Tsivilgan - instructions for use, analogs, reviews and release forms (tablets 450 mg) drugs for the treatment of cytomegalovirus retinitis and other cytomegalovirus infections in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Tsivilgan. There are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors specialists on the use of Tsivilgan in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Tsivilgan with available structural analogues. Use for the treatment of cytomegalovirus retinitis and other cytomegalovirus infections in adults, children, as well as in pregnancy and lactation. Composition of the preparation.

Tsivilgan -Valganciclovir (the active substance of the drug Tsivalgan) is an L-valyl ester (prodrug) of ganciclovir, which is rapidly converted into ganciclovir by intestinal and hepatic esterases after ingestion. Ganciclovir is a synthetic analogue of 2-deoxyguanosine, which suppresses the replication of herpes viruses in vitro and in vivo. Human cytomegalovirus-sensitive viruses include cytomegalovirus (CMV), herpes simplex viruses 1 and 2, human herpesvirus types 6, 7 and 8, the Epstein-Barr virus, the varicella-zoster virus and the hepatitis B virus.

Composition

Valganciclovir hydrochloride + excipients.

Pharmacokinetics

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

The parameters determining the exposure of ganciclovir after taking valganciclovir are bioavailability and renal function. Bioavailability of ganciclovir was similar in all patients receiving valganciclovir. Systemic exposure of ganciclovir for recipients of the heart, kidney, liver transplant was similar to that after oral administration of valganciclovir in accordance with the dosing regimen depending on the function of the kidneys.

Suction and distribution

Valganciclovir is a prodrug of ganciclovir, well absorbed in the gastrointestinal tract, into the intestinal wall, and is rapidly metabolized in the liver with the formation of ganciclovir. Absolute bioavailability of ganciclovir after taking valganciclovir is about 60%.

Due to the rapid metabolism of valganciclovir to ganciclovir, the binding of valganciclovir to plasma proteins was not determined. The binding of ganciclovir to plasma proteins at drug concentrations of 0.5 to 51 μg per milliliter is 1-2%.

Metabolism and excretion

Valganciclovir is rapidly hydrolyzed to form ganciclovir, and no other metabolites have been detected. After a single oral administration of 1000 mg radionuclide-labeled ganciclovir, the radioactivity of none of the metabolites in feces or urine did not exceed 1-2%. Valganciclovir is mostly excreted by the kidneys.

Indications

• treatment of CMV retinitis in patients with AIDS;
• prevention of CMV infection after solid organ transplantation in patients at risk.

Forms of release

The tablets covered with a cover of 450 mg.

Instructions for use and dosing regimen

To avoid overdose, it is necessary to follow the recommendations for the dosing regimen.

Tsivilgan should be taken orally during meals. Valganciclovir is rapidly and largely metabolized with the formation of ganciclovir. Bioavailability of ganciclovir in the case of valganciclovir is 10 times higher than in the case of oral ganciclovir.

Induction therapy of CMV retinitis

In patients with active CMV retinitis, the recommended dose of valganciclovir is 900 mg (2 tablets of 450 mg) twice daily for 21 days. Long-term induction therapy increases the risk of myelotoxicity.

Supportive therapy for CMV retinitis

After the 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

Patients who underwent kidney transplantation should begin valganciclovir therapy within the first 10 days after the operation at a dose of 900 mg (2 tablets of 450 mg) once a day and continue therapy on the 200th day of the posttransplantation period.

Patients who underwent transplantation of other solid organs should begin treatment with valganciclovir within the first 10 days after the operation at a dose of 900 mg (2 tablets of 450 mg) once a day and continue therapy on the 100th day of the post-transplant period.

Special instructions for dosing for patients with renal insufficiency

It is necessary to carry out a careful control of the concentration of creatinine in the blood serum or CC. Dose adjustment in adult patients is carried out depending on KK (ml per minute).

Dose for induction therapy:

• KK more than 60 - 900 mg 2 times a day;
• KK 40-59 - 450 mg twice a day;
• CK 25-39 - 450 mg once a day;
• KK 10-24 - 450 mg every two days;
• QC less than 10 - do not apply.

Dose for maintenance therapy and prevention:

• KK more than 60 - 900 mg once a day;
• KK 40-59 - 450 mg once a day;
• CK 25-39 - 450 mg every two days;
• CC 10-24 - 450 mg twice a week;
• QC less than 10 - do not apply.

Side effect

• Candidiasis of the oral mucosa (fungal infection);
• pharyngitis (inflammation of the mucous membrane of the pharynx);
• sinusitis (inflammation of the mucous membranes of the nasal sinuses);
• pneumonia (pneumonia);
• bronchitis;
• urinary tract infections
• headache;
• dizziness;
• weakness, fatigue;
• insomnia;
• depression;
• sense of anxiety;
• decreased libido;
• nervousness;
• infringement of intelligence;
• amnesia;
• tremor (involuntary trembling of fingers);
• paresthesia (tingling, burning, crawling sensation);
• fever;
• swelling of the lower extremities;
• pain in the limbs;
• muscle cramps;
• back pain;
• arthralgia (joint pain)
• diarrhea, constipation;
• nausea, vomiting;
• stomach ache;
• dyspepsia (indigestion);
• bloating;
• abnormal liver function;
• Cholangitis (inflammation of the bile ducts);
• dysphagia (swallowing disorder);
• eructation;
• esophagitis (inflammation of the esophagus wall);
• fecal incontinence;
• gastritis (inflammation of the gastric mucosa);
• glossitis (inflammatory process in the thickness of the tongue);
• gastrointestinal bleeding;
• ascites (accumulation of free fluid in the abdominal cavity);
• phlebitis (inflammation of the venous wall);
• thrombophlebitis (inflammation of the venous walls with the formation of inflamed veins of thrombi in the lumen);
• neutropenia (a lower level of neutrophils in the blood, leading to a deterioration in the work of immunity);
• anemia (low concentration of hemoglobin);
• thrombocytopenia (decrease in the number of platelets);
• leukopenia (decrease in the number of leukocytes);
• dermatitis;
• night sweats;
• itching;
• acne;
• alopecia (baldness);
• dry skin;
• cough;
• dyspnea;
• discharge from the nose;
• kidney failure;
• dysuria (violation of urination);
• hematuria (blood in the urine);
• frequent urination;
• impotence;
• diabetes;
• arrhythmia (interruptions in contractions of the heart muscle);
• tachycardia (painful heart palpitations);
• decreased appetite;
• decreased body weight;
• anorexia (complete absence of appetite);
• cachexia (severe weight loss, extreme exhaustion);
• dehydration (dehydration);
• decrease or increase in blood pressure;
• amblyopia (low vision);
• blindness;
• earache;
• hemorrhage in the eye;
• Pain in the eyes;
• glaucoma (eye disease caused by increased intraocular pressure);
• deafness;
• noise in ears;
• violation of taste perception;
• Hyperkalemia (high potassium content);
• hypokalemia (low potassium content);
• hypomagnesemia (decrease in magnesium concentration in the body);
• hyperglycemia (high glucose)
• hypophosphatemia (decrease in the level of phosphates in the blood);
• hypocalcemia (low calcium content);
• hypercreatininaemia (increased level of creatinine in the blood);
• pain in the postoperative period;
• infection of a postoperative wound;
• poor healing of the postoperative wound.

Contraindications

• increased sensitivity to valganciclovir, ganciclovir or any of the components of the drug. Because of the similar chemical structure of acyclovir, valaciclovir and valganciclovir, cross-sensitivity reactions to these drugs are possible;
• the absolute number of neutrophils is less than 500 cells per 1 μl, the platelet count is less than 25,000 cells per 1 μl or the hemoglobin concentration is below 80 grams per liter;
• KK (creatinine concentration) is less than 10 ml per minute;
• children's age till 18 years.

Application in pregnancy and lactation

During treatment with Tsivilgan, women of childbearing age should be recommended to use reliable methods of contraception, men are recommended to use barrier method of contraception during treatment and not less than 90 days after its termination.

Safety of the use of Tsivilgan in pregnancy in humans is not established. In pregnancy, valganciclovir should be avoided, except when the potential for the mother justifies the possible risk to the fetus.

Studies of the effects of valganciclovir and ganciclovir on peri- and postnatal development have not been carried out, and the possibility of isolating ganciclovir with breast milk and developing serious adverse reactions in the infant can not be ruled out. Thus, the decision to discontinue the drug or stop breastfeeding should be taken based on an assessment of the potential positive effect of treatment for the nursing mother and the risk to the infant.

Use in children

The use of the drug for children and adolescents under the age of 18 is contraindicated.

Application in elderly patients

Caution should be used with elderly patients.

special instructions

In animal experiments, mutagenic, teratogenic, aspermatogenic and carcinogenic effects of ganciclovir have been identified. Valganciclovir should be considered a potential teratogen and a carcinogen for a person whose use can cause congenital malformations and cancer. In addition, it is likely that valganciclovir can temporarily or irreversibly inhibit spermatogenesis.

In patients receiving Tsivilgan (and ganciclovir), cases of severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, oppression of bone marrow function and aplastic anemia have been observed.Treatment should not be started if the absolute number of neutrophils is less than 500 cells per 1 μl or the platelet count is less than 25,000 cells per 1 μl, and also if hemoglobin is below 80 grams per liter.

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

With simultaneous application of ganciclovir with imipenem and cilastatin, patients had convulsions. Avoid simultaneous use of valganciclovir with imipenem, cilastatin in cases where the potential benefits of treatment do not exceed the possible risk.

Since both zidovudine and ganciclovir can cause neutropenia and anemia, some patients may experience intolerance with concurrent administration of Zyvalangan and zidovudine in full doses.

In connection with 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 concomitantly with other drugs that have a myelosuppressive or nephrotoxic effect may enhance their toxic effects.

Bioavailability of ganciclovir from valganciclovir is 10 times higher than that of ganciclovir capsules. Ganciclovir can not be replaced with valganciclovir in a 1: 1 ratio. Patients who are transferred from ganciclovir capsules should be informed of the risk of overdose if they take more valganciclovir tablets than recommended.

Rules for handling the drug

Tablets can not be broken or crushed. Since valganciclovir is potentially teratogenic and carcinogenic to humans, care must be taken if the tablet breaks down. Do not directly contact broken or crushed tablets with skin and mucous membranes. In cases of such contact, it is necessary to thoroughly wash this area with soap and water, if it gets into the eyes - they are thoroughly washed with sterile water, and in its absence - with plain water.

Impact on the ability to drive vehicles and manage mechanisms

In the treatment of valganciclovir or ganciclovir, seizures, sedation, dizziness, ataxia, or confusion may occur, which can adversely affect activities requiring increased concentration of attention, including vehicle management and work with machines and mechanisms. Therefore, during the period of Tsivilgan treatment, care should be taken when driving a vehicle and working with machines and mechanisms. When dangerous undesirable phenomena appear, one should refrain from performing these activities.

Drug Interactions

On the model of intestinal permeability in situ in rats, the interactions of valganciclovir with valacyclovir, didanosine, nelfinavir, cyclosporine, omeprazole, and mycophenolate mofetil were not detected.

Valganciclovir is converted to ganciclovir, so interactions that are characteristic of ganciclovir can also occur with valganciclovir.

Drug Interactions of Ganciclovir

The degree of binding of ganciclovir to plasma proteins is only 1-2%, so reactions related to substitution of protein binding are not expected.

Imipenem + cilastatin - with simultaneous application of ganciclovir with imipenem and cilastatin, patients had convulsions.

Probenecid - simultaneous oral administration of probenecid resulted in a statistically significant decrease in renal clearance of ganciclovir (20%) and an increase in the duration of its action (40%). The ego is explained by the mechanism of interaction - competition for tubular renal excretion. Patients taking both probenecid and valganciclovir simultaneously should be closely monitored because of the possible toxic effects of ganciclovir.

Zidovudine - with simultaneous use with oral ganciclovir, there was a small but statistically significant increase in zidovudine AUC (17%). In addition, there was a statistically insignificant tendency to reduce the concentration of ganciclovir. Since both zidovudine and ganciclovir can cause neutropenia and anemia, some patients may experience intolerance while taking valganciclovir and zidovudine in their entire doses.

Didanosine - a persistent increase in the concentration of didanosine in plasma with a simultaneous application with ganciclovir (both with intravenous and oral administration) has been identified.In the case of oral administration of ganciclovir in a dose of 3 and 6 grams per day, there was an increase in didanosine AUC by 84-124%, with intravenous administration of ganciclovir in doses of 5-10 mg per kilogram per day of didanosine AUC increased by 38-67%. This increase can not be explained by the competitive interaction for renal tubular excretion, as the percentage excretion didanosine increased in this case. The reasons for this increase may be an increase in bioavailability or a slowing of metabolism. There was no clinically significant effect on the concentration of ganciclovir. However, given the increase in plasma concentrations of didanosine in the presence of ganciclovir, patients should be closely monitored for symptoms of toxic effects of didanosine when valganciclovir is used.

Mycophenolate mofetil - based on the results of a single intravenous administration of the recommended dose of ganciclovir and oral administration of mycophenolate mofetil, as well as the known effect of renal dysfunction on the pharmacokinetics of mycophenolate mofetil and ganciclovir, simultaneous use of valganciclovir and mycophenolate mofetil,which have a competitive interaction in the process of tubular secretion, will lead to an increase in the concentration of ganciclovir and phenolic glucoronide of mycophenolic acid. A significant change in the pharmacokinetics of mycophenolic acid is not expected, so adjust the dose of mycophenolate mofetil is not required. In patients with impaired renal function, which simultaneously receive mycophenolate mofetil and valganciclovir, it is necessary to follow the recommendations for correcting the dose of valganciclovir and to carry out careful monitoring.

Zalcitabine-zalcitabine increased AUC0.8 orally ganciclovir by 13%. No statistically significant changes in other pharmacokinetic parameters were noted. Clinically significant changes in the pharmacokinetics of zalcitabine with simultaneous oral administration of ganciclovir were also not detected, despite a slight increase in the elimination rate constant.

Stavudine - with simultaneous oral administration of ganciclovir and stavudine no statistically significant pharmacokinetic interaction was noted.

Trimethoprim-trimethoprim statistically significant by 16.3% reduced the renal clearance of ganciclovir, taken orally,which was also accompanied by a statistically significant decrease in the rate of terminal elimination and a corresponding increase in the half-life of 15%. Nevertheless, the clinical significance of these changes is unlikely, since AUC0-8 and the maximum concentration did not change. The only statistically significant change in trimethoprim pharmacokinetic parameters while taking ganciclovir was an increase in the minimum concentration of 12%. However, this is unlikely to be of clinical importance, therefore, valganciclovir dose adjustment is not required.

Cyclosporine - when compared to cyclosporine concentration before taking the next dose data that ganciclovir altered pharmacokinetics cyclosporin has been received. Nevertheless, after the initiation of ganciclovir, there was a slight increase in the maximum serum creatinine concentration.

Other possible drug interactions - ganciclovir concurrently with other drugs that provide nefrotoksichssky or myelosuppressive effect (e.g., dapsone, pentamidine, flucytosine, vincristine, vinblastine, adriamycin, amphotericin B, nucleoside analogues and hydroxycarbamide), may enhance their toxic effects.Therefore, these drugs can be used concomitantly with valganciclovir only if the expected benefit of the treatment exceeds the possible risk.

Analogues of the drug Tsivalgan

Structural analogs for the active substance:

• Valganciclovir;
• Valcitol.

Analogues for the pharmacological group (antiviral drugs):

• Avonex;
• Aktaviron;
• Alloferon;
• Alpisarin;
• Algeron;
• Altevir;
• Alfaferon;
• Amizon;
• Amiksin;
• Arbidol
• Arviron;
• Arpefly;
• Afludol;
• Acigerpine;
• Acyclovir;
• Acyclostad;
• Aeros;
• Bonaphoton;
• Valaciclovir;
• Valacitek;
• Valtrex;
• Valtsikon;
• Wartocide;
• Vacrex;
• Vectavir;
• Vivorax;
• Virazole;
• Virolex;
• Viferon;
• Genfaxon;
• Gervirax;
• Gerpevir;
• Gerperax;
• Devirs;
• Zovirax;
• Isoprinosine;
• Imiquimod;
• Ingavirin;
• Inter;
• Inferon;
• Yodantipyrine;
• Lavomax;
• Ladivin;
• Layfferon;
• Lacrinate;
• Lamuzide;
• Lysavir;
• Lokferon;
• The Medovar;
• Minaker;
• Nevirapine;
• Neovir;
• Nomides;
• Oxolin;
• Orvire;
• Panavir;
• Provirsan;
• Realdiron;
• Rebetol;
• Remantadine;
• Ribavin;
• Ribavirin;
• Ribamidyl;
• Ribapeg;
• Riluzole;
• Rimantadine;
• Ronbetal;
• Roferon;
• Supperan;
• Tamiflu;
• Thilaxin;
• Fawirox;
• Famacivir;
• Familar;
• Famciclovir;
• Fenistil;
• Cyclovax;
• Cyclovir.

Response of infectious diseases physician

Tsivilgan is an effective antiviral medicine. Its active active substance valganciclovir is active in relation to cytomegalovirus, herpes simplex virus, hepatitis B virus, varicella virus. Tsivilgan is most often prescribed for the treatment of cytomegalovirus retinitis in AIDS patients. When taking Tsivilgan, serious side effects can develop - the list is quite large. Therefore, in order to minimize their occurrence, all recommendations on the dosage regimen should be strictly observed.

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