Valganciclovir-Teva 450mg pills, 60pcs

Composition

1 tablet contains:

Active ingredient:  valganciclovir hydrochloride 496.30 mg (valganciclovir 450.00 mg);

excipients:  microcrystalline cellulose 70.00 mg; mannitol 86.23 mg; colloidal silicon dioxide 3.40 mg; crospovidone (type A) 10.05 mg; magnesium stearate 4.02 mg;

shell:  Opadry II 32 To 54870 pink: hypromellose-15 CP/NRMS 2910 (E 464) 10,720 mg; lactose monohydrate 6,700 mg; titanium dioxide (E 171) 6,218 mg; triacetin (E 1518) 2,948 mg; dye iron oxide red (E 172) 0,214 mg.

Pharmacological properties

Pharmacotherapeutic group: Antiviral Crestwood: J. 05. A. B. 14 Valganciclovir

J. 05. A. B Nucleosides and nucleotides

Pharmacodynamics :

Mechanism of action

An antiviral drug. Valganciclovir is an L-valyl ester (prodrug) of ganciclovir, which is rapidly converted to ganciclovir after oral use by intestinal and hepatic esterases. Ganciclovir is a synthetic analog of 2′ – deoxyguanosine, which inhibits the reproduction of herpes viruses in vitro and in vivo. Human viruses that are sensitive to ganciclovir include cytomegalovirus (CMV), Herpes simplex types 1 and 2, human herpes virus types 6,7 and 8 (HHV-6, HHV-7, HHV-8), Epstein-Barr virus, Varicella zoster virus and hepatitis B virus. In CMV-infected cells, under the action of viral protein kinase UL97, ganciclovir is initially phosphorylated to form ganciclovir monophosphate. Further phosphorylation occurs under the action of cellular kinases with the formation of ganciclovir triphosphate. which then undergoes slow intracellular metabolism. It was shown that this metabolism occurs in cells infected with CMV and Herpes simplex, and after the disappearance of ganciclovir from the extracellular fluid, the intracellular half-life of the drug is 18 hours and 6-24 hours, respectively. Since ganciclovir phosphorylation largely depends on the action of viral kinase, it occurs mainly in infected cells.

The virostatic activity of ganciclovir is due to the suppression of the synthesis of viral deoxyribonucleic acid (DNA) by:

1) competitive inhibition of deoxyguanosine triphosphate incorporation into DNA under the action of viral DNA polymerase;

2) incorporation of ganciclovir triphosphate into viral DNA, resulting in the cessation of elongation or very limited elongation of viral DNA. A typical inhibitory concentration that inhibits CMV replication by 50% (IC50), determined in vitro, ranges from 0.08 mmol/L (0.02 mcg / ml) to 0.14 mmol/L (3.5 mcg/ml).

The clinical antiviral effect of valganciclovir was shown to reduce CMV excretion from the body of patients with acquired immunodeficiency syndrome (AIDS) and newly diagnosed CMV retinitis from the initial indicator of 46% to 7% after 4 weeks of treatment with valganciclovir.

Efficiency

Treatment of CMV retinitis. The use of valganciclovir in induction therapy in patients with CMV retinitis has the same clinical efficacy compared to intravenous (iv) use of the recommended doses of ganciclovir. effective in the treatment of CMV retinitis. The area under the concentration-time curve (AUC) of ganciclovir was shown to correlate with the length of time before CMV retinitis progressed.

Prevention of CMV infection. Frequency of CMV disease (CMV syndrome + invasive tissue infection) during the first 6 months after heart, liver, and kidney transplantation in patients at high risk of developing CMV infection (CMV-positive donor (D+)/CMV-negative recipient (R -) (D+/R -)) It was 12.1% in patients receiving valganciclovir at a dose of 900 mg / day and 15.2% in patients taking oral ganciclovir at a dose of 1 g 3 times a day from the 10th to the 100th day after transplantation. Most of the cases occurred after the withdrawal of preventive therapy (after the 100th day of the post-transplant period). At the same time, cases of CMV infection in the valganciclovir treatment group appeared later than in the ganciclovir treatment group. The incidence of acute rejection in the first 6 months was 29.7% in patients treated with valgancyclovir and 36% in patients treated with ganciclovir. The 12-month transplant survival rate was 98.2% in patients treated with valgancyclovir before day 100 and 98.1% in patients treated with valgancyclovir before day 200. The incidence of acute graft rejection confirmed by biopsy in the first 12 months was 17.2% in patients treated with valgancyclovir before day 100, and 11% in patients treated with valgancyclovir before day 200.

Viral resistance. If valganciclovir is taken for a long time, a virus resistant to ganciclovir may appear, which may be due to the selection of mutations either in the viral kinase (UL97) gene responsible for ganciclovir monophosphorylation, or in the viral DNA polymerase (UL54) gene. A virus with only the UL97 gene mutation is only resistant to ganciclovir, while a virus with mutations in the UL54 gene may have cross-resistance to other antiviral drugs with a similar mechanism of action, and vice versa.

Treatment of CMV retinitis. Genotyping of CMV in polymorphonuclear leukocytes showed that after 3,6,12, and 18 months of valganciclovir treatment, UL97 mutations were detected in 2.2%,6.5%,12.8%, and 15.3% of leukocytes, respectively.

Prevention of CMV infection in patients after solid organ transplantation.

Genotyping of CMV in polymorphonuclear leukocytes showed:

1) the absence of mutations causing resistance to ganciclovir in samples obtained on day 100 (end of valganciclovir prophylaxis) in patients taking valganciclovir, and the presence of mutations in samples obtained in patients taking ganciclovir orally. 2) the absence of mutations that cause resistance in samples obtained from patients taking valganciclovir with suspected CMV infection 6 months after transplantation, and the presence of mutations in patients taking ganciclovir orally.

Preclinical safety data.

Valganciclovir and ganciclovir had mutagenic effects in murine lymphoma cells and clastogenic effects in mammalian cells. These results are consistent with the positive results of the mouse carcinogenicity study of ganciclovir. Like ganciclovir, valganciclovir is a potential carcinogen. Reproductive toxicity studies with valganciclovir were not repeated due to the rapid and complete conversion of the drug to ganciclovir. The same warning about possible reproductive toxicity applies to both drugs. In animals, ganciclovir disrupts fertility and has a teratogenic effect. Based on animal experiments in which systemic exposure to ganciclovir at concentrations below therapeutic levels caused aspermia, it is highly likely that ganciclovir and valganciclovir may inhibit spermatogenesis in humans. Data obtained in an ex vivo human placenta model indicate that ganciclovir passes through the placental barrier, most likely by simple transfer. In the concentration range from 1 to 10 mg/ml, the drug was unsaturated and passed through the placenta by passive diffusion. Pharmacokinetics:

The pharmacokinetic characteristics of valganciclovir were studied in HIV-and CMV-seropositive patients, in patients with AIDS and CMV retinitis, as well as after solid organ transplantation.

Bioavailability and renal function determine the exposure of ganciclovir after taking valganciclovir. The bioavailability of ganciclovir was similar in all patients treated with valganciclovir. The systemic exposure of ganciclovir to heart, kidney, and liver transplant recipients was similar to that after oral valganciclovir in accordance with the dosage regimen depending on renal function. Suction. Valganciclovir is a prodrug of ganciclovir. It is well absorbed from the gastrointestinal tract, and rapidly converts to ganciclovir in the intestinal wall and liver. The absolute bioavailability of ganciclovir after taking valganciclovir is about 60%. Systemic exposure to valganciclovir is low and short-lived. AUC24 and maximum plasma concentrations (Cmax) are approximately 1% and 3% of those of ganciclovir, respectively. The proportional dependence of the AUC of ganciclovir on the dose after taking valganciclovir in doses from 450 to 2625 mg is shown only for the case of taking valganciclovir after a meal. If valganciclovir is used during a meal at the recommended dose of 900 mg. increases as the average AUC24 (approximately 30%). so is the average Cmax (by approximately 14%) of ganciclovir. Therefore, valganciclovir is recommended to be taken with a meal. Distribution. Due to the rapid metabolism of valganciclovir to ganciclovir. protein binding of valganciclovir was not determined. The binding of ganciclovir to plasma proteins at concentrations from 0.5 to 51 mcg/ml is 1-2%. The steady-state volume of distribution of ganciclovir after intravenous use was 0.680±0.161 l / kg. Metabolism. Valganciclovir is rapidly hydrolyzed to form ganciclovir; no other metabolites were found. After a single oral dose of 1000 mg of radiolabeled ganciclovir, the radioactivity of none of the metabolites in feces or urine was no more than 1-2%.

Output. The main route of elimination of valganciclovir.like ganciclovir. there is glomerular filtration and active tubular secretion. Renal clearance accounts for 81.5±22% of the systemic clearance of ganciclovir.

Pharmacokinetics in special clinical cases

Patients with renal insufficiency

Deterioration of renal function led to a decrease in the clearance of ganciclovir. formed from valganciclovir, with a corresponding increase in T 1/2 in the terminal phase. Therefore, dose adjustment is required in patients with impaired renal function.

Patients with hepatic insufficiency

The pharmacokinetics of valganciclovir were studied in patients with a stable functioning liver transplant. Absolute bioavailability of ganciclovir. The dose of valganciclovir (with a single oral dose of 900 mg after a meal) was approximately 60%, which coincides with the indicator in other patients. The AUC0-24 of ganciclovir was comparable to that after intravenous use of ganciclovir at a dose of 5 mg / kg to patients undergoing liver transplantation.

Indications

Treatment of CMV retinitis in AIDS patients;

Prevention of CMV infection in patients after solid organ transplantation in adults and children over 16 years of age at risk.

Use during pregnancy and lactation

Reproductive toxicity studies with valganciclovir were not repeated due to the rapid and complete conversion of valganciclovir to ganciclovir. Ganciclovir disrupts fertility and has a teratogenic effect in animals.

During treatment with Valganciclovir-Teva, women of reproductive age should be advised to use effective methods of contraception. Men are recommended to use a barrier method of contraception during treatment with Valganciclovir-Teva and at least 90 days after its end.

The safety of valganciclovir during pregnancy in humans has not been established. During pregnancy, the use of Valganciclovir-Teva should be avoided, except in cases where the expected benefit to the mother exceeds the possible risk to the fetus.

Peri-and postnatal development with valganciclovir and ganciclovir has not been studied, but the possibility of ganciclovir excretion in breast milk and the development of serious adverse reactions in an children cannot be excluded. Therefore, the decision to discontinue Valganciclovir-Teva or stop breastfeeding should be made based on an assessment of the potential effect of the treatment on the nursing mother and the risk to the infant.

Contraindications

Hypersensitivity to valganciclovir, ganciclovir or other components of the drug. Due to the similar chemical structure of acyclovir, valacyclovir and valganciclovir, cross-sensitivity reactions are possible;

Absolute neutrophil count (APN) less than 500 / µl; platelet count less than 25,000/µl; hemoglobin concentration less than 80 g / l;

Creatinine clearance less than 10 ml / min.

Children under 16 years of age (prevention of CMV infection after solid organ transplantation in adults and children over 16 years of age at risk);

– children under 18 years of age (treatment of CMV retinitis in adult AIDS patients).

With caution:

Elderly patients (safety and efficacy have not been established).

Side effects

Valganciclovir is a prodrug of ganciclovir. Valganciclovir is rapidly converted to ganciclovir after oral use, so all known adverse events (AES) reported with ganciclovir are expected with valganciclovir.

In the treatment of CMV retinitis in patients with AIDS

The safety profiles of valganciclovir and ganciclovir when administered intravenously for 28 days were the same. The most common AES were diarrhea, neutropenia, and fever. Oral candidiasis has been reported more frequently in patients taking valganciclovir orally. headache and weakness, patients with intravenous ganciclovir were more likely to experience nausea and AES at the injection site (phlebitis and thrombophlebitis) (see Table 1).

Table 1. Proportion of patients (% ) with individual AES in the treatment of CMV retinitis

Table 2 shows the most frequent AES (regardless of their severity and association with valganciclovir) with a frequency of at least 5% obtained during treatment with valganciclovir or in patients with CMV retinitis. or in patients after solid organ transplantation.

Neutropenia (21%), diarrhea (14%), nausea (9%), and anemia (14%) were the most common AES, regardless of severity, but associated with valganciclovir (long-term, probable, or possible association) in patients with CMV retinitis.

In the prevention of CMV retinitis in patients after organ transplantation

Table 2 shows adverse events (up to 28 days after completion of the study) regardless of their severity and their association with the drug, with a frequency of ≥5%, obtained in clinical studies in patients after solid organ transplantation who received valganciclovir or ganciclovir orally, starting taking the drugs within 10 days after transplantation and continuing to take them until the 100th day of the post-transplant period.

The most common adverse reactions, regardless of severity, but, according to researchers, associated with taking the drug (long-term, probable or possible relationship) in patients after solid organ transplantation who received treatment before the 100th day of the post-transplant period: leukopenia, diarrhea, nausea, neutropenia; in patients who underwent kidney transplantation and received treatment before the 200th day of the post-transplant period: leukopenia, neutropenia, anemia and diarrhea.

Table 2. Proportion of patients (% ) with AE that occurred in at least 5% of patients with CMV retinitis or after organ transplantation during valganciclovir and ganciclovir therapy

The following are serious adverse events associated with valganciclovir, occurring with a frequency of less than 5%, not mentioned above.

Blood and lymphatic system disorders: pancytopenia, bone marrow suppression, aplastic anemia, febrile neutropenia, potentially life-threatening bleeding associated with the development of thrombocytopenia.

From the urinary system: reduced QC.

Nervous system disorders: convulsions, psychotic disorders, hallucinations, confusion, agitation.

Other services: hypersensitivity reactions to valganciclovir.

Severe neutropenia (absolute neutrophil count less than 500 in 1 µl) is more common in patients with CMV retinitis (16%) than in patients receiving valganciclovir (5%) or oral ganciclovir (3%) after organ transplantation before the 100th day of the post-transplant period or in patients receiving valganciclovir (10%) before the 200th day of the post-transplant period. Patients receiving both valganciclovir and ganciclovir orally after organ transplantation before day 100 or day 200 of the post-transplant period showed a more significant increase in serum creatinine concentrations compared to patients with CMV retinitis. Impaired renal function is characteristic of patients who have undergone organ transplantation. The overall safety profile of valganciclovir does not change with an increase in the period of prophylactic use to 200 days in patients after a kidney transplant at risk. In patients receiving valganciclovir before day 200 for the post-transplant period, compared with patients receiving valganciclovir before day 100 for the post-transplant period, there is a slight increase in the incidence of leukopenia.

The incidence of neutropenia, anemia, and thrombocytopenia is similar in patients treated before day 100 and day 200 of the post-transplant period.

Table 3. Laboratory parameters when using valganciclovir

Experience with ganciclovir

Since valganciclovir is rapidly converted to ganciclovir, the AES described in ganciclovir treatment and not mentioned above are listed below.

From the digestive system: dryness of the oral mucosa, cholangitis, dysphagia, belching, esophagitis, fecal incontinence, flatulence, gastritis, gastrointestinal disorders, gastrointestinal bleeding, ulcerative stomatitis, pancreatitis, glossitis, hepatitis, jaundice.

From the body as a whole: asthenia, bacterial, fungal and viral infections, malaise, mucositis, tremors, sepsis.

Skin and subcutaneous tissue disorders: alopecia, photosensitivity reactions, dry skin, sweating, urticaria.

Nervous system disorders: sleep disorders, amnesia, anxiety, ataxia, coma, emotional disorders, hyperkinesis, hypertonus, decreased libido, myoclonic twitching, nervousness, drowsiness, intellectual impairment.

From the musculoskeletal system: bone and muscle pain, myasthenic syndrome.

From the genitourinary system: hematuria, impotence, frequent urination.

Laboratory parameters: increased activity of alkaline phosphatase, creatinine phosphokinase, lactate dehydrogenase in blood plasma, decreased blood glucose concentration, hypoproteinemia.

From the side of the senses: amblyopia, blindness, ear pain, eye hemorrhage, eyeball pain, deafness, glaucoma, taste disorders, tinnitus, visual impairment, non-systemic dizziness, changes in the vitreous body.

From the hematopoietic system: eosinophilia, leukocytosis, lymphadenopathy, splenomegaly, bleeding.

From the cardiovascular system: arrhythmias (including ventricular ones), deep vein thrombophlebitis, migraines, phlebitis, tachycardia, vasodilation.

Respiratory system disorders: congestion in the paranasal sinuses.

From the endocrine system: diabetes mellitus.

Children

Prevention of CMV infection in patients after organ transplantation

Table 4 shows the adverse events that occurred up to 28 days after the end of the study regardless of their severity and in connection with taking the drug.

The table includes adverse events with a frequency of ≥10% reported in clinical studies in children aged 3 weeks to 16 years after solid organ transplantation who started valganciclovir within 10 days after transplantation and continued treatment until day 100 of the post-transplant period, as well as in children after kidney transplantation who started valganciclovir within 10 days after transplantation and continued treatment until day 200 of the post-transplant period.

The overall safety profile of valganciclovir in children does not differ from the safety profile of the drug in adults. Some adverse events were observed in children with a higher frequency than in adults, such as upper respiratory tract infections, fever, abdominal pain and dysuria, which may reflect the characteristics of the child population. In the pediatric population, there was a slight increase in the incidence of neutropenia, but this did not lead to an increase in the frequency of infections.

In children who have undergone kidney transplantation, an increase in the period of preventive use to 200 days does not lead to an increase in the frequency of adverse events.

Table 4. Adverse events that occurred with a frequency of ≥ 10% in children after solid organ transplantation.

Severe neutropenia was more frequently observed in children who underwent kidney transplantation and received valganciclovir before the 200th day of the post-transplant period, compared with children who received valganciclovir before the 100th day of the post-transplant period, and compared with adults who underwent kidney transplantation and received valganciclovir before the 100th and 200th days of the post-transplant period.

Congenital CMV infection

Limited data available indicate that the safety profile of valganciclovir or ganciclovir under 6 months of age for the treatment of congenital CMV infection in newborns aged 2 to 31 days does not differ from that in adults. Grade 3 and 4 neutropenia were most frequently reported with ganciclovir (38%). In only one case, antiviral therapy was discontinued due to the development of neutropenia. in all other cases, neutropenia was corrected without discontinuation of therapy. All newborns showed an increase in indicators that characterize growth and development (height, body weight, average head circumference). When using valganciclovir, the most common adverse events were neutropenia. anemia, impaired liver function and diarrhea (it should be noted that these adverse events occurred in patients who did not receive the drug, and with a higher frequency than in patients who received the drug). The only serious treatment-related adverse events were neutropenia and anemia (also more commonly seen in patients who did not receive the drug). There were no statistically or clinically significant differences between valganciclovir-treated and non-valganciclovir-treated patients in terms of height and development (height, body weight, average head circumference).

Table 5. Changes in laboratory parameters when using valganciclovir in children

Experience of post-marketing drug use

The AES described in spontaneous reports during post-marketing use of ganciclovir are listed below. not mentioned in any of the above sections, for which a causal relationship with valganciclovir cannot be excluded. Since valganciclovir is rapidly and largely converted to ganciclovir, these side effects can also develop during treatment with valganciclovir: anaphylaxis, decreased fertility in men.

The AES reported with post-marketing use of valganciclovir are similar to those observed in clinical trials of valganciclovir and ganciclovir.

Interaction

No interaction of valganciclovir with valacyclovir, didanosine, nelfinavir, cyclosporine, omeprazole, and mycophenolate mofetil was detected in an in situ model of intestinal permeability in rats.

Valganciclovir is converted to ganciclovir, so interactions characteristic of ganciclovir can also be expected when using valganciclovir.

The binding of ganciclovir to plasma proteins is only 1-2%, so reactions associated with protein binding substitution should not be expected.

Seizures have been reported in patients receiving concomitant treatment with ganciclovir and imipenem/cilastatin. Concomitant use of these drugs should be avoided unless the expected benefit outweighs the possible risk. Concomitant oral use of probenecid may result in an approximately 20% decrease in the renal clearance of ganciclovir and an increase in the duration of its action (40%). This is explained by the mechanism of interaction-competition for tubular renal excretion. Patients taking probenecid and valganciclovir concomitantly should be monitored for ganciclovir toxicity. When used concomitantly with ganciclovir for oral use, the AUC of zidovudine may increase slightly, but statistically significantly (17%); in addition, there is a statistically insignificant trend towards a decrease in the concentration of ganciclovir. Since both zidovudine and ganciclovir can cause neutropenia and anemia, some patients may not be able to tolerate the simultaneous use of these drugs in full doses.

Plasma concentrations of didanosine were found to persistently increase with simultaneous intravenous and oral use of ganciclovir. When taking ganciclovir orally at a dose of 3 g and 6 g / day. The AUC of didanosine increased by 84-124%, and with intravenous use of ganciclovir at doses of 5-10 mg / kg / day. The AUC of didanosine increased by 38-67%. This increase cannot be explained by competition for renal tubular excretion, since the percentage of didanosine excretion increased. The reason for this increase may be either increased bioavailability or inhibition of metabolism. There was no clinically significant effect on ganciclovir concentrations. However, given the increased plasma concentrations of didanosine in the presence of ganciclovir, patients should be carefully monitored for symptoms of toxic effects of didanosine.

Taking into account the results of the study on a single use of the recommended dose of intravenous ganciclovir and oral mycophenolate mofetil, as well as the known effect of impaired renal function on the pharmacokinetics of ganciclovir and mycophenolate mofetil, it can be expected that the simultaneous use of these drugs competing in the process of tubular secretion will lead to an increase in the concentration of ganciclovir and mycophenolic acid phenolic glucuronide. No significant changes in the pharmacokinetics of mycophenolic acid are expected, and no dose adjustment of mycophenolate mofetil is required. In patients with impaired renal function who are simultaneously receiving valganganciclovir and mycophenolate mofetil, the recommendations for dose adjustment of ganciclovir should be followed and careful monitoring should be carried out.

Zalcitabine increases the AUC0-8 of oral ganciclovir by 13%. There were no statistically significant changes in other pharmacokinetic parameters. Clinically significant changes in the pharmacokinetics of zalcitabine with concomitant oral use of ganciclovir were also absent, despite a slight increase in the elimination rate constant.

No statistically significant pharmacokinetic interaction was observed with concomitant oral use of stavudine and ganciclovir.

Trimethoprim statistically significantly (by 16.3%) reduces the renal clearance of ganciclovir taken orally, which is accompanied by a statistically significant decrease in the rate of terminal elimination and a corresponding increase in Ts by 15%. However, the clinical significance of these changes is unlikely, since AUC0-8 and Cmax do not change. The only statistically significant change in the pharmacokinetic parameters of trimethoprim with simultaneous use of ganciclovir was an increase in Cmin. However, this is unlikely to be clinically relevant, so no dose adjustment is required.

When comparing cyclosporine concentrations before taking the next dose, there was no evidence that ganciclovir changes the pharmacokinetics of cyclosporine. However, after starting ganciclovir, there was a slight increase in the maximum serum creatinine concentration.

The use of ganciclovir concomitantly with other drugs that have a myelosuppressive effect or impair renal function (for example, dapsone, pentamidine, flucytosine, vincristine, vinblastine, adriamycin, amphotericin B, nucleoside analogues and hydroxyurea) may increase their toxic effect. Therefore, these drugs can be used simultaneously with ganciclovir only if the potential benefit outweighs the possible risk.

Other possible drug interactions: since the main route of elimination of ganciclovir is glomerular filtration and active tubular secretion, the use of valganciclovir simultaneously with antiretroviral drugs that are also eliminated by active tubular secretion(for example, nucleose (t)id reverse transcriptase inhibitors) may affect the concentration of valganciclovir and/or co-administered drugs. Concomitant use of ganciclovir with other drugs that have a myelosuppressive or nephrotoxic effect (for example, dapsone, pentamidine, flucytosine, vincristine, vinblastine, adriamycin, amphotericin B, nucleoside analogues, hydroxycarbamide, and pegylated interferons/ribavirin) may increase their toxic effects. Therefore, these drugs can be used simultaneously with valganciclovir only if the expected benefit of the treatment exceeds the possible risk.

How to take it, course of use and dosage

To avoid overdose, it is necessary to strictly follow the dosage recommendations.

Standard dosage regimen

Valganciclovir-Teva should be taken orally during meals. Valganciclovir-Teva is rapidly and largely metabolized to ganciclovir. The bioavailability of ganciclovir when taking Valganciclovir-Teva is 10 times higher than when taking ganciclovir orally. Therefore, it is necessary to strictly adhere to the dosage regimen of Valganciclovir-Teva described below.

CMV retinitis therapy

Adults

Induction therapy of CMV retinitis

In patients with active CMV retinitis, the recommended dose of Valganciclovir-Teva is 900 mg (2 tablets of 450 mg) 2 times a day for 21 days. Long-term induction therapy increases the risk of myelotoxicity.

CMV-retinitis maintenance therapy

After a course of induction therapy or in patients with inactive CMV retinitis, the recommended dose is 900 mg (2 tablets of 450 mg) once a day. If the course of retinitis worsens, the course of induction therapy can be repeated.

Prevention of CMV infection after solid organ transplantation

Adults

Patients who have undergone kidney transplantation, therapy begins within the first 10 days after surgery at a dose of 900 mg (2 tablets of 450 mg) once a day. Continue therapy on the 200th day of the posttransplantation period.

Patients who have undergone transplantation of other solid organs, therapy begins within the first 10 days after surgery at a dose of 900 mg (2 tablets of 450 mg) once a day. Continue therapy on the 100th day of the posttransplantation period.

Special dosage instructions

In patients with renal insufficiency, serum creatinine or creatinine clearance should be carefully monitored. Dose adjustment is carried out depending on the creatinine clearance, as shown in the table below.

CC is calculated depending on the concentration of creatinine in the blood serum using the following formula:

for men = (140 – age) x body weight (kg)/72 x (0.011 x serum creatinine concentration (mmol / L);

for women = 0.85 x indicator for men.

Patients on hemodialysis (creatinine clearance less than 10 ml / min) it is not recommended to use valganciclovir.

In patients with severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow suppression, aplastic anemia, treatment should not be initiated if the APN is less than 500/µl or the platelet count is less than 25,000/µl, or if the hemoglobin concentration is below 80 g/l.

Patients with severe leukopenia, neutropenia, anemia and/or thrombocytopenia should be prescribed hematopoietic growth factors and / or discontinue the drug.

Caution should be exercised in elderly patients, as efficacy and safety have not been established.

Children’s age

CMV retinitis therapy

It is not recommended to use Valganciclovir-Teva tablets in children under 18 years of age for the treatment of CMV retinitis, since the effectiveness and safety of Valganciclovir-Teva in this age group has not been established.

Prevention of CMV infection after solid organ transplantation

The dosage regimen for children aged 16 to 18 years does not differ from the dosage regimen for adults. Valganciclovir-Teva tablets are not recommended for use in children and adolescents under 16 years of age in order to prevent CMV infection after solid organ transplantation, since the effectiveness and safety of Valganciclovir-Teva in this age group has not been established.

Overdose

In one adult patient, the use of the drug for several days at doses not less than 10 times higher than recommended for him, taking into account kidney damage (decreased creatinine clearance), developed bone marrow suppression (medullary aplasia) with a fatal outcome.

It is possible that an overdose of valganciclovir may lead to nephrotoxicity. To reduce the concentration of valganciclovir in the blood plasma in patients with overdose, it is possible by hemodialysis and hydration.

Overdose of ganciclovir with intravenous use

During clinical studies and post-marketing use of the drug, cases of overdose of intravenously administered ganciclovir were described. Some of them were not accompanied by AES. In the majority of patients had one or more of the following AES:

hematological toxicity (pancytopenia, inhibition of the function of the bone marrow, medullary aplasia, leukopenia, neutropenia, granulocytopenia);

– hepatotoxicity (hepatitis, abnormal liver function);

– nephrotoxicity (increased hematuria in patients with existing kidney disease, acute renal failure, increased creatinine concentration);

– gastrointestinal toxicity (abdominal pain, diarrhea, vomiting);

– neurotoxicity (generalized tremor, convulsions).

Special instructions

Experimental studies on animals revealed mutagenic, teratogenic, spermatocidal and carcinogenic effects of ganciclovir. The drug Valganciclovir-Teva should be considered a potential teratogen and carcinogen for humans, the use of which can cause congenital malformations and cancer. In addition, it is likely that Valganciclovir-Teva may temporarily or permanently inhibit spermatogenesis.

Cases of severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow suppression, and aplastic anemia have been reported in patients receiving Valganciclovir-Teva (and ganciclovir). Treatment should not be initiated if the APN is less than 500 / µl, or the platelet count is less than 25,000/µl, or if the hemoglobin concentration is below 80 g/l.

During treatment, it is recommended to regularly monitor the detailed formula of blood and platelets. Patients with severe leukopenia, neutropenia, anemia, and/or thrombocytopenia are advised to use hematopoietic growth factors and / or discontinue the drug.

Long-term induction therapy with Valganciclovir-Teva increases the risk of myelotoxicity.

Patients with concomitant use of ganciclovir and imipenem/cilastatin may develop seizures. Concomitant use of valganciclovir and imipenem / cilastatin should be avoided if the expected benefit does not exceed the possible risk.

Since both zidovudine and ganciclovir can cause neutropenia and anemia, some patients may experience intolerance when valganciclovir and zidovudine are co-administered at full doses.

Due to the possible increase in plasma concentrations of didanosine in the presence of ganciclovir, patients should be carefully monitored for symptoms of toxic effects of didanosine.

The use of Valganciclovir-Teva concomitantly with other drugs that have a myelosuppressive or nephrotoxic effect may increase their toxic effect.

It is not recommended to use Valganciclovir-Teva in children. Pharmacokinetic characteristics, safety and efficacy of the drug in this population have not been established.

The bioavailability of ganciclovir from Valganciclovir-Teva is 10 times higher than that of ganciclovir capsules. Ganciclovir should not be substituted for Valganciclovir-Teva in a ratio of 1: 1. Patients who are transferred from ganciclovir capsules should be informed of the risk of overdose if they take more Valganciclovir-Teva tablets than recommended.

In patients with renal insufficiency, dose adjustment is required to take into account the value of creatinine clearance.

Rules for handling the drug

Tablets should not be broken or crushed. Since Valganciclovir-Teva is potentially teratogenic and carcinogenic to humans, care should be taken if the tablet breaks. Avoid direct contact of the broken or crushed tablet with the skin and mucous membranes. In cases of such contact, it is necessary to thoroughly wash this place with soap and water, in case of contact with the eyes, they should be thoroughly washed with water.

The release of medicinal products into the environment should be kept to a minimum. Do not dispose of the product using waste water or together with household waste. If possible, it is necessary to use special systems for disposing of medicines.

Influence on the ability to drive vehicles and fur. :

When treated with Valganciclovir-Teva and/or ganciclovir, seizures, sedation, dizziness, ataxia and/or confusion may occur, which may adversely affect activities that require increased concentration of attention, including driving vehicles and working with machines and mechanisms. In this regard, during treatment with Valganciclovir-Teva, care should be taken when driving vehicles and working with machines and mechanisms. If the described adverse events occur, you should refrain from performing these types of activities.

Storage conditions

At a temperature not exceeding 25°C.

Keep out of reach of children.

Shelf

life is 2 years.

Do not use after the expiration date.

Active ingredient

Valganciclovir

Conditions of release from pharmacies

By prescription

Dosage form

Tablets