Valcyte tablets 60 pcs

FarmGruppa: antiviral agent
.
Pharmacological action: Valganciclovir represents the L-valyl ester (prodrug) of ganciclovir, after ingestion rapidly converted to ganciclovir by intestinal and hepatic esterases.
Ganciclovir – a synthetic analogue of 2′-deoxyguanosine that inhibits replication of herpes group viruses in vitro and in vivo. For human viruses, sensitive to ganciclovir, include cytomegalovirus (CMV), herpes simplex viruses 1 and 2, 6 types of human herpes virus 7 and 8, Epstein-Barr virus, varicella zoster virus and hepatitis B virus in CMV-infected cells under action of viral UL97 protein kinase ganciclovir first phosphorylated to form gantsiklovirmonofosfata. Further phosphorylation occurs by cellular kinases to form gantsiklovirtrifosfata which is then subjected to slow intracellular metabolism. After the disappearance of ganciclovir from the extracellular fluid intracellular half-life period gantsiklovirtrifosfata in cells infected with CMV at 18 hours; in cells infected with the herpes simplex virus – 6-24 hours. Since the phosphorylation of ganciclovir is more dependent on the action of viral kinases, it occurs primarily in the infected cells.
Virostatic activity ganciclovir caused inhibition of viral DNA synthesis through the following mechanisms: (1) competitive inhibition dezoksiguanozintrifosfata incorporation into DNA by the action of the viral DNA polymerase; (2) gantsiklovirtrifosfata incorporation into viral DNA, which leads to the cessation of the elongation or very limited elongation viral DNA.
According to studies in vitro, a typical inhibitory concentration which inhibits CMV replication by 50% (IC50), is in the range of 0.08 mol (0.02 mg / ml) to 14 mol (3.5 ug / ml).
Clinical Valtsit® antiviral effect of the drug was proved decrease CMV isolation from an organism of patients with acquired immunodeficiency syndrome (AIDS) and newly diagnosed CMV retinitis with baseline 46% (32/69) 7% (4/55) after 4 weeks of treatment Valtsit® .
Efficiency
Treatment of CMV retinitis
Clinical studies have been conducted in patients with AIDS and CMV retinitis. Valtsit® drug showed the same clinical efficacy in the induction treatment of CMV retinitis in comparison with intravenous ganciclovir.
Application Valtsit® drug allows to obtain the same systemic exposure of ganciclovir, as when using the recommended dose of intravenous ganciclovir effective in the treatment of CMV retinitis. It is shown that the area under the curve “concentration-time» (AUC) of ganciclovir is correlated with the interval time to progression of CMV retinitis. Prevention of CMV disease Incidence of disease CMV (CMV syndrome + invasive tissue infection) during the first 6 months after transplantation of the heart, liver, kidneys in patients with high risk of CMV infection (D + / R-) was 12.1% in patients treated with Valcyte ® (900 mg daily), and 15.2% in the group of patients treated with ganciclovir administration (1000 mg 3 times a day), from 10 to 100 days after transplantation. Most of the cases occurred in the period after the abolition of preventive therapy (after the 100th day post-transplant period). The cases of CMV disease in valganciclovir treatment group appeared later than in treatment with ganciclovir group. The frequency of acute graft rejection during the first 6 months was 29.7% in patients treated with valganciclovir, and 36% in patients treated with ganciclovir. Increasing the duration of administration of 900 mg of the drug Valtsit® to 200 days after transplant of kidneys in patients with high risk of CMV infection (D + / R-) was accompanied by more effectively prevent CMV infection in the first 12 months after transplantation as compared with taking 900 mg of the drug Valtsit® up to 100 days after transplantation.
Frequency graft survival at 12 months was 98.1% in patients treated with the drug Valtsit® to 100-th day, and 98.2% in the group of patients receiving clinical antiviral effect of the drug was proved Valtsit® decrease CMV isolation from an organism of patients with acquired immunodeficiency syndrome (AIDS ) and newly diagnosed CMV retinitis with baseline 46% (32/69) 7% (4/55) after 4 weeks of treatment Valtsit®.
Efficiency
Treatment of CMV retinitis
Clinical studies have been conducted in patients with AIDS and CMV retinitis. Valtsit® drug showed the same clinical efficacy in the induction treatment of CMV retinitis in comparison with intravenous ganciclovir.
Application Valtsit® drug allows to obtain the same systemic exposure of ganciclovir, as when using the recommended dose of intravenous ganciclovir effective in the treatment of CMV retinitis. It is shown that the area under the curve “concentration-time» (AUC) of ganciclovir is correlated with the interval time to progression of CMV retinitis. Prevention of CMV disease Incidence of disease CMV (CMV syndrome + invasive tissue infection) during the first 6 months after transplantation of the heart, liver, kidneys in patients with high risk of CMV infection (D + / R-) was 12.1% in patients treated with Valcyte ® (900 mg daily), and 15.2% in the group of patients treated with ganciclovir administration (1000 mg 3 times a day), from 10 to 100 days after transplantation. Most of the cases occurred in the period after the abolition of preventive therapy (after the 100th day post-transplant period). The cases of CMV disease in valganciclovir treatment group appeared later than in treatment with ganciclovir group. The frequency of acute graft rejection during the first 6 months was 29.7% in patients treated with valganciclovir, and 36% in patients treated with ganciclovir. Increasing the duration of administration of 900 mg of the drug Valtsit® to 200 days after transplant of kidneys in patients with high risk of CMV infection (D + / R-) was accompanied by more effectively prevent CMV infection in the first 12 months after transplantation as compared with taking 900 mg of the drug Valtsit® up to 100 days after transplantation.
Frequency graft survival at 12 months was 98.1% in patients treated with the drug Valtsit® to 100-th day, and 98.2% in the group of patients receiving the drug to Valtsit® 200th day. The frequency of acute rejection confirmed by biopsy in the first 12 months was 17.2% in patients treated with valganciclovir 100 th day, and 11.0% in patients treated with valganciclovir 200 th day.

viral resistance
Chronic administration of valganciclovir virus can appear resistant to ganciclovir. This may be due to either mutation breeding viral kinase gene (UL97), responsible for the monophosphorylation of ganciclovir or a viral polymerase gene (UL54). The virus having only the mutation gene UL97, only resistant to ganciclovir, whereas virus with mutations in UL54 gene may have cross-resistance to other antiviral drugs with the same mechanism of action, and vice versa. Treatment of CMV retinitis Genotyping CMV in polymorphonuclear leukocytes showed that after 3, 6, 12 and 18 months of treatment valganciclovir respectively 2.2%, 6.5%, 12.8% and 15.3% are detected leukocytes UL97 mutation. Prevention of CMV disease in transplant patients Genotyping of CMV in polymorphonuclear leukocytes showed:
1) the absence of mutations causing resistance to ganciclovir, in samples obtained at the 100th day (end prophylactic valganciclovir) in patients from the group valganciclovir, and mutations in obtained from patient samples treated with ganciclovir orally (1.9%) < br>
2) absence of the mutations causing resistance in samples obtained from patients randomized to valganciclovir group with suspected CMV infection within 6 months after transplantation, and the presence of mutations in patients treated with ganciclovir orally in 6.9%.
Preclinical safety data
The results of carcinogenicity studies of valganciclovir in mice correspond to the positive results of the same studies ganciclovir. As with ganciclovir, valganciclovir is a potential carcinogen. Valganciclovir and ganciclovir mutagenic effect in lymphoma cells in mice and clastogenic effect in mammalian cells. Given the rapid and complete conversion of the drug ganciclovir, additional reproductive toxicity studies have not been conducted with valganciclovir. For both drugs include the same warning about a possible reproductive toxicity (see. “Special Instructions” section). In animals, ganciclovir violates fertility and has a teratogenic effect. In view of the experiments on animals in which ganciclovir systemic exposure at concentrations below the therapeutic causing spermatoschesis very likely that ganciclovir and valganciclovir may suppress sperm production in humans. The data obtained in a model using ex vivo human placenta suggest that ganciclovir crosses the placenta, probably by simple transfer. In the concentration range from 1 to 10 mg / ml of the drug across the placenta transition bore saturable nature and implemented by passive diffusion.
Pharmacokinetics: The pharmacokinetic characteristics of valganciclovir have been studied in HIV- and CMV-seropositive patients, patients with AIDS and CMV retinitis and after organ transplantation. Parameters determining the exposure ganciclovir valganciclovir are bioavailability, and renal function. The bioavailability of ganciclovir was similar in all patients receiving valganciclovir. Systemic exposure to ganciclovir recipients of heart transplant, a kidney, the liver was similar to that after oral administration of valganciclovir according to the dosing schedule depending on renal function.
suction
Valganciclovir is a prodrug of ganciclovir, it is well absorbed in the gastrointestinal tract, in the gut wall and the liver is rapidly metabolized to produce ganciclovir. The absolute bioavailability of ganciclovir valganciclovir is about 60%. Systemic exposure of valganciclovir is low and of short duration. The area under the curve “concentration-time» (AUC24) and maximum concentration (Cmax) constitute about 1% and 3% of those of ganciclovir, respectively.
Ganciclovir AUC proportional dependence of the dose after valganciclovir in doses ranging from 450 to 2625 mg is shown only for the case of taking the medication after a meal. If valganciclovir taken with food at the recommended dose of 900 mg, increasing to an average AUC24 (approximately 30%) and median Cmax (approximately 14%) of ganciclovir. Therefore, it is recommended to take the drug Valtsit® during meal time (see. The section “Method of administration and dose»).
distribution
Due to the rapid metabolism of valganciclovir to ganciclovir, valganciclovir binding proteins was not determined. ganciclovir plasma protein binding of the drug at concentrations from 0.5 to 51 micrograms / ml of 1-2%. The equilibrium distribution volume after intravenous ganciclovir was 0,680 ± 0,161 l / kg.
metabolism
Valganciclovir is rapidly hydrolyzed to produce ganciclovir other metabolites have been identified. After a single oral 1000 mg ganciclovir radiolabelled indicator radioactivity any of metabolites in feces or urine does not exceed 1-2%.
Withdrawal
The main route of elimination of valganciclovir, ganciclovir as is glomerular filtration and active tubular secretion. In renal clearance accounted 81.5 ± 22% of systemic clearance of ganciclovir.
Pharmacokinetics in special groups of patients
Patients with renal insufficiency
Impaired renal function leads to a decrease in clearance of ganciclovir from the valganciclovir formed, with a corresponding increase in half-life in the terminal phase. Therefore, in patients with impaired renal function dose adjustment is required (see. Sections “Special instructions for dosage” and “Cautions”).
Patients with hepatic insufficiency
Valganciclovir pharmacokinetics was studied in patients with stable graft liver functioning in an open study 4 c-component cross-over design. The absolute bioavailability of ganciclovir from the valganciclovir formed (when taking the drug in a single dose of 900 mg after meals) was approximately 60%, which coincides with the indicator in other patient populations. AUC0-24 ganciclovir was comparable with that after intravenous ganciclovir 5 mg / kg of patients who had undergone a liver transplant.

Active substance:
Valganciclovir

Manufacturer

F.Hoffmann-La Roche Ltd, Switzerland

Composition

1 tablet film coating contains:
active substance: valganciclovir – 450 mg (in the form of valganciclovir hydrochloride – 496.3 mg);
Excipients: povidone K30 – 23.90 mg Crospovidone – 23.90 mg, Microcrystalline Cellulose – 47.80 mg stearic acid – 6.00 mg;
shell – 18.00 mg (hypromellose 2910 – 3 cP, hypromellose 2910 – 6 cps, titanium dioxide (E171), macrogol 400, iron oxide red dye (E172), polysorbate 80); allowed to use the finished mixture Opadry Pink 15V240054

Indications

The treatment of CMV retinitis in adults with AIDS.
Prevention of CMV infection after solid organ transplantation in adults and children over 16 years at risk.

Contraindications

hypersensitivity to valganciclovir, ganciclovir or to any component of the drug. Because of the similar chemical structure of valganciclovir and acyclovir, valacyclovir possible cross-sensitivity reactions to these drugs. Children up to 12 years.
With caution
Older age (safety and efficacy have not been established).

Side effects

These clinical studies

The experience of Valtsita. All adverse events reported in clinical studies Valtsita, previously observed with ganciclovir treatment.

The most common adverse events that occurred while taking valganciclovir in patients with CMV retinitis and AIDS, diarrhea, neutropenia, fever, oral candidiasis, headache and weakness

.

The most common undesirable effects regardless of severity and relation to administration of the drug in patients after organ transplantation: diarrhea, tremors, graft rejection, nausea, headache, lower limb edema, constipation, insomnia, back pain, hypertension, vomiting . Most of them were slightly or moderately expressed. The most common undesirable effects regardless of severity but drug-related (probable or possible relationship) in patients after transplantation sólidnyh organs were: leukopenia, diarrhea, nausea, neutropenia

.

Adverse events that occurred in patients after transplantation with a frequency ≥2% and were not observed in the group of patients with CMV retinitis: hypertension, hypercreatininemia, hyperkalemia, abnormal liver function

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Side effects identified by more than 5% of patients with CMV retinitis and after organ transplantation.

From the digestive tract: diarrhea, nausea, vomiting, abdominal pain, constipation, pain in the upper abdomen, indigestion, abdominal enlargement, ascites, hepatic dysfunction

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The body as a whole: fever, weakness, swelling of the lower extremities, peripheral edema, fatigue, weight loss, decreased appetite, anorexia, cachexia, dehydration, graft rejection reaction

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From the blood and lymphatic system: neutropenia, anemia, thrombocytopenia, leukopenia

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Infectious Complications: oral candidiasis, pharyngitis, nasopharyngitis, sinusitis, upper respiratory tract infections, pneumonia, pneumocystis pneumonia, urinary tract infections

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From the nervous system: headache, insomnia, peripheral neuropathy, paresthesia, tremor, vertigo

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On the part of the skin and its appendages dermatitis, night sweats, itching, acne.

From the respiratory system: dyspnea, productive cough, nasal discharge, pleural effusion

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On the part of the organs of vision: retinal detachment, blurred vision

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From the psychic sphere, depression

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From the musculoskeletal system: back pain, arthralgia, pain in extremities, muscle cramps

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With the genitourinary system: renal impairment, dysuria

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Since the cardiovascular system: hypertension, hypotension

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Laboratory indicators: hypercreatininemia, hyperkalemia, hypokalemia, hypomagnesemia, hyperglycemia, hypophosphatemia, hypocalcemia

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Surgery: postoperative complications, postoperative pain, post-operative wound infection complications, increased wound drainage, poor wound healing

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

From the blood and lymphatic system: pancytopenia, bone marrow suppression function, aplastic anemia. Severe neutropenia (less than 500 cells / ml) was more common in patients during therapy for CMV retinitis (16%) than when assigning patients after organ transplantation (5%).

With the genitourinary system: decrease in creatinine clearance, hypercreatininemia. Increases in serum creatinine observed more frequently in patients after organ transplantation compared with patients who received treatment for CMV retinitis. Impaired renal function – typical complication in transplant patients

.

From the blood (blood, hemostasis): Life-threatening bleeding, possibly associated with the development of thrombocytopenia

.

Part of the central and peripheral nervous system: convulsions, mental disorders, hallucinations, confusion, agitation

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The body as a whole: hypersensitivity to valganciclovir

.

Experience with ganciclovir

Since Valcyte is rapidly converted to ganciclovir, the following are adverse events described in the treatment of ganciclovir, and not mentioned above.

On the part of the digestive organ system: dry mouth, cholangitis, dysphagia, eructation, esophagitis, fecal incontinence, flatulence, gastritis, gastrointestinal disorder, gastrointestinal bleeding, ulcerative stomatitis, pancreatitis, glossitis, hepatitis, jaundice <. / p>

The body as a whole: bacterial, fungal and viral infections, malaise, mucositis, tremors, sepsis

.

On the part of the skin and its appendages: alopecia, exfoliative dermatitis, photosensitivity reactions, dry skin, sweating, urticaria

.

Part of the central and peripheral nervous system: asthenia, headache, nightmares, amnesia, anxiety, ataxia, coma, emotional disorder, hyperkinesia, hypertonia, decreased libido, myoclonic jerks, nervousness, somnolence, disturbances of intelligence

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From the musculoskeletal system: pain in the bones and muscles, myasthenic syndrome

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With the genitourinary system: hematuria, impotence, frequent urination

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Laboratory indicators: increase in activity of alkaline phosphatase, creatine kinase, lactate dehydrogenase in the blood, lowering blood glucose, hypoproteinemia

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From the senses: amblyopia, blindness, ear pain, eye hemorrhage, pain in eyeballs, deafness, glaucoma, a violation of taste perception, non-systemic dizziness, changes in the vitreous

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From the blood and lymphatic system: eosinophilia, leukocytosis, lymphadenopathy, splenomegaly, bleeding

.

Since the cardiovascular system: arrhythmia, including, ventricular, deep vein thrombophlebitis, phlebitis, tachycardia, vasodilation

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On the part of the respiratory system: stagnation in the paranasal sinuses

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From the endocrine system: diabetes

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The experience of the post-marketing use of ganciclovir

The following are undesirable phenomena described in the spontaneous messages during the post-registration application ganciclovir not mentioned in any of the above sections, for which we can not exclude a causal relationship to the drug. Since Valcyte quickly and to a large extent converted to ganciclovir, such adverse reactions can develop in the treatment Valtsitom: anafilakciya, decreased fertility in men

.

Adverse events described under post-registration using the drug are similar to those observed in clinical studies Valtsita and ganciclovir.

How to accept, acceptance rate and dosage

Inside, during a meal time.

In order to avoid an overdose should be strictly observed dosing recommendations.

The standard dosing regimen

Valcyte quickly and to a large extent converted into ganciclovir. Bioavailability of ganciclovir Valtsita 10 times higher than from the capsules of ganciclovir, so it is necessary to adhere strictly to the dosing regime described below Valtsita tablets.

Induction Therapy

in patients with active CMV retinitis Valtsita recommended dose is 900 mg (Table 2. 450 mg), 2 times a day for 21 days. Prolonged induction therapy increases the risk of myelotoxicity.

Supportive therapy

After induction therapy, or in patients with inactive CMV retinitis recommended dose is 900 mg (Table 2. 450 mg), 1 time per day. If for retinitis worsens, induction therapy can be repeated.

Prevention of CMV infection after organ transplantation

transplant patients, the recommended dose is 900 mg (2 tablets of 450 mg), 1 time per day from the 10th day at 100 days after transplant.

Specific guidance on dosing

Patients with renal insufficiency. We must carefully monitor serum creatinine or creatinine clearance. Dose correction is carried out depending on the creatinine clearance, as shown in the table below (see. The sections “Pharmacokinetics in special populations” and “Special instructions»).

Creatinine clearance for males is calculated based on serum creatinine by the following formula:

(140-age in years) × body weight kg) / 72 × 0,011 × serum creatinine, umol / l

women = 0,85 × figure for men.

Creatinine clearance, ml / minDoza for induction terapiiDoza for maintenance therapy / profilaktiki≥60900 mg 2 times a sutki900 1 mg once a sutki40-59450 mg 2 times a sutki450 1 mg once a sutki25-39450 1 mg once a mg every sutki450 dnya10-24450 2 mg every 2 dnya450 mg 2 times a week

Patients on hemodialysis

Patients receiving hemodialysis (creatinine Cl –

Patients with severe leucopenia, neutropenia, anemia, thrombocytopenia or pancytopenia

In patients receiving Valcyte (and ganciclovir), there have been cases of severe leucopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow depression and aplastic anemia. Treatment should not be initiated if the absolute neutrophil count

Storage conditions

At a temperature of not higher than 30 ° C. Keep out of the reach of children.

Active substance

Valganciclovir

Interaction

Drug Interactions Valtsita

The in situ model of intestinal permeability in rats interactions with valganciclovir valaciclovir, didanosine, nelfinavir, cyclosporin, omeprazole and mycophenolate mofetil has been detected.

Valcyte converted to ganciclovir, however interactions characteristic of ganciclovir can be expected when using Valtsita.

Drug Interactions ganciclovir

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

Imipenem-cilastatin: patients treated with both ganciclovir and imipenem / cilastatin, convulsions were observed. Concomitant administration of these drugs should be avoided, unless the potential benefits do not exceed the potential risks.

Probenecid: simultaneous oral administration of probenecid can be about 20% decrease renal clearance of ganciclovir and statistically significant (40%) increase its AUC. This is due to the interaction mechanism – competition for tubular renal excretion. Patients concurrently taking probenecid and Valcyte should be monitored for ganciclovir toxicity.

Zidovudine: the appointment concurrently with oral ganciclovir AUC of zidovudine is not much, but statistically significant increase (17%); In addition, there is a trend, although not statistically significant, in lower concentrations of ganciclovir. Since both zidovudine and ganciclovir can cause neutropenia and anemia, some patients may not tolerate concomitant use of these drugs in full doses.

Didanosine: found that didanosine plasma concentrations while both intravenous and oral administration of ganciclovir steadfastly rising. When receiving ganciclovir oral dose of 3 and 6 g / day of ddI AUC increased by 84-124%, and by intravenous administration of ganciclovir at doses of 5-10 mg / kg / day of ddI AUC increased by 38-67%. This increase can not be explained by competition for renal tubular excretion, as the hatching percentage of didanosine is increased. The reason for this increase may be either increasing bioavailability or metabolism inhibition. Clinically significant effect on ganciclovir concentrations were noted. However, given the increase of plasma concentrations of didanosine in the presence of ganciclovir, patients should be carefully observed for the occurrence of symptoms of toxic action of didanosine.

Mycophenolate mofetil: with the light of a study of a single injection of the recommended dose / ganciclovir and ingestion mycophenolate mofetil, as well as the well-known effect of renal impairment on the pharmacokinetics of ganciclovir and mycophenolate mofetil can be expected that co-administration of these drugs, competing in tubular secretion process, will lead to increased concentrations of ganciclovir, and the phenolic glucuronide of mycophenolic acid (MFKG). Significant changes the pharmacokinetics of mycophenolic acid (IFC) are not expected to adjust the dose of mycophenolate mofetil is required. In patients with impaired renal function, which simultaneously receive mycophenolate mofetil and ganciclovir, it is necessary to comply with recommendations for ganciclovir dose adjustment and careful monitoring.

zalcitabine: zalcitabine increases area under the curve AUC0-8 oral ganciclovir 13%. No statistically significant changes in other pharmacokinetic parameters is not happening. Clinically significant changes in the pharmacokinetics of zalcitabine while oral ganciclovir were also absent, despite a small increase in the elimination rate constant.

Stavudine: while taking stavudine and oral ganciclovir statistically significant pharmacokinetic interaction was observed

.

Trimethoprim: Trimethoprim statistically significantly (16.3%) reduces renal clearance oral ganciclovir, which is accompanied by a statistically significant decrease in terminal elimination rate and corresponding increase in half-life by 15%. However, the clinical significance of these changes is unlikely, since AUC0-8 and Cmax are not changed. The only statistically significant change in trimethoprim pharmacokinetic parameters while taking ganciclovir was an increase in Cmin. However, this is unlikely to have clinical importance, therefore no dosage adjustment is required.

Cyclosporine: Cyclosporine concentrations when compared before taking the next dose data that alters the pharmacokinetics of ganciclovir cyclosporin has been received. However, after the start of ganciclovir there was a slight increase in the maximum level of serum creatinine.

Other possible drug interactions. Purpose ganciclovir concurrently with other drugs that provide myelosuppressive or disruptor effect of renal function (e.g. dapsone, pentamidine, flucytosine, vincristine, vinblastine, adriamycin, amphotericin B, nucleoside analogues and hydroxyurea), may enhance their toxic effects. Therefore, these drugs can be used in conjunction with ganciclovir only if the potential benefits outweigh the possible risk.

Special conditions

In an experiment on animals revealed mutagenic, teratogenic, and carcinogenic spermicidal effect of ganciclovir. Valcyte should be considered a potential teratogen and carcinogenic to humans, the use of which may cause birth defects and cancer. In addition it is likely that Valcyte may temporarily or permanently suppress spermatogenesis.

In patients receiving Valcyte (and ganciclovir), there have been cases of severe leucopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow depression and aplastic anemia. Treatment should not be initiated if the absolute neutrophil count below 500 cells in 1 mm or less platelet count of 25,000 cells / .mu.l, and if hemoglobin level below 8 g / dL.

Do not appoint Valcyte children. Pharmacokinetic properties, safety and efficacy in this population have not been established.

The bioavailability of ganciclovir from Valtsita 10 times higher than that of ganciclovir capsules. Ganciclovir can not be replaced on the rollers in the ratio of 1: 1. Patients who are transferred from ganciclovir capsules should be advised of the risk of overdose if they will accept greater number Valtsita tablets than recommended.

In the course of treatment is recommended on a regular basis to determine the complete blood count with platelets. Patients with severe leucopenia, neutropenia, anemia or thrombocytopenia recommended to appoint hematopoietic growth factors and / or discontinue the drug.

Patients with renal insufficiency Dosage adjustment based on the value of creatinine clearance.

Handling the preparation

The tablets can not crush or pulverize. Since Valcyte is potentially teratogenic and carcinogenic to humans, care should be taken if the tablet fractures. Avoid direct contact faults or crushed tablets with skin or mucous membranes. In cases where such contact is necessary to thoroughly wash it with soap and water; If the product enters the eye, they are washed thoroughly with plain water.

The effect on the ability to drive a car and work with machines and mechanisms. Convulsions, sedation, dizziness, ataxia and confusion, which are described in the treatment of Valtsitom and ganciclovir, may impair the ability to perform tasks that require a certain level of consciousness, including driving and working with machines and mechanisms.

Pregnancy and lactation

Studies of reproductive toxicity with valganciclovir not be repeated due to the rapid and complete conversion of the drug ganciclovir. Ganciclovir violates fertility and is teratogenic in animals.

At the time of treatment should be recommended for women of childbearing age use reliable methods of contraception. Men are recommended to use a barrier method of contraception during treatment and Valtsitom for at least 90 days after the end (see. Section “Preclinical safety data»).

Valtsita safety during pregnancy in humans has not been established. When pregnancy Valtsita destination should be avoided, unless the potential benefit to the mother justifies the potential risk to the fetus.

peri- and postnatal development using valganciclovir and ganciclovir has not been studied, but we can not exclude the possibility of elimination of ganciclovir with breast milk and developing serious adverse reactions in the infant. Therefore, taking into account the potential benefits of therapy Valtsitom to a nursing mother, you must decide on the abolition of the drug or the termination of breastfeeding.

Overdose

One adult patient to use the drug for several days, at doses at least 10 times higher than recommended for him in view of kidney damage (decrease of creatinine clearance), developed bone marrow suppression (medullar aplasia) with a fatal outcome. < / p>

It is possible that an overdose of valganciclovir could manifest signs of renal toxicity.

Reduce valganciclovir plasma concentrations in patients with an overdose can be achieved by dialysis and hydration.

An overdose of ganciclovir when administered intravenously

During clinical studies and post-marketing the drug overdose cases intravenous ganciclovir been described. Some of them were not accompanied by adverse events. The majority of the patients had one or more of the following adverse events:

Hematological toxicity: pancytopenia, bone marrow suppression function, medullary aplasia, leucopenia, neutropenia, granulocytopenia

.

Hepatotoxicity: hepatitis, abnormal liver function

.

Nephrotoxicity: strengthening of hematuria in patients with pre-existing renal disease, acute renal failure, elevated serum creatinine level

.

Gastrointestinal toxicity: abdominal pain, diarrhea, vomiting

.

Neurotoxicity: generalized tremor, convulsions

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