drug is taken as a suppressive therapy in combination with safe sex;
• prevention of CMV infection that occurs during organ transplantation (reduces the severity of acute graft rejection in patients with kidney transplants, the development of opportunistic infections and other viral infections caused by Herpes simplex and Varicella zoster viruses) in adults and children over 12 years of age.

Contraindications

• hypersensitivity to valacyclovir, acyclovir and other components of the drug;
• clinically pronounced forms of HIV infection with a CD4+ lymphocyte count of less than 100/μl;
• bone marrow transplantation;
• kidney transplantation;
• children's age (up to 12 years for CMV infection; up to 18 years for other indications).

With caution: patients with renal failure; patients with clinically significant forms of HIV infection; simultaneous use of nephrotoxic drugs.

Application of Valvir 500 mg 10 pcs. pills during pregnancy and breastfeeding

Use during pregnancy is possible if the expected effect of therapy for the mother exceeds the potential risk to the fetus (there is insufficient information on use during pregnancy).

Acyclovir, the main metabolite of valacyclovir, is excreted in breast milk. During therapy with valacyclovir, breastfeeding is possible if the expected effect of therapy for the mother outweighs the potential risk for the child.

special instructions

500 mg tablets: oval, biconvex tablets, white or off-white, marked VC2 on one side.

Overdose

Currently, there is insufficient data on valacyclovir overdose.

Symptoms: a single dose of acyclovir up to 20 g, which was partially absorbed from the gastrointestinal tract, was not accompanied by a toxic effect of the drug. When taking ultra-high doses of acyclovir orally for several days, nausea, vomiting, headache, and confusion developed; with intravenous administration - an increase in serum creatinine concentration, the development of renal failure, confusion, hallucinations, agitation, convulsions, coma.

Treatment: Patients should be under close medical supervision for signs of toxicity. Hemodialysis significantly enhances the removal of acyclovir from the blood and can be considered the treatment of choice in the management of patients with an overdose of valacyclovir.

Side effects Valvir 500 mg 10 pcs. pills

The most common adverse reactions with valacyclovir are headache and nausea; more serious adverse reactions are thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, acute renal failure and neurological disorders.

Adverse reactions are listed below according to the classification by main systems and organs and by frequency of occurrence: very often - ≥1/10; often - ≥1/100 or

From the gastrointestinal tract: often - nausea; rarely - abdominal discomfort, incl. abdominal pain; vomiting, diarrhea; very rarely - reversible abnormalities in liver function tests, which are sometimes regarded as manifestations of hepatitis.

From the blood and lymphatic system: very rarely - leukopenia (mainly in patients with reduced immunity), thrombocytopenia.

From the immune system: very rarely - anaphylaxis.

Mental disorders and disorders of the nervous system: often - headache; infrequently - agitation, including aggressive behavior; rarely - dizziness, confusion, hallucinations, decreased mental abilities; very rarely - agitation, tremor, ataxia, dysarthria; psychotic symptoms including mania; depression, seizures, encephalopathy, coma.

These symptoms are reversible and are usually observed in patients with impaired renal function or against the background of other diseases. In organ transplant patients receiving high doses of valacyclovir (8 g/day) for the prevention of CMB infection, neurological reactions develop more often than when taking lower doses.

From the respiratory system and mediastinum: infrequently - dyspnea.

From the skin and subcutaneous tissue: infrequently - rashes, including manifestations of photosensitivity; rarely - itching.

Allergic reactions: very rarely - urticaria, angioedema.

From the urinary system: infrequently - hematuria (often associated with other renal disorders); rarely - renal dysfunction; very rarely - acute renal failure, renal colic (may be associated with impaired renal function). Precipitation of acyclovir crystals in the lumen of the renal tubules is possible. It is necessary to maintain an adequate drinking regime during treatment.

Other: In patients with severe immune impairment, especially in patients with advanced acquired immune deficiency syndrome, receiving high doses of valacyclovir (8 g/day) for a long time, cases of renal failure, microangiopathic hemolytic anemia and thrombocytopenia (sometimes in combination) have been observed. ). Similar complications have been noted in patients with the same diseases but not receiving valacyclovir.

It is not possible to determine the frequency of occurrence of some adverse reactions based on the available data.

From the senses: visual impairment.

From the hematopoietic organs: neutropenia, aplastic anemia, leukoplastic vasculitis, thrombotic thrombocytopenic purpura.

From the skin: erythema multiforme.

Laboratory indicators: decreased Hb level, hypercreatinemia.

Other: dysmenorrhea, arthralgia, nasopharyngitis, respiratory tract infections, facial swelling, increased blood pressure, tachycardia, fatigue; additionally in children - fever, dehydration, rhinorrhea.⁠

Drug interactions

Concomitant use of valacyclovir with nephrotoxic drugs, including aminoglycosides, organic platinum compounds, iodinated contrast agent, methotrexate, pentamidium, foscarnet, cyclosporine and tacrolimus should be carried out with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function .

No clinically significant interactions have been established.

Cimetidium and probenecid after taking 1 g of valacyclovir increase the AUC of acyclovir, reducing its renal clearance (however, dose adjustment of valacyclovir is not required due to the wide therapeutic index of acyclovir).

Caution must be exercised in the case of simultaneous use of valacyclovir in high doses (4 g / day) and drugs that compete with acyclovir for the elimination route (the latter is eliminated in the urine unchanged as a result of active tubular secretion), since there is a potential threat of increased plasma concentrations one or both drugs or their metabolites.

With simultaneous use of acyclovir with mycophenolate mofetil, an increase in the AUC of acyclovir and the inactive metabolite mycophenolate mofetil was observed.

Topical antiviral drugs for the treatment of HPV (papillomavirus)

Some topical antiviral drugs active against papillomaviruses, in contrast to a number of drugs that help against the herpes virus, have a strong evidence base and are used throughout the world to treat manifestations of HPV - in particular, condylomas.

Imiquimod

An immune response modifier that does not have an antiviral effect. It exhibits activity due to the ability to induce the production of interferon-alpha and other cytokines. Indicated for the treatment of genital warts in the urogenital area [5].

Release: by prescription.

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Solid evidence base. The drug definitely reduces the viral load. The use of imiquimod cream 5% 3 times a week at night for 16 weeks has been proven to be effective and safe for the treatment of condylomas. The relapse rate is estimated to be low [8]. Imiquimod is recommended for the treatment of genital warts by the authoritative American regulator FDA [8].

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When applying imiquimod, itching and pain are observed in more than 10% of cases [5], which the buyer should be warned about.

Local antiviral herbal remedies

Ammonium glycyrrhizinate

The active component of the drug, activated glycyrrhizic acid, is obtained from licorice root. It has a complex immunostimulating, antiviral, anti-inflammatory, antipruritic effect. Glycyrrhizic acid interrupts the replication of a number of DNA and RNA viruses, including herpes simplex virus, human papillomavirus, and cytomegalovirus [5].

Indicated as a drug for the treatment of human papillomavirus infection and herpes simplex virus, including infection with oncogenic viruses. Available in the form of a spray, which is sprayed onto the mucous membranes and affected areas of the skin.

Vacation: without prescription.

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It has a wide range of indications, including the prevention and treatment of vulvovaginal candidiasis, discomfort in the genital area. Can be used during pregnancy and breastfeeding; well tolerated.

Podophyllotoxin

The active component of podophyllin, a derivative of plant extracts isolated from the rhizomes with roots of Podophyllum thyroid - a plant of the barberry family. It has pronounced antitumor and antiviral properties and has a cytotoxic effect. When used externally, it cauterizes and mummifies condylomas. It is used as a drug for local treatment of human papillomavirus. Available in the form of a solution for the treatment of genital warts [8].

Release: by prescription.

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Proven effect. According to research, a 0.5% solution of podophyllotoxin reduces the number of anogenital warts from 6.3 to 1.1, destroying about 70% of formations [8].

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Care must be taken when using - contact with healthy skin can lead to ulceration. Local reactions during use, allergic reactions. The physician, when dispensing this antiviral drug for papillomas and condylomas, must draw the client’s attention to this feature and remind him that the drug should be stored out of the reach of children.

Tetrahydroxyglucopyranosylxanthene

Russian drug. The active component is isolated from the Alpine kopek plant or the yellow kopek plant.

According to the instructions, it has antiviral activity against HSV-1 and HSV-2, as well as cytomegalovirus and some other DNA-containing viruses. In addition, the drug presumably activates cellular and humoral immunity, inhibits the growth of a number of bacteria and pathogenic protozoa, including Trichomonas, and also has a moderate anti-inflammatory effect. Used in the form of an ointment as part of the combined treatment of acute and recurrent forms of herpes, including genital herpes [5].

Vacation: without prescription.

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Favorable safety profile, the ability to be used as part of complex treatment.

Polysaccharides of Solanum tuberosum shoots

A Russian prescription drug, the active component is obtained from the shoots of tuberous nightshade. According to the instructions, it exhibits an antiviral effect against HSV-1 and HSV-2, promotes the induction of interferons and increases the immune response [5]. It should be noted that the pharmacokinetic properties of the drug have not been studied. Vaginal suppositories are used in complex therapy of genital herpes.

Vacation: without prescription.

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High safety profile. Side effects are rare.

Desmodium canada herb extract

An antiviral drug for herpes of plant origin, created from a dry extract of the herb Desmodium canadensis. According to the instructions, it exhibits antiviral activity against herpes viruses and stimulates the production of interferon [5]. The ointment is indicated for use in acute and recurrent forms of herpes, including urogenital.

Vacation: without prescription.

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High safety profile - no side effects identified.

Hyporamine extract

Russian development based on sea buckthorn leaf extract. According to the instructions, it is active against herpes simplex viruses, cytomegaloviruses and some others [5]. An ointment containing hyporamin extract is indicated for the treatment and prevention of episodes of herpes, including genital herpes.

Vacation: without prescription.

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High safety profile; Possibility of use during pregnancy and lactation (after consultation with a doctor).

Valvir

Antiviral drug. In the human body, valacyclovir is quickly and completely converted into acyclovir and L-valine under the influence of valacyclovir hydrolase.

Acyclovir in vitro has specific inhibitory activity against Herpes simplex viruses types 1 and 2, Varicella zoster and Epstein-Barr, cytomegalovirus (CMV) and human herpes virus type 6. Acyclovir inhibits the synthesis of viral DNA immediately after phosphorylation and conversion to the 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 cells affected by the virus. Partial phosphorylation selectivity is conserved in CMV and is mediated through the phosphotransferase gene product UL 97. Activation of acyclovir by a specific viral enzyme largely 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 analogue, is incorporated into viral DNA, which leads to obligate (complete) chain breakage, cessation of DNA synthesis and, consequently, blocking viral replication.

In patients with preserved immunity, Herpes simplex and Varicella zoster viruses with reduced sensitivity to valacyclovir are extremely rare (less than 0.1%), but can sometimes be detected in patients with severe immune disorders, for example, with a bone marrow transplant, in those receiving chemotherapy for malignant diseases. neoplasms and in those infected with HIV.

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

Pharmacokinetics

Valacyclovir and acyclovir have similar pharmacokinetic parameters after oral administration.

Suction

After oral administration, valacyclovir is well absorbed from the gastrointestinal tract and is quickly and almost completely converted to acyclovir and L-valine. This transformation is catalyzed by the enzyme valacyclovir hydrolase, isolated from human liver.

After a single dose of 0.25-2 g of valacyclovir, the Cmax of acyclovir in healthy volunteers with normal renal function averages 10-37 µmol/l (2.2-8.3 µg/ml), and the median time to reach this concentration is 1-2 hours.

When taking valacyclovir in a dose of 1 g, the bioavailability of acyclovir is 54% and does not depend on food intake.

The Cmax of valacyclovir 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 - about 15%. Acyclovir is quickly distributed throughout the tissues of the body, especially to the liver, kidneys, muscles, and lungs. It also penetrates into vaginal secretions, cerebrospinal fluid and herpetic vesicle fluid.

Removal

In patients with normal renal function, T1/2 of acyclovir after taking a single dose and repeated use is approximately 3 hours. Valaciclovir is excreted in the urine, mainly in the form of acyclovir (more than 80% of the dose) and its metabolite 9-carboxymethoxymethylguanine, excreted unchanged less than 1% of the drug.

Pharmacokinetics in special clinical situations

In patients with end-stage renal failure, T1/2 of acyclovir is approximately 14 hours.

The pharmacokinetics of acyclovir are not significantly affected in patients infected with Herpes simplex and Varicella zoster viruses, as well as in elderly patients and patients with cirrhosis.

In patients with severely impaired renal function, the Cmax of acyclovir is approximately 2 times greater than in healthy patients and the T1/2 of acyclovir increases by 5 times.

Acyclovir, the main metabolite of valacyclovir, is excreted in breast milk. After administration of valacyclovir orally at a dose of 500 mg, the Cmax of acyclovir in breast milk was 0.5-2.3 times (on average 1.4 times) higher than its corresponding concentration in maternal plasma. The ratio of AUC of acyclovir found in breast milk to AUC of acyclovir in maternal plasma was 1.4-2.6 (average 2.2). The average concentration of acyclovir in breast milk is 2.24 mcg/ml. When the mother is given valaciclovir at a dose of 500 mg twice daily, the child will be exposed to the same amount of acyclovir as if it was taken orally at a dose of about 0.61 mg/kg/day. T1/2 of acyclovir from breast milk is the same as from blood plasma. Valacyclovir in unchanged form is not detected in maternal plasma, breast milk or infant urine.

In late pregnancy, the steady-state daily AUC after taking 1 g of valacyclovir was approximately 2 times greater than that when taking acyclovir at a dose of 1.2 g/day. During pregnancy, the pharmacokinetic characteristics of valacyclovir do not change.

Taking valacyclovir at a dose of 1 g and 2 g does not affect the distribution and pharmacokinetic parameters of valacyclovir in HIV-infected patients compared to healthy individuals.

In organ transplant recipients receiving valacyclovir at a dose of 2 g 4 times / day, the Cmax of acyclovir is equal to or greater than that in healthy volunteers receiving the same dose of the drug, and their daily AUC values ​​​​are significantly higher.