Actas (Actastav)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Dosage form: & nbspcapsules
Composition:

Active substance - Stavudine 30 mg;

Excipients: lactose anhydrous 214.48 mg, sodium carboxymethyl starch 15.0 mg, sodium lauryl sulfate 12.52 mg, magnesium stearate 8.0 mg;

Capsule shell: titanium dioxide 2.1119%, water 14.5%, sodium lauryl sulfate 0.08%, gelatin to 100%, methyl parahydroxybenzoate 0.8%, propyl parahydroxybenzoate 0.2%.

Description:

Hard gelatin capsules No. 2 in white, containing a white powder.

Pharmacotherapeutic group:Antiviral (HIV) agent
Pharmacodynamics:

Stavudine (2'3'-didehydro-3'-deoxythymidine) - a synthetic analogue of thymidine nucleoside, suppresses HIV replication in cultured human cells and in cell lines in vitro. After entering the cage stavudine under the action of cellular enzymes is converted into an active metabolite of stavudine triphosphate, which suppresses the activity of HIV reverse transcriptase due to competition with the natural substrate of dioxytimidine triphosphate and disrupts the replication of HIV. Stavudine triphosphate also enhances the termination of viral DNA chains due to the absence of the 3'-hydroxyl groups in the molecule necessary for constructing DNA. In addition, stavudine triphosphate inhibits cellular DNA polymerases β and γ and markedly reduces the synthesis of mitochondrial DNA.

Pharmacokinetics:

Adults. Stavudine quickly absorbed when taken orally. Absolute bioavailability is about 86.4%. After a single dose of an oral maximum drug concentration (Cmax) in the blood plasma is less than 1 hr. Values Сmах increase in proportion to the increase in doses 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 drug is equally distributed between erythrocytes and leukocytes. Binding to blood proteins is negligible. After a single oral dose of 40 mg, the concentration in the cerebrospinal fluid (CSF) was 63 ng / ml (mean 44-71 ng / ml) for 4-5 hours. The ratio of CSF to plasma concentration is about 40% (mean 31-45%).

After oral administration, the half-life of the drug is 1.4 hours and does not depend on the dose. Renal clearance was 40% of the total clearance, and almost twice the endogenous creatinine clearance, which indicates the active tubular secretion in deriving stavudine through the kidneys along with glomerular filtration.

Children. Absolute bioavailability of the drug in children is an average of 76.9%. The pharmacokinetics after a single dose of the drug is similar to the pharmacokinetics of adults and is independent of dose. Drug concentration in CSF after single and repeated oral administration comprise from 16 to 125% relative to concentration in plasma. Cumulation of stavudine with a dose of 0.125 -2 mg / kg every 12 hours is not observed. Half-life is an average of 1 hour. About 34.5% of the drug is excreted through the kidneys unchanged.

With dysfunction of the kidneys, the clearance of stavudine is reduced. A dose adjustment is recommended (see Dosage and Administration). Patients with impaired liver function in a stable state are not required to adjust the initial dose of the drug.

Indications:

Treatment of HIV infection (in combination with other nucleoside and non-nucleoside reverse transcriptase inhibitors and HIV protease inhibitors).

Contraindications:

Hypersensitivity to stavudine and / or any of the excipients of the drug, children under 3 years (for this dosage form).

Carefully:

Alcoholism,chronic renal failure (creatinine clearance less than 50 ml / min), liver failure, peripheral neuropathy, application in combination with didanosine, pancreatitis.

Pregnancy and lactation:

Use during pregnancy is only possible if the intended benefit to the mother exceeds the potential risk to the fetus.

If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside. The time of taking the drug does not depend on the time of eating. The dose of the drug depends on the body weight.

Body mass

Doses

Adults and children over 12 years of age

≥60kg

40 mg every 12 hours

Children over 3 years old

<30 kg

1 mg / kg every 12 hours

≥ 30kg <60kg

30 mg every 12 hours

If swallowing capsules is difficult, you should gently open the capsule and take the contents with a small amount of food.

Adults with impaired renal function it is recommended to reduce the dose in dependencefrom the creatinine clearance:

Creatinine clearance (ml / min)

Dosage according to body weight

≥60 kg

<60 kg

> 50a

40 mg every 12 hours

30 mg every 12 hoursa

26-50

20 mg every 12 hours

15 mg every 12 hours

< 25b

20 mg every 24 hours

15 mg every 24 hours

a The usual dose, dose adjustment is not required

b Patients after a hemodialysis session are advised to take a daily dose of the drug. On days when dialysis is not performed, the drug should be taken at the same hours as on days conducting hemodialysis.

Children with impaired renal function. Precise recommendations for adjusting the dose of the drug in children are absent. It is possible to reduce the dose and / or increase the interval between doses of the drug.

Side effects:

When used in combination with other drugs with similar toxicity, the risk of side effects increases.

Peripheral neuropathy is a serious and dose-dependent side effect of the drug. The risk of developing this effect increases with simultaneous use with didanosine. Peripheral neuropathy is usually accompanied by a bilateral symmetrical sense of numbness in the limbs: tingling and pain in the soles of the feet and less in the hands. In clinical trials, the frequency of these reactions depended on the dose and / or stage of the disease. In the early stages of the disease, these phenomena are less frequent.

Pancreatitis of various severity, including death, can develop in the patient at different stages of treatment and does not depend on whether the drug is administered as monotherapy or in combination with other drugs, or on the degree of immunosuppression. When using the drug in combination with didanosine or other drugs that have a toxic effect on the pancreas, the risk of developing pancreatitis increases.

Lactic Acidosis. Severe forms of steatosis with hepatomegaly, including death, are noted when nucleoside analogues are used in monotherapy or in combination with other antiviral drugs, including stavudine. With the use of stavudine in combination with didanosine, the risk of liver dysfunction significantly increases. Nausea, vomiting, pain in the abdominal region, rapid breathing or shortness of breath, or muscle weakness may indicate the development of lactic acidosis.

Other side effects: thrombocytopenia, hepatitis, liver dysfunction, asthenia, headache, insomnia, dizziness; dry mouth, decreased appetite, diarrhea, pancreatitis; increased activity of "hepatic" transaminases, hyperbilirubinemia, neutropenia, allergic reactions (skin rash, fever), arthralgia, myalgia, chills.

Children: in clinical trials, the side effects of the drug in sick children and adults were similar. The development of peripheral neuropathy in children was less common than in adults. However, the symptoms of peripheral neuropathy in children were more difficult to identify.

Overdose:

Peripheral neuropathy and impaired liver function.

Treatment: symptomatic.

Stavudine is removed during hemodialysis (removal rate is 120±18ml / min). Peritoneal dialysis is not effective.

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 almost does not bind to blood proteins, which indicates a low probability of drug interactions involving the mechanism of displacement from the binding sites.

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 developing peripheral neuropathy, with progressive HIV infection, with a history of peripheral neuropathy, and when used in combination with didanosine. Feeling numbness, tingling, or pain in the limbs can indicate the development of peripheral neuropathy, which can 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. A dose reduction of up to half the recommended dose may be required.

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. When symptoms of pancreatitis appear, drug treatment should be stopped.With the repeated administration of the drug to exclude the simultaneous use of didanosine and hydroxyurea.

Regardless of how the drug is used, in the form of monotherapy or in combination with other drugs, the biochemical parameters of liver function may increase. For the purpose of early detection of the development of pancreatitis, it is often necessary to check the function of the pancreas.

Form release / dosage:Capsules 30 mg.
Packaging:

For 60 capsules in a plastic bag. 1 packet in a container of high density polyethylene with a lid with a tear-off tab or with a screw cap. For 60 capsules and a bag of silica gel in a container of high density polyethylene with a screw cap made of high-density polyethylene. 1 container with instructions for use in a cardboard box. For 112 cardboard packs, along with instructions for use in a box of 5-ply corrugated cardboard (for hospitals).

Storage conditions:In dry, dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children!
Shelf life:

2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription
Registration number:LSR-002037/08
Date of registration:21.03.2008
Expiration Date:Unlimited
The owner of the registration certificate:AKTAVIS GROUP, AO AKTAVIS GROUP, AO Iceland
Manufacturer: & nbsp
Representation: & nbspACTAVIS GROUP AO ACTAVIS GROUP AO Iceland
Information update date: & nbsp01.07.2017
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