Видекс®

General characteristics. Structure:

Active ingredient: 125 mg, 250 mg or 400 mg of a didanozin.

Excipients: carboxymethylstarch of sodium, a karmelloz of sodium, water the cleared q.s. (is removed in the course of production).

Structure of a kishechnorastvorimy cover of granules: methacrylic acid and an etakrilat copolymer [1:1], diethyl phthalate, water the cleared q.s. (is removed in the course of production), sodium q.s hydroxide.

Excipients: talc.

Structure of a cover of the capsule: sodium lauryl sulfate, titanium dioxide, gelatin.

The structure blackened:

- capsules of 125 mg - shellac, ethanol anhydrous (is removed in the course of production), isopropanol (is removed in process - productions), butanol (is removed in the course of production), propylene glycol, ammonia water, potassium hydroxide, the water purified titanium dioxide (E171), dye ferrous oxide red (E172), dye ferrous oxide yellow (E172);

- capsules of 250 mg - shellac, ethanol anhydrous (is removed in the course of production), isopropanol (is removed in the course of production), butanol (is removed in the course of production), propylene glycol, ammonia water, indigo carmine (E132);

- capsules of 400 mg - shellac, dye ferrous oxide red (E172), isopropanol (is removed in the course of production), butanol (is removed in the course of production), propylene glycol, ammonium hydroxide, симетикон.

Pharmacological properties:

Pharmacodynamics. Didanozin (2,3-didezoksiinozin or ddl) - a synthetic analog of a nucleoside of a dezoksiadenozin, inhibits the HIV return transcriptase. It is proved what диданозин suppresses replication of HIV in the cultivated cells of the person and in the cellular in vitro lines.

After hit in a cell диданозин under the influence of cellular enzymes didezoksiadenozin-5-triphosphate (DDATF) turns into an active metabolite. At replication of nucleic acid of a virus inclusion of a 2,3-didezoksinukleozid

The active metabolite of DDATF suppresses activity of the return VICh-1 transcriptase due to the competition to dezoksiadenozin-5-triphosphate (DATF) for linkng with active sites of enzyme. Contacting the active site of enzyme, it interferes with growth of a chain and, thereby, suppresses replication of a virus.

Pharmacokinetics. Absorption. After intake диданозин it is quickly soaked up, the maximum concentration in a blood plasma (Cmax) of a dozozavisim at reception in the form of capsules and is noted by a dosage to 400 mg in 30-90 minutes. Bioavailability makes about 42%.

The area under a curve concentration - time (AUC) in an equilibrium state averages 2,60 mg x h/l for adult patients and children, At use of capsules with greasy food of Cmax and AUC value decrease by 46% and 19% respectively. The seeming distribution volume - on average about 300 l for adults and 100 l - for children. Linkng with proteins of plasma - no more than 5%.

Metabolism. Metabolism of a didanozin at the person is not studied. According to researches on animals it is supposed that at the person it occurs on the way of metabolism of endogenous purines.

Removal. After oral administration the elimination half-life of a didanozin averages 1,2 hours, in urine about 20% of the accepted dose are found. The clearance makes about 175 l/h for adults and 90 l/h for children.

The renal clearance makes 50% of the general clearance (800 ml/min.) that indicates active canalicular secretion at removal of a didanozin through kidneys along with glomerular filtering.

Pharmacokinetics at a renal failure. After oral administration the elimination half-life increases on average of 1,4 o'clock at patients with normal function of kidneys till 4,1 o'clock at patients with heavy renal failures. In peritoneal dialysis liquid диданозин it is not found out while during a hemodialysis in 3-4 hours of concentration of a didanozin make 0,6-7,4% of the entered dose. Absolute bioavailability does not change at patients with heavy renal failures, in comparison with patients with normal function of kidneys, however the clearance of a didanozin decreases in proportion to clearance of creatinine.

Pharmacokinetics at an abnormal liver function. Average Cmax and AUC values at patients with abnormal liver functions were slightly higher (13% and 19%, respectively), than at healthy patients, however correction of doses for this category of patients is not required as patients with abnormal liver functions and without them had an identical dispersion of individual indicators.

Pharmacokinetics at children and teenagers. During studying of pharmacokinetics at children aged from 1 year up to 17 years absorbability of a didanozin changed with the broad range. Despite it, Cmax and AUC values increased in proportion to a dose. Absolute bioavailability of a didanozin at oral administration of drug made about 36% after the first dose and 47% in an equilibrium state.

The elimination half-life averages about 0,8 hours. After the first peroral dose of concentration of a didanozin in urine made 18% and 21% in steady state. Renal clearance about 243 ml/sq.m/min. that made 46% of the general clearance of an organism. As well as at adults, at children active tubular secretion was observed. At oral administration of drug within 26 days of cumulation of a didanozin at children it is not observed.

Indications to use:

Treatment of VICh-1 of an infection (in a combination with other anti-retrovirus drugs).

Route of administration and doses:

Features of use:

Pregnancy and lactation. Adequate and controlled researches at pregnant women were not conducted. It is necessary to apply during pregnancy only in the presence of strict indications and only when the potential advantage for mother outweighs possible risk for a fruit. During treatment by drug breastfeeding should be stopped.

Communication between sensitivity of HIV to a didanozin in vitro and the clinical response to treatment is not established. Results of definition of sensitivity of in vitro vary with the broad range. Positive correlation of in vivo between results of measurements of virus activity (for example, definition by method of polymerase chain reaction of HIV RNA) and clinical progressing of a disease is established. Purpose of drug is recommended to children up to 3 years only in the form of suspension. At simultaneous use of the drug Videks® with medicines with toxic action on
peripheral nervous system or pancreas the risk of manifestation of these toxic effects considerably increases.

At simultaneous use of pentamidine intravenously or the drugs increasing activity of a didanozin (a hydroxycarbamide, Allopyrinolum) therapy by the drug Videks® is recommended to be suspended.

Vision disorders. It is necessary to check periodically sight and to note any vision disorders, such as the changed perception of color or indistinct vision of objects. Children should conduct examination of a retina each 6 months or at emergence of any changes of sight. The decision on change of therapy can be made on the basis of inspection of the patient and assessment of the relation advantage/risk.

Liver diseases. A hepatotoxic and a liver failure from the death were noted in post-market researches at HIV-positive patients during the combined anti-retrovirus therapy together with a hydroxycarbamide. Cases of an abnormal liver function from the death were noted at such patients at a primeneniikombination a hydroxycarbamide, диданозин and ставудин in this connection it is necessary to avoid combined use of these drugs. Efficiency and safety of the drug Videks® at patients with serious violations of work of a liver in the anamnesis are not established. During the combined anti-retrovirus therapy at such patients, including at patients with active chronic hepatitis, the frequency of abnormal liver functions, including heavy and potentially life-threatening, increases. Observation of a condition of such patients has to be made according to standard practice. In case of an aggravation of symptoms of such patients, and also at increase in activity of "hepatic" enzymes above of clinically significant level therapy by the drug Videks® has to be suspended or cancelled.

Immunity recovery syndrome. HIV-positive patients with the expressed immunodeficiency during the combined anti-retrovirus therapy can have signs of inflammatory reaction to asymptomatic or residual opportunistic infections. This syndrome was observed within the first several weeks or months after the beginning of anti-retrovirus therapy. Emergence of signs of Cytomegaloviral retinites, generalized or focal mikobakterialny infections and the pneumonia caused by Pneumocystis jiroveci is possible. If necessary the corresponding therapy is appointed. The cases of autoimmune diseases (for example, Greyvs's disease) arising at immunity recovery were noted, however time of the beginning of development of such diseases varied at different patients and could come in many months after the beginning of therapy.

Redistribution/accumulation of a fatty tissue (lipodystrophy / lipoatrophia). At the patients receiving anti-retrovirus therapy cases of redistribution/accumulation of a fatty tissue were noted (lipodystrophy/lipoatrophia) that was shown by obesity on the central type, increase in quantity of a fatty tissue in a dorsotservikalny zone ("a buffalo hump"), reduction of quantity of a fatty tissue of extremities and persons, increase in a breast, "a cushingoid face".

Pancreatitis. Pancreatitis is heavy toxic effect of use of drug. Pancreatitis of varying severity, it is frequent with a lethal outcome, can develop at the patient at different stages of treatment and does not depend on whether drug in the form of monotherapy or in a combination with other drugs, or from immunosuppression degree is used. Pancreatitis is a dozozavisimy complication. The patients accepting the drug Videks® in a combination with stavudiny a hydroxycarbamide, are subject to higher risk of development of this side effect. The risk of development of pancreatitis increases at elderly patients, at patients with pancreatitis in the anamnesis, with a renal failure at otsutstviisootvetstvuyushchy corrections of a dose of drug, and also at patients with progressing HIV - an infection.

At patients with risk factors of development of pancreatitis the drug Videks® should be used with care. At emergence of symptoms of pancreatitis treatment by drug should be suspended, and at confirmation of the diagnosis treatment should be stopped. At clinically significant exceeding of maintenance of biochemical markers, even in the absence of pancreatitis symptoms, treatment also should be suspended.

Lactate acidosis / the Severe form of a steatosis with a hepatomegalia. Lactate acidosis / the Severe form of a steatosis with a hepatomegalia, including with a lethal outcome, are noted at use of nukleozidny inhibitors of the return transcriptase at monotherapy or in a combination with other anti-retrovirus drugs, including диданозин. Generally this side effect was observed at women. Obesity and long reception of nukleozidny inhibitors of the return transcriptase can serve as risk factors of emergence of this side effect. At pregnant women the risk of development of a lactacidemia with a lethal outcome increases at reception of a didanozin in a combination with stavudiny or other anti-retrovirus drugs. In this regard it is possible to apply a combination of these drugs at pregnant women with extreme care.

At emergence of clinically confirmed symptoms of a hepatotoxic or a lactacidemia (which can include a hepatomegalia and a steatosis even in the absence of strong indications of increase in activity of "hepatic" transaminases), treatment by drug should be suspended. At considerable exceeding of activity of "liver enzymes" and bilirubin (increase 3-4 degrees: 5 times higher than norm for "hepatic" transaminases and an alkaline phosphatase; twice higher than norm for a lipase; 2,6 times higher norms for bilirubin) treatment should be stopped.

Portal hypertensia, untied with cirrhosis. In post-market researches cases of portal hypertensia, untied with cirrhosis, including the cases leading to transplantation of a liver, and also by the deaths were noted. The portal hypertensia, untied with cirrhosis, caused by reception of a didanozin was confirmed at patients with an unconfirmed viral hepatitis. The first symptoms and symptoms of portal hypertensia appeared during the period from several months to several years after the beginning of therapy didanoziny. The general signs of development of portal hypertensia included: increase in activity of enzymes of a liver, gullet varicosity, hematemesis, ascites, splenomegaly. The patients accepting диданозин have to be inspected regularly on existence of precursory symptoms of portal hypertensia (for example, thrombocytopenia and a splenomegaly) during the planned visits to the doctor. The corresponding laboratory researches including a research of activity of a fermentovpechena, concentration of bilirubin, albumine in serum the developed blood test, the international normalized relation (MHO) and an ultrasonografiya, have to be appointed to such patients. Administration of drug of Videks® has to be stopped at emergence in the patient of symptoms of the portal hypertensia which is not connected with cirrhosis.

Peripheral neuropathy. Peripheral neuropathy usually is followed by bilateral symmetric feeling of numbness of extremities: a pricking and pains in feet and, more rare, in brushes. At early stages of a disease these phenomena meet less often.

There is information that the course of peripheral neuropathy can be burdened at joint reception of anti-retrovirus drugs, including диданозин, ставудин, and a hydroxycarbamide. At emergence of the phenomena of peripheral neuropathy it is necessary to suspend therapy didanoziny before their elimination. After elimination of the specified symptoms the patient can accept a reduced dose of drug.

Didanozin quickly collapses in acid contents of a gastric juice. In capsules диданозин contains in a type of the granules covered with a kishechnorastvorimy cover owing to what absorbability of a didanozin in intestines increases. Absorbability of a didanozin irrespective of a dosage form in the presence of food decreases on average by 50%. At purpose of drug the patients who is on a diet with salt consumption restriction should consider that in 100 mg of contents of capsules not less than 0,424 mg of sodium contain.

Does not contain sucrose therefore there are no restrictions for drug use with a sick diabetes mellitus.

Influence on ability to manage vehicles and mechanisms. The special researches studying influence of the drug Videks® on ability to manage vehicles and mechanisms were not conducted.

Side effects:

From the alimentary system and a liver: anorexia, dyspepsia, nausea, vomiting, abdominal pains, diarrhea and the increased gas generation, hepatitis, a liver failure, the portal hypertensia which is not connected with cirrhosis, pancreatitis, lactic acidosis / a severe form of a steatosis with a hepatomegalia, a hypertrophy of a parotid sialaden, a sialadenitis, a lipodystrophy, a lipoatrophia.

From a nervous system: peripheral neuropathy, paresthesias, pain in brushes and feet, a headache.

From sense bodys: dryness in a mouth, a xerophthalmus, an optic neuritis, a retina depigmentation.

From a musculoskeletal system: a mialgiya (with increase or without increase in level of a creatine kinase), an arthralgia, a myopathy, рабдомиолиз.

From bodies of a hemopoiesis: anemia, granulocytopenia, leukopenia, thrombocytopenia.

Side effects at a combination therapy

At simultaneous use of a didanozin and drugs with a similar profile of toxicity (a stavudin and/or a hydroxycarbamide) such side effects as pancreatitis, a hepatotoxic (including fatal), and also a heavy peripheral neuropathy are noted more often than for lack of such modes of treatment.

Laboratory indicators: hypo - and a hyperpotassemia, a giperurekimiya, increase in activity of amylase and a lipase, increase in activity of "hepatic" transaminases and an alkaline phosphatase, a hyperbilirubinemia, hypo - and a hyperglycemia.

Others: diabetes mellitus, alopecia, anaphylactoid/allergic reactions, adynamy, fatigue, fever/fever, itch, skin rash.

Children. Side effects of drug at children and adult patients are similar. Development of pancreatitis in children is observed in 3% of cases at reception in the doses which are not exceeding recommended and in 13% - at treatment by the raised drug doses. Vision disorders are observed at children in rare instances and characterized by changes in a retina and an optic neuritis.

Interaction with other medicines:

At use of a didanozin with other drugs with similar toxicity (for example, with stavudiny) the risk of development of the described side effects considerably increases in a combination. The risk of development of pancreatitis can increase in proportion to the increase in concentration of a didanozin caused by combined use of the drug Videks® and Allopyrinolum. In this regard contraindicated combined use of Allopyrinolum and drug Videks®.

Methadone. At use of powder of a didanozin for patients with opioid dependence against the background of prolonged treatment with methadone observes reduction of AUC value of a didanozin by 57%. At simultaneous use of drugs the dose of the drug Videks® should be raised. Researches for studying of possible interaction of methadone and the drug Videks® capsules were not conducted.

Tenofovir. At combined use increase in concentration of a didanozin in plasma therefore the dose of drug needs to be adjusted is observed: for adults with body weight not less than 60 kg and clearance of creatinine not less than 60 ml/min. - 250 mg once a day along with easy food (no more than 400 kcal, with the content of fat no more than 20%) or on an empty stomach; for adults with body weight less than 60 kg and clearance of creatinine not less than 60 ml/min. - 200 mg once a day. In this case administration of drug in the form of powder for preparation of solution for intake is recommended. Recommendations about use depending on meal are specified in the instruction to the drug Videks®, powder for preparation of solution for intake.

Delavirdin or индинавир it is necessary to accept in 1 hour prior to reception of powder of a didanozin. In the presence of a didanozin AUC value of a delavirdin or indinavir considerably increases. Medicinal interaction between indinaviry and didanoziny in capsules is not revealed.

In special researches of repeated use of a dose of drug along with drugs dapsone, not Virapinum, рифабутин, foskarnt, ритонавир, ставудин and a zidovudine and single use of a dose of drug along with drugs loperamide, Metoclopramidum, ranitidine, sulfamethoxazole, Trimethoprimum of medicinal interactions is not revealed.

Ketokonazol or итраконазол absorbability of which at oral administration influences acidity of a gastric juice, it is necessary to accept in 2 hours prior to reception of powder of a didanozin. The Videks® capsules do not contain antacids therefore the risk of interaction of these drugs is absent.

At administration of drug of Videks® (powder) in 2 hours prior to reception of a gantsiklovir or along with it AUC indicator in an equilibrium condition of a didanozin increases on average to 111%. Insignificant reduction of AUC in an equilibrium state (for 21%) a gantsiklovir was noted when patients accepted Videks® in 2 hours prior to a gantsiklovir. Changes of renal clearance for one of these two drugs were not observed. It is unknown whether these changes are connected with changes of safety of use of the drug Videks® or efficiency of use of ганцикловира.Нет of the data confirming strengthening didanoziny myelosuppressive effects of a gantsiklovir.

In the absence of a suitable alternative to a gantsiklovir it is recommended to apply it with care at co-administration with the drug Videks® in capsules. It is necessary to control emergence of the toxic effects connected with didanoziny.

Concentration of antibiotics of a tetracycline row and some antibiotics of a ftorkhinolonovy row (for example, ciprofloxacin), in a blood plasma decrease in the presence of antacids as form chelate connections. In this regard the powder dissolved in suspension of antacids should be accepted, at least, in 6 hours prior to or in 2 hours after ciprofloxacin reception. The Videks® capsules do not contain antacids therefore the risk of interaction with antibiotics of tetracycline and ftorkhinolonovy ranks is absent.

Ribavirin can increase the content of intracellular triphosphates of a didanozin and potentially increase risk of side effects. At combined use of a didanozin with ribaviriny in a combination with stavudiny or without it it was reported about cases of a liver failure with a lethal outcome, and also about cases of pancreatitis, peripheral neuropathy and a symptomatic giperlaktatemiya / lactacidemia. In this regard contraindicated combined use of a didanozin and ribavirin.

The medicines possessing neurotoxic action. At combined use with didanoziny it is necessary to be careful in view of increase in risk of development of neuropathy. Clinically significant changes of pharmacokinetic parameters of a nelfinavir at reception together with easy food in 1 hour after a didanozin in the form of powder were not observed. Less than 5% of a didanozin are in the connected state with proteins of a blood plasma, indicating small probability of medicinal interactions with participation of the mechanism of replacement from places of binding.

Contraindications:

- Hypersensitivity to a didanozin and/or any of drug excipients,

- Simultaneous use with Allopyrinolum, ribaviriny,

- Breastfeeding period,

- Children's age up to 3 years and with a body weight up to 25 kg (for this dosage form; use of drug in the form of powder for preparation of solution for intake is recommended).

With care. Drug should be used with care at patients with the increased risk of development of pancreatitis, with pancreatitis in the anamnesis, patients with risk factors have development of lactic acidosis (obesity, prolonged treatment by nucleotide analogs), at the progressing HIV infection, with a peripheral neuropathy in the anamnesis, at the patients accepting neurotoxic medicines (the increased risk of development of a peripheral neuropathy) at elderly patients, at treatment of patients with an impaired renal function with not corrected drug doses, at patients with diseases of an organ of sight (in view of danger of development of neuritis and changes of a retina). With special care it is necessary to apply at patients with the broken function of a liver in view of risk of development of a heavy hepatomegalia with a steatosis.

Overdose:

There is no antidote at overdose of a didanozin. The main manifestations at drug overdose: pancreatitis, peripheral neuropathy, hyperuricemia, abnormal liver functions.

Treatment: symptomatic, control of the main vital functions is necessary.

Didanozin does not leave from an organism peritoneal dialysis and very few hemodialysis. During sessions of a gemodiliz lasting 3-4 hours about 25-30% of a didanozin of the general concentration of a didanozin circulating in blood by the beginning of carrying out a hemodialysis are removed.

Storage conditions:

At a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to accept after a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 10 capsules in the blister from PVC / aluminum foil. 3 blisters together with the application instruction in a cardboard pack.