Active substanceStavudineStavudine
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  • Dosage form: & nbspcapsules
    Composition:

    Composition per 1 capsule:

    active substance: Stavudine 30.0 mg;

    Excipients: lactose monohydrate (sugar milk) - 187.6 mg, corn starch - 64.55 mg, magnesium stearate - 2.85 mg.

    Weight of the contents of the capsule: 285.0 mg.

    hard gelatin capsules: the body of white color [titanium dioxide - 2.0%, gelatin - up to 100%], the lid orange [iron oxide yellow - 0.48%, dye sunset yellow (E 110) - 0.15%, gelatin - 100 %].

    Description:
    Capsules number 1, the body is white, the lid is orange. The contents of capsules are white or almost white powder.
    Pharmacotherapeutic group:Antiviral (HIV) agent
    ATX: & nbsp

    J.05.A.F   Nucleosides - reverse transcriptase inhibitors

    J.05.A.F.04   Stavudine

    Pharmacodynamics:
    Stavudine, a synthetic analogue of thymidine nucleoside, suppresses the replication of the human immunodeficiency virus (HIV) in cultured human cells. After entering the cage stavudine under the action of cellular enzymes is converted into an active metabolite - stavudine triphosphate, which suppresses the activity of HIV reverse transcriptase due to competition with the natural substrate thymidine triphosphate. Due to the absence of 3-hydroxyl groups in the molecule necessary for DNA construction, stavudine triphosphate inhibits the synthesis of viral DNA. In addition to reverse transcriptase, the cellular DNA polymerase gamma is also sensitive to inhibition of stavudine triphosphate, while the amount of stavudine is 4000 and 40 times (respectively) greater than the amount of stavudine required to inhibit the cellular DNA polymerases alpha and betta, leading to inhibition of reverse transcriptase .
    Pharmacokinetics:
    Adults. Stavudine quickly absorbed when taken orally. Absolute bioavailability is about 86.4%. After a single dose, the maximum concentration of the drug in the blood plasma (Cmax) is observed in less than 1 hour. The value of Cmax increases in proportion to the increase in the dose of the drug. Cumulation of stavudine in its use every 6, 8 or 12 hours is not observed. The use of the drug after or during meals does not have a significant effect on the pharmacokinetics. The apparent volume of distribution after a single dose of the drug is an average of 46 liters and does not depend on the dose. A small part is associated with plasma proteins, about half - with the shaped elements of the blood. After a single oral dose of 40 mg, the concentration in the cerebrospinal fluid (CSF) averages 63 ng / mL (44-71 ng / mL) for 4-5 hours. The concentration ratio in CSF to plasma concentration is about 40%. Metabolism plays an insignificant role in the clearance of stavudine. After a single or multiple davudine, 34 ± 5% and 40 ± 12% of unchanged stavudine, respectively
    was found in the urine. After oral administration, the half-life (T1/2) is about 2 hours and does not depend on the dose. The total clearance of stavudine in unchanged form is 594 ± 164 ml / min. Stdudine's renal clearance is 237 ± 98 ml / min of apparent overall clearance and almost twice the clearance of endogenous creatinine,which indicates active tubular secretion when deducing stavudine through the kidneys along with glomerular filtration.
    Impaired renal function. There was a decrease in clearance of stavudine with a decrease in creatinine clearance. Dose correction is recommended in patients with impaired renal function (see Fig.
    Method of administration and dose).
    Violation of the function of the liver. Pharmacokinetics of the drug in patients with normal and impaired liver function does not differ significantly. Patients with impaired liver function in a stable state are not required to adjust the initial dose of the drug.
    Children. Absolute bioavailability of the drug in HIV-infected patients aged 5 weeks to 15 years is an average of 76.9%. Pharmacokinetics after a single dose. The administration of the drug is similar to the pharmacokinetics of adults and does not depend on the dose. Concentrations of the drug in the cerebrospinal fluid after a single and multiple oral intake are from 16 to 125% in relation to the concentration in the blood plasma. Cumulation of stavudine with a dose of 0.125-2 mg / kg every 12 hours is not observed. Apparent overall clearance of the drug is 14 ml / min / kg. Half-life is an average of 1 hour.
    Indications:
    Treatment of HIV infection in combination therapy.
    Contraindications:
    • hypersensitivity to stavudine and / or any of the components of the drug;
    • rare hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
    • children with a body weight of less than 30 kg;
    • chronic renal failure with creatinine clearance less than 50 ml / min;
    • simultaneous application with hydroxycarbamide;
    • concurrent use with zidovudine.
    Carefully:Violation of liver function, including chronic hepatitis in the active stage; peripheral neuropathy in history, pancreatitis in the anamnesis, combined use with doxorubicin and ribavirin.
    Pregnancy and lactation:
    Data on use in pregnant women and during lactation are absent. Use during pregnancy is only possible if the expected benefit to the mother exceeds the potential risk to the fetus. If it is necessary to use stavudine during lactation, breastfeeding should be discontinued.
    Dosing and Administration:
    Inside, regardless of food intake. If swallowing capsules is difficult, you should gently open the capsule and take the contents with a small amount of food.
    The dose of the drug depends on the body weight.
    Adults and children with a body weight of at least 30 kg:

    Body mass

    Doses

    > 60 kg

    * 40 mg every 12 hours

    <60 kg

    30 mg every 12 hours

    * When appointing patients with a body weight of more than 60 kg, other dosage forms should be used.
    Application for renal dysfunction
    Adults: dose adjustment is performed depending on the degree of impaired renal function

    Creatinine clearance (ml / min)

    Dosage according to body weight

    ≥60 kg

    <60 kg

    > 50a

    * 40 mg every 12 hours

    30 mg every 12 hoursa

    Usual dose, dose adjustment is not required

    * When appointing patients with a body weight of more than 60 kg, other dosage forms should be used.
    Application for violations of liver function
    With a stable condition of patients with hepatic insufficiency, dose adjustment is not required. With a rapid increase in aminotransferase activity during therapy, therapy should be temporarily discontinued.
    Side effects:
    From the nervous system: depression, peripheral neuropathies, paresthesia, peripheral neuritis, dizziness, pathological dreams, headache, insomnia, drowsiness, pathological thoughts, anxiety, emotional lability, severe muscle weakness (usually with hyperlactatemia or lactic acidosis), fatigue, asthenia;
    From the digestive system: pancreatitis (1%) of varying severity, including fatal cases; diarrhea, abdominal pain, nausea, dyspepsia, vomiting, hepatitis, jaundice, steatosis of the liver, hepatic insufficiency;
    From the endocrine system and metabolism: gynecomastia; diabetes mellitus, hyperglycemia;
    Metabolic disorders: lipoatrophy, lipodystrophy, anorexia; asymptomatic hyperlactatemia; lactic acidosis;
    From the side of blood and blood-forming organs: anemia, neutropenia, thrombocytopenia;
    From the musculoskeletal system: arthralgia, myalgia.
    Allergic reactions: skin rash, itching, urticaria; .
    Children: in clinical trials, the side effects of the drug in children and adult patients were similar. The development of peripheral neuropathy in children was less common than in adults.
    Overdose:
    Doses of the drug, 12 times the recommended daily dose, do not cause acute symptoms in adults.
    Symptoms of chronic overdose: peripheral neuropathy, impaired liver function.
    Treatment: symptomatic.
    Stavudine is removed during hemodialysis (removal rate is 120 ± 18 ml / min). Peritoneal dialysis is ineffective.
    Interaction:
    Stavudine is not recommended for use with zidovudine. The conversion of stavudine to an active metabolite decreases in the presence of zidovudine, stavudine phosphorylation also slows down in the presence of doxorubicin and ribavirin.
    Simultaneously accepted didanosine, lamivudine or nelfinavir do not affect the effectiveness of the drug. The risk of side effects increases with simultaneous use with didanosine.
    Stavudine does not inhibit the main isoforms of cytochrome P450 (CYP1A2, CYP2C9, CYP2D6 and CYP3A4), so davudine interactions with drugs metabolized by these enzymes are unlikely.
    Stavudine almost does not bind to blood proteins, which indicates a low probability of pharmacokinetic interactions with drugs that bind to proteins.
    It is not recommended concomitant use of drugs that cause peripheral neurological disorders (chloramphenicol, cisplatin, dapsone, ethambutol, ethionamide, hydralazine, isoniazid, lithium, metronidazole, nitrofurantoin, phenytoin, vincristine, zalcitabine).
    Special instructions:
    The drug should be used with caution in patients with an increased risk of peripheral neuropathy, with progressive HIV infection, with a history of peripheral neuropathy. The risk of developing this effect increases with simultaneous use in combination with neurotoxic drugs, including didanosine. Feeling of numbness, tingling, or pain in the extremities can indicate the development of peripheral neuropathy. These symptoms may disappear immediately after discontinuation of the drug. If these symptoms occur, you should temporarily stop treatment with the drug. Resumption of treatment with the drug can only be after complete disappearance of symptoms. You may need to adjust the dose of the drug. In addition to the dose of the drug, the frequency of these phenomena depends and / or the stage of the disease (in the early stages are recorded less frequently).
    The drug should be used with caution in patients with an increased risk of developing pancreatitis, with progressive HIV infection, while concomitant administration with didanosine. Pancreatitis of various severity, including cases with a fatal outcome, can develop in the patient at different stages of treatment, regardless of the degree of immunosuppression and dose.When symptoms of pancreatitis appear, drug treatment should be discontinued. When re-appointing the drug to exclude the simultaneous use of didanosine and hydroxycarbamide, the patient should be under close medical supervision. Patients with a pancreatitis in the anamnesis are a special group of risk. For the purpose of early detection of the development of pancreatitis, it is often necessary to check the function of the pancreas.
    Lactoacidosis and severe liver steatosis with hepatomegaly, including fatal cases, are noted when nucleoside analogues are used in combination with other antiretroviral drugs. With the use of stavudine in combination with didanosine, the risk of liver dysfunction significantly increases. Risk factors are female sex, obesity and long-term use of nucleoside analogues. A special group of risk is represented by pregnant women. Signs of the development of symptomatic hyperlactatemia or lactic acidosis can be general fatigue, symptoms of the digestive system (nausea, vomiting, abdominal pain, sudden unexplained weight loss), symptoms from the respiratory system (rapid breathing,shortness of breath), muscle weakness, often associated with symptomatic hyperlactatemia or lactic acidosis syndrome, was rarely noted in the treatment of stavudine. If these symptoms appear, or if laboratory confirmation of lactic acidosis or severe hepatotoxicity is obtained, discontinue drug treatment.
    When using a combination of antiretroviral drugs in combination with hydroxycarbamide, as well as in the administration of stavudine, patients with liver disease should be carefully monitored for patients, if signs of deterioration appear, liver function should be considered, the question of withdrawal of treatment. In connection with the frequency of deaths in the appointment of combined therapy with hydroxycarbamide, didanosine and stavudine, this scheme should be avoided.
    Due to the fact that the clearance of stavudine decreases with a decrease in creatinine clearance, the dose of stavudine for patients with impaired renal function (creatinine clearance ≤ 50 ml / min) should be corrected.
    Redistribution of fatty tissue is observed in patients receiving antiretroviral therapy - obesity by the central type,an increase in the amount of fat in the dorsocervical zone ("buffalo" hump), a decrease in fatty tissue of the limbs and face, a "cushingoid face," an increase in the mammary glands.
    In rare cases, stavudine treatment develops muscle weakness with symptoms similar to the clinical signs of Guillain-Barre syndrome (including respiratory failure). Symptoms may persist or worsen after discontinuation of therapy.
    In patients taking stavudine, especially with prolonged treatment with antiretroviral drugs, there was a case of osteonecrosis, in the etiology of which factors such as treatment with corticosteroids, alcohol abuse, pronounced immunosuppression, obesity play an important role. , A
    There are reports of mitochondrial dysfunction (often transient, anemia, neutropenia, hyperlactatemia, hyperlipazemia) in HIV-negative children exposed to nucleoside analogues in utero or immediately after birth. To later manifestations of this disorder are hypertonic musculature, sudrogs, behavioral anomalies.
    It should be carefully monitored for patients older than 65 years, tk.they represent a group with an increased risk of developing peripheral neuropathy, in addition, this age group has an average higher frequency of renal dysfunction, which should be considered when administering stavudine.
    The immune reactivation syndrome is manifested by the exacerbation of sluggish infections and activation of the opportunistic flora and is also observed at the initial stage of treatment. Patients should be monitored carefully to detect any inflammatory diseases and treat them in a timely manner.
    Effect on the ability to drive transp. cf. and fur:
    The effect of the drug on the ability to drive vehicles and dangerous mechanisms has not been studied, but based on their pharmacodynamics, it can be assumed that it does not affect the ability of concentration of attention.
    Form release / dosage:

    Capsules of 30 mg.

    Packaging:By 7, 10 or 14 capsules in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered. For 28 or 56 capsules in a jar of polymer materials. Each jar or 8 contour cell packs of 7 capsules, or 27 contour mesh packs of 10 capsules, or 4 contour packs of 14 capsules together with the instructions for use are placed in a pack of cardboard.
    Storage conditions:
    At a temperature of no higher than 25 ° C.
    Keep out of the reach of children.
    Shelf life:2 years. Do not use after expiry date.
    Terms of leave from pharmacies:On prescription
    Registration number:P N002941 / 01
    Date of registration:14.08.2008 / 14.03.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia
    Manufacturer: & nbsp
    Information update date: & nbsp02.02.2017
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