Valtrex tablets p/o 500mg №10×1

Name:
Valtrex.
Description:
: White film-coated tablet, white or almost white tablet core. Biconvex, oblong, without notch, engraved on one side with the inscription GX CF1. The main active ingredient is Valaciclovir. Release form Tablets. Dosage 500mg. Special instructions Studies to assess the effect of taking valaciclovir on the ability to drive a car and work with mechanisms have not been conducted. When determining the patient’s ability to drive a car and work with machinery, it is necessary to take into account the clinical condition of the patient and the profile of possible adverse reactions after taking Valtrex. Pharmacological action Antiviral agents for systemic use. Nucleosides and nucleotides, excluding reverse transcriptase inhibitors. ATX code: J05AB11 Pharmacodynamics Mechanism of action: Valaciclovir, an antiviral agent, is the L-valine ester of aciclovir. Acyclovir is an analogue of the purine nucleoside guanine. In the human body, valacyclovir is rapidly and almost completely converted to acyclovir and valine, probably by the enzyme valacyclovir hydrolase. Acyclovir has in vitro specific inhibitory activity against herpes simplex viruses (HSV) types 1 and 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) 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 requires the activity of virus-specific enzymes. For HSV, VZV, and EBV, this enzyme is viral thymidine kinase, which is present only in virus-infected cells. In part, the selectivity of phosphorylation is maintained in cytomegalovirus indirectly through the product of the UL 97 phosphotransferase gene. This need for 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 analog, is integrated into viral DNA, which leads to obligate chain break, DNA synthesis cessation and, consequently, to blocking of virus replication. Aciclovir resistance is usually due to thymidine kinase deficiency, resulting in overspread of the virus in the host. The decrease in sensitivity to acyclovir is due to the appearance of virus strains with a violation of the structure of viral thymidine kinase or DNA polymerase. The virulence of these varieties of the virus resembles that of its wild strain. When monitoring patients treated with acyclovir for treatment or prophylaxis, clinical strains of HSV and VZV with reduced sensitivity to acyclovir were extremely rarely detected in immunocompetent patients and in rare cases in patients with severely impaired immunity, for example, after organ or bone marrow transplantation, in patients receiving chemotherapy about malignant neoplasms and in HIV-infected people. Pharmacokinetics Valacyclovir is a prodrug of acyclovir. The bioavailability of acyclovir derived from valacyclovir is 3.3 to 5.5 times greater than that observed for oral acyclovir. After oral administration, valacyclovir is well absorbed from the gastrointestinal tract, quickly and almost completely turning into acyclovir and valine. This conversion is probably catalyzed by the enzyme valacyclovir hydrolase isolated from the human liver. When taking valacyclovir at a dose of 1000 mg, the bioavailability of acyclovir is 54% and does not depend on food intake. The pharmacokinetics of valaciclovir is not dose proportional. The rate and extent of absorption decreases with increasing dose, which leads to a disproportionate increase in Cmax in the therapeutic dose range and to a decrease in bioavailability when taking a dose above 500 mg. The pharmacokinetic parameters of acyclovir following a single dose of valacyclovir at a dose of 250-2000 mg in healthy volunteers with normal renal function are presented in the table below. Pharmacokinetic parameters of acyclovir 250 mg (N = 15) 500 mg (N = 15) 1000 mg (N = 15) 2000 mg (N = 8) h) 0.75 (0.75-1-5) 1.0 (0.75-2.5) 2.0 (0.75-3.0) 2.0 (1.5-3.0) AUC h. mcg/ml 5.50 ± 0.82 11.1 ± 1.75 18.9 ± 4.51 29.5 ± 6.36 Cmax = peak concentration ; Tmax = time to peak concentration; AUC = area under the concentration-time curve. The Cmax and AUC values show the mean ± standard deviation. The Tmax value shows the median and range. The peak concentration of valaciclovir in unchanged form in plasma is only 4% of the peak concentration of acyclovir, the median time to reach it is 30-100 minutes after a dose, after 3 hours the concentration level is at or below the limit of quantitation. Valacyclovir and acyclovir have similar pharmacokinetic parameters after single and multiple doses. Herpes zoster, herpes simplex, and HIV infection do not cause significant changes in the pharmacokinetics of valaciclovir and aciclovir following oral valaciclovir administration compared with healthy adults. In organ transplant recipients receiving valacyclovir at a dose of 2000 mg 4 times a day, the peak concentration 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. Distribution. The degree of binding of valaciclovir to plasma proteins is very low (only 15%). Penetration into the cerebrospinal fluid (CSF), determined by the ratio of AUC in CSF to AUC in blood plasma, does not depend on the state of liver function and is about 25% for acyclovir and the 8-hydroxyacyclovir metabolite (8-OH-ACV) and about 2.5 % for the metabolite 9-(carboxymethoxy)methylguanine (CMMG). Biotransformation. After oral administration, valaciclovir is converted to acyclovir and L-valine via first pass metabolism in the intestine and/or hepatic metabolism. To a small extent, acyclovir is converted to the CMMG metabolite by alcohol and aldehyde dehydrogenase and to 8-OH-ACV by aldehyde oxidase. About 88% of the total plasma exposure of the drug is due to acyclovir, 11% to CMMG and 1% to 8-OH-ACV. Neither valaciclovir nor acyclovir is metabolized by cytochrome P450 enzymes. Withdrawal. Valacyclovir is excreted from the body in the urine mainly as acyclovir (more than 80% of the dose) and the acyclovir metabolite CMMG (about 14% of the dose). The 8-OH-ACV metabolite is found in the urine only in small amounts (<2% of the dose). Less than 1% of the drug is eliminated unchanged. In patients with normal renal function, the plasma half-life of acyclovir after single and multiple doses of valaciclovir is about 3 hours. Special groups of patients. Patients with impaired renal function. Excretion of acyclovir correlates with renal function, the exposure of acyclovir increases with increasing severity of renal failure. In patients with end-stage renal disease, the average half-life of acyclovir after taking valaciclovir is about 14 hours, compared with 3 hours in patients with normal renal function (see section "Method of application and dosage"). Steady-state plasma and cerebrospinal fluid concentrations of acyclovir and its metabolites (CMMG and 8-OH-ACV) were assessed following multiple doses of valaciclovir in 6 patients with normal renal function (mean creatinine clearance 111 ml/min, range 91–144 ml/min), who received 2000 mg every 6 hours, and in 3 patients with severe renal insufficiency (mean creatinine clearance 26 ml / min, range 17-31 ml / min) who received 1500 mg every 12 hours. Plasma and cerebrospinal fluid concentrations of acyclovir, CMMG, and 8-OH-ACV were on average 2, 4, and 5-6 times higher, respectively, in patients with severe renal insufficiency compared with patients with normal renal function. Patients with impaired liver function. Pharmacokinetic data indicate that abnormal liver function reduces the rate of conversion of valacyclovir to acyclovir, but does not affect the degree of conversion. The half-life of acyclovir remains unchanged. Pregnant women. A study of the pharmacokinetics of valaciclovir and aciclovir in women in late pregnancy indicates that pregnancy does not affect the pharmacokinetics of valaciclovir. Excretion into breast milk. After oral administration of valacyclovir at a dose of 500 mg, the maximum concentrations of acyclovir (Cmax) in breast milk ranged from 0.5 to 2.3 times the corresponding serum concentration of acyclovir in the mother. The average concentration of acyclovir in breast milk was 2.24 μg / ml (9.95 μmol / l). When the mother takes valacyclovir at a dose of 500 mg 2 times a day, a breast-fed child will receive a daily oral dose of acyclovir equal to 0.61 mg / kg. The half-life of acyclovir in breast milk was similar to that in serum. Unchanged valaciclovir was not detected in the mother's serum, milk or urine of the child. Indications for use Infections caused by the Varicella zoster virus - herpes zoster. Treatment of herpes zoster and ophthalmic herpes in immunocompetent adults, as well as treatment of herpes zoster in adults with mild or moderate immunosuppression (see Precautions section). Infections caused by the herpes simplex virus (HSV). Treatment and suppression of infections of the skin and mucous membranes caused by HSV, including: treatment of newly diagnosed genital herpes in immunocompetent adults and adolescents and in immunocompromised adults; treatment of recurrence of genital herpes in immunocompetent adults and adolescents and in immunocompromised adults; prevention (suppression - recurrence of genital herpes in immunocompetent adults and adolescents and in immunocompromised adults; treatment of herpes labialis. . Clinical studies have not been conducted in HSV-infected patients with reduced immunity due to causes other than HIV infection. Cytomegalovirus (CMV) infection Prevention of cytomegalovirus (CMV) infection following solid organ transplantation in adults and adolescents (see Precautions section). Dosage and administration Treatment of herpes zoster and ophthalmic herpes. Treatment should begin as early as possible, immediately after the diagnosis of herpes zoster. There are no data on treatment initiated more than 72 hours after rash onset. immunocompetent adults. Valtrex is prescribed at a dose of 1000 mg 3 times a day for 7 days (total daily dose is 3000 mg). The dose should be reduced depending on the creatinine clearance (see section "Doses in renal failure" below). Immunocompromised adults. Valtrex is prescribed at a dose of 1000 mg 3 times a day for at least 7 days (total daily dose is 3000 mg) and within 2 days after the formation of crusts. The dose should be reduced depending on the creatinine clearance (see section "Doses in renal failure" below). Antiviral therapy is recommended in immunosuppressed patients who seek medical attention within one week of the vesicle formation period or anytime before complete crusting. Treatment of infections caused by HSV in adults and adolescents (from 12 years of age). Immunocompetent adults and adolescents (from 12 years of age). Valtrex is prescribed at a dose of 500 mg 2 times a day (total daily dose is 1000 mg). The dose should be reduced depending on the creatinine clearance (see section "Doses in renal failure" below). For recurrent episodes, treatment should be continued for 3 to 5 days. In primary cases, which may be more severe, the duration of treatment may be extended up to 10 days. Treatment should begin as soon as possible. In case of relapses of HSV, it is considered ideal to prescribe Valtrex in the prodromal period or immediately after the onset of the first symptoms of the disease. Valtrex may prevent the development of lesions if therapy is started at the first signs and symptoms of HSV recurrence. Treatment of labial herpes. For the treatment of labial herpes, the administration of valacyclovir to adults and adolescents at a dose of 2000 mg twice for 1 day is effective. The second dose should be taken approximately 12 hours (but not earlier than 6 hours) after the first dose. The dose should be reduced depending on the creatinine clearance (see section "Doses in renal failure" below). When using this dosing regimen, the duration of treatment should not exceed 1 day, since, as it has been shown, this excess does not provide additional clinical benefits. Therapy should be started at the earliest symptoms of herpes labialis (tingling, itching, burning). Immunocompromised adults. For the treatment of HSV in patients with reduced immunity, Valtrex is prescribed at a dose of 1000 mg 2 times a day for at least 5 days after assessing the severity of the clinical condition and the patient's immune status. In primary cases, which may be more severe, the duration of treatment may be extended up to 10 days. Treatment should begin as early as possible. The dose should be reduced depending on the creatinine clearance (see section "Doses in renal failure" below). To achieve the maximum clinical effect, treatment should be started within the first 48 hours after the onset of symptoms. Damage progression should be carefully monitored. Prevention (suppression) of recurrence of infections caused by HSV in adults and adolescents from 12 years of age. Immunocompetent adults and adolescents from 12 years of age. In immunocompetent patients, Valtrex is prescribed at a dose of 500 mg once a day. In patients with very frequent relapses (10 or more per year in the absence of therapy), an additional effect can be achieved by prescribing Valtrex at a daily dose of 500 mg divided into 2 doses (250 mg 2 times a day). The dose should be reduced depending on the creatinine clearance (see section "Doses in renal failure" below). Treatment should be reviewed after 6-12 months of therapy. Immunocompromised adults. The recommended dose of Valtrex is 500 mg twice daily. The dose should be reduced depending on the creatinine clearance (see section "Doses in renal failure" below). Treatment should be reviewed after 6-12 months of therapy. Prevention of CMV infection in adults and adolescents (from 12 years of age). It is recommended to prescribe Valtrex at a dose of 2000 mg 4 times a day, as early as possible after transplantation. The dose should be reduced depending on the creatinine clearance (see section "Doses in renal failure" below). The duration of treatment is 90 days, but in patients at high risk, treatment may be longer. Special groups of patients. Patients with impaired renal function. Valtrex should be used with caution in patients with renal insufficiency. Adequate fluid and electrolyte balance must be maintained. The dose of Valtrex is recommended to be reduced in patients with impaired renal function (see doses for renal insufficiency in the table). Therapeutic indications Creatinine clearance ml/min Dose Valtrex* Varicella zoster infections Treatment of herpes zoster in immunocompetent and immunocompromised adults ≥50 30-49 10-29 <10 1000 mg 3 times a day 1000 mg 2 times a day 1000 mg once daily 500 mg once daily Herpes simplex virus (HSV) infections Treatment of HSV infection - immunocompetent adults and adolescents - immunocompromised adults ≥30 <30 ≥30 <30 500 mg bid 500 mg 1000 mg once daily 1000 mg 2 times daily 1000 mg once daily Treatment of herpes labialis in immunocompetent adults and adolescents (alternative daily dosing regimen) ≥50 30-49 10-29 <10 2000 mg twice daily 1000 mg twice within 1 day 500 mg twice within 1 day 500 mg once Suppression of HSV infection - immunocompetent adults and adolescents - immunocompromised adults ≥30 <30 ≥30 <30 500 mg once a day** 250 mg once a day 500 mg 2 times a day and 500 mg once a day Cytomegalovirus infections Prevention of CMV infection after solid organ transplantation in adults and adolescents 4 times a day 1500 mg 3 times a day 1500 mg 2 times a day 1500 mg 1 time per day * For patients on intermittent hemodialysis, it is recommended to use Valtrex after the end of the hemodialysis session on the days of the procedure. **For the suppression of HSV infections in immunocompetent patients with a history of at least 10 relapses per year, improvement may be achieved with a dose of 250 mg twice daily. In patients on intermittent hemodialysis, Valtrex should be administered after the end of the hemodialysis session. It is necessary to determine creatinine clearance frequently, especially during periods when renal function changes rapidly, for example, immediately after transplantation or graft engraftment, while the dose of Valtrex ™ is adjusted in accordance with creatinine clearance. 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), dose adjustment of Valtrex is not required. Pharmacokinetic data in adult patients with severe liver dysfunction (decompensated cirrhosis), with impaired synthetic liver function and the presence of porto-caval anastomoses also do not indicate the need for dose adjustment of Valtrex, however, the experience of its clinical use in this pathology is limited. For information on the use of higher doses (4000 mg or more per day), see the "Precautions" section. Children. The effectiveness of Valtrex in children under 12 years of age has not been evaluated. Elderly patients. It is necessary to take into account the possibility of impaired renal function in elderly patients and adjust the dose accordingly (see section "Doses in renal failure" above). Maintain adequate hydration. Pregnancy and lactation Pregnancy: There are limited data on the use of valaciclovir and relatively more data on the use of aciclovir during pregnancy from pregnancy registries in women treated with valaciclovir or aciclovir (the active metabolite of valaciclovir) orally or intravenously: 111 and 1246 women respectively (29 and 756 pregnant women, respectively, received valacyclovir or acyclovir in the first trimester of pregnancy), and post-marketing data showed no increase in birth defects in children or feto/neonatal toxicity. Animal studies have not revealed reproductive toxicity of valaciclovir. Valtrex should only be used during pregnancy if the potential benefit outweighs the potential risk. Lactation: Aciclovir, the main metabolite of valaciclovir, is excreted in breast milk. However, when taking valaciclovir at therapeutic doses, no effect on breastfed infants is expected, since the dose received by the child with breast milk is less than 2% of the therapeutic dose of intravenous acyclovir for the treatment of neonatal herpes ( see section "Pharmacokinetics"). Valaciclovir should be used with caution during lactation and only when clinically indicated. Fertility: Orally administered valaciclovir did not impair fertility in rats. With parenteral administration of high doses of acyclovir in rats and dogs, testicular atrophy and aspermatogenesis were observed. Studies of the effect of valaciclovir on human fertility have not been conducted, however, in 20 patients who took 400 to 1000 mg of acyclovir daily for 6 months, no changes were observed in the number of spermatozoa, their motility and morphology. Precautions Degree of hydration of the body. In patients at risk of dehydration, especially elderly patients, adequate fluid replacement should be ensured. Use in renal failure and elderly patients. Acyclovir is eliminated by renal clearance, so the dose of valaciclovir should be reduced in patients with impaired renal function (see section "Method of application and dosage"). In elderly patients, a decrease in renal function is possible, and therefore it is necessary to consider dose reduction. Elderly patients and patients with renal insufficiency have an increased risk of developing neurological side effects, so these effects must be carefully monitored. In the reports, these adverse reactions were mostly reversible after discontinuation of treatment (see section "Side Effects"). The use of higher doses of Valtrex in liver failure and liver transplantation. There are no data on the use of the drug Valtrex in higher doses (4000 mg or more per day) in patients with liver disease. Special studies on the effect of Valtrex in liver transplantation have not been conducted, therefore, daily doses exceeding 4000 mg should be administered with caution to such patients. Use for the treatment of herpes zoster. Careful monitoring of clinical efficacy is necessary, especially in immunocompromised patients. Consideration should be given to intravenous antiviral therapy if the effectiveness of oral therapy is insufficient. Treatment of patients with complicated forms of herpes zoster, i.e. with involvement of internal organs, disseminated herpes zoster, motor neuropathy, encephalitis and cerebrovascular complications, should be carried out using intravenous antiviral therapy. In addition, immunocompromised patients with herpes ophthalmos or those at increased risk of disease dissemination or visceral involvement should be treated with intravenous antiviral therapy. transmission of genital herpes. If symptoms are present, patients should be warned to avoid sexual intercourse, even if antiviral treatment has already been started. Suppressive therapy with antiviral drugs significantly reduces the risk of transmission of genital herpes, but does not completely eliminate it. In these cases, therapy with Valtrex is recommended in combination with the use of protective agents during sexual intercourse. Use in ophthalmic HSV infections It is necessary to carefully monitor the clinical efficacy of the drug in this category of patients. Consideration should be given to intravenous antiviral therapy if the effectiveness of oral therapy is insufficient. Use in CMV infections. Data on the efficacy of valaciclovir in organ transplant recipients (~200) who are at increased risk for CMV infection (eg, CMV-positive donor/CMV-negative recipient or use of antithymocyte globulin induction therapy) indicate that valaciclovir is necessary use only in patients for whom the use of valganciclovir or ganciclovir is contraindicated for safety reasons. The use of high doses of valaciclovir for the prevention of CMV infections may lead to an increase in the frequency of adverse reactions, including disorders of the central nervous system, compared with the use of lower doses of the drug for other indications (see section "Precautions"). It is necessary to carefully monitor changes in renal function and adjust doses accordingly (see section "Method of application and dosage"). Interaction with other drugs Care must be taken when combining valaciclovir with nephrotoxic drugs, especially in patients with impaired renal function, regular monitoring of renal function is recommended. This provision applies to the co-administration of valaciclovir with aminoglycosides, platinum compounds, iodinated contrast agents, methotrexate, pentamidine, foscarnet, cyclosporine, tacrolimus. Aciclovir is excreted mainly unchanged in the urine by active secretion. After taking 1000 mg of valacyclovir, cimetidine and probenecid reduce the renal clearance of acyclovir and increase the AUC of acyclovir by approximately 25% and 45%, respectively, by blocking the tubular secretion of acyclovir. Cimetidine and probenecid, when co-administered with valacyclovir, increase the AUC of acyclovir by approximately 65%. Other drugs (eg, tenofovir) taken concomitantly that compete with or interfere with active tubular secretion may increase aciclovir concentrations through these mechanisms. In addition, valaciclovir may increase plasma concentrations of co-administered agents. In patients with a higher exposure to acyclovir while taking valaciclovir (for example, for the treatment of herpes zoster or the prevention of CMV), caution should be exercised in case of simultaneous use with drugs that inhibit active renal tubular secretion. An increase in the AUC of acyclovir and the inactive metabolite of the immunosuppressive drug mycophenolate mofetil has been noted with the simultaneous use of these drugs in patients after transplantation. No changes in peak concentrations or AUC were observed with the co-administration of valaciclovir and mycophenolate mofetil in healthy volunteers. There is limited clinical experience with this combination. Contraindications Valtrex is contraindicated in patients with hypersensitivity to valacyclovir, acyclovir or any of the excipients that make up the drug. Composition Active substance: valaciclovir hydrochloride 556 mg (equivalent to 500 mg valaciclovir). Excipients: microcrystalline cellulose, crospovidone, povidone K 90, magnesium stearate, anhydrous colloidal silicon dioxide, white dye concentrate YS-1-18043, carnauba wax. Tablet shell: hydroxypropyl methylcellulose, titanium dioxide (E171), polyethylene glycol 400, polysorbate 80. to whom. In addition, side effects such as nausea and vomiting may occur. Care should be taken to avoid accidental overdose. Many reports of overdose cases have concerned patients with impaired renal function and elderly patients who received repeated doses of valaciclovir in the absence of an appropriate dose reduction. Treatment: Patients should be closely monitored for signs of toxicity. Hemodialysis significantly enhances the removal of acyclovir from the blood and may be considered the treatment of choice in the management of patients with symptoms of Valtrex overdose. Side effects The most common adverse reactions observed with Valtrex for at least one indication in clinical trials were headache and nausea. Details of more serious adverse reactions such as thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, acute renal failure and neurological disorders are provided below. Adverse reactions are listed below in accordance with the classification by major systems and organs and by frequency of occurrence. Frequency rates used: Very common: ≥1 in 10 Common: ≥1 in 100 and <1 in 10 Uncommon: ≥1 in 1000 and <1 in 100 Rare: ≥1 in 10,000 and <1 in 1000 Very rare: <1 in 1000 10000. The frequency of occurrence of adverse reactions was determined on the basis of data from clinical studies in the case of establishing a causal relationship with the use of valaciclovir. For post-marketing adverse events that were not observed in clinical trials, the frequency category was determined based on the most conservative point estimation approach (the "rule of three"). For adverse reactions that were identified during post-marketing experience of use, and also observed in clinical studies, the frequency category was determined based on the frequency in the studies. The safety data in the clinical trial database is based on information from 5855 patients who received valaciclovir in clinical trials for various indications (treatment of herpes zoster, treatment/suppression of genital herpes and treatment of herpes labialis). Nervous system disorders Very common: headache. Gastrointestinal disorders Common: Nausea. Post-marketing data Blood and lymphatic system disorders Uncommon: leukopenia, thrombocytopenia. The development of leukopenia has been reported mainly in immunocompromised patients. Immune system disorders Rare: anaphylaxis. Mental disorders and disorders of the nervous system Often: dizziness. Uncommon: confusion, hallucinations, disturbances of consciousness, agitation, tremor. Rare: ataxia, dysarthria, psychotic symptoms, convulsions, encephalopathy, coma, delirium. Neurological disturbances, sometimes severe, may be associated with encephalopathy and include confusion, agitation, seizures, hallucinations, coma. These symptoms are generally reversible and usually occur in patients with impaired renal function or other predisposing conditions (see Precautions section). In organ transplant patients receiving high doses (8000 mg per day) of the drug Valtrex for the prevention of CMV infection, neurological reactions develop more often than when taking lower doses for other indications. Respiratory, thoracic and mediastinal disorders Uncommon: dyspnea. Gastrointestinal disorders Common: Vomiting, diarrhea. Uncommon: abdominal discomfort. Liver and biliary tract disorders Uncommon: reversible abnormal liver function tests (bilirubin, liver enzymes, etc.). Skin and subcutaneous tissue disorders Common: rash including photosensitivity, itching Uncommon: urticaria. Rare: angioedema. Renal and urinary tract disorders Uncommon: Renal pain, hematuria (often associated with other renal disorders) Rare: Renal dysfunction, acute renal failure (especially in elderly patients or in patients with impaired renal function receiving doses of the drug higher than recommended). Pain in the kidney area may be associated with impaired renal function. There have been reports of cases of precipitation of crystals of acyclovir in the lumen of the renal tubules. It is necessary to ensure adequate fluid intake during treatment (see section "Precautions"). Additional information on use in special groups of patients: in patients with severely impaired immunity, especially in patients with advanced HIV infection, who received high doses of valaciclovir (8000 mg daily) for a long period of time in clinical studies, there were cases of renal failure, microangiopathic hemolytic anemia and thrombocytopenia (sometimes in combination). Similar complications have been noted in patients with the same diseases, but not receiving valaciclovir. In case of adverse reactions, including those not listed in the instructions for use, you should consult a doctor. Storage conditionsStore at a temperature not exceeding 3. Buy Valtrex tablets p/o 500mg No. 10x1