Stag - instructions for use, doses, side effects, contraindications

active substance - Stavudine 30.0 mg; Excipients - lactose monohydrate 60.0 mg, lactose 96.0, cellulose microcrystalline 27.0 mg, magnesium stearate 3.0 mg, sodium carboxymethyl starch (Primogel) 9.0 mg;

capsules hard gelatinous №2:

gelatin - q.s. up to 100%, titanium dioxide - 0.6500%, iron oxide colorant yellow - 0.5333%, iron oxide dye red - 0,0667%, ink for inscription (shellac, dye iron oxide black, propylene glycol, ammonia) - 15 mcg;

active substance - Stavudine 40.0 mg; Excipients - lactose monohydrate 80.0 mg, lactose 128.0 mg, microcrystalline cellulose 36.0 mg, magnesium stearate 4.0 mg, toarboxymethyl starch sodium (primogel) 12.0 mg;

capsules hard gelatinous №1: gelatin - q.s. up to 100%, titanium dioxide 0.7583%, iron dye oxide yellow 0.5067%, ferric oxide red oxide 0.33333%, inscription ink (shellac, iron oxide oxide black, propylene glycol, ammonia) -15 μg .

Description:

Hard gelatin capsules:

No. 2, the case of a light orange color with the inscription "62", the lid of a light orange color with the inscription "H" (for a dosage of 30 mg);

No. 1, the body is dark orange with the inscription "61", the lid is a dark orange color with the inscription "H" (for a dosage of 40 mg).

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 (2'3'-didehydro-3'-deoxythymidine) is a synthetic one. analogue of thymidine nucleoside, suppresses replication of HIV 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 3'-hydroxyl groups in the molecule necessary for constructing DNA. In addition, stavudine triphosphate inhibits cellular DNA polymerases P and y and significantly reduces the synthesis of mitochondrial DNA.

Pharmacokinetics:

Adults. Stavudine quickly absorbed when taken orally. Absolute bioavailability is about 86.4%. After a single dose, the maximum concentration (Cmax) of the drug in the blood plasma is observed in less than 1 hour. Values of Cmax increase in proportion to the increase in doses of the drug. Stavudine cumulation at its application 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.

Apparent volume of distribution after a single dose of the drug is an average of 66 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 for 4-5 hours.The ratio of CSF to plasma concentration is about 40%.

After oral administration, the half-life (T%) of the drug is 1.44 hours and is dose independent. 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%. Pharmacokinetics after a single dose of the drug is similar to the pharmacokinetics in adults and does not depend on the dose. Drug concentration in CSF after single and repeated oral administration comprise from 16 to 125% relative to concentration in plasma. Cumulation of stavudine when taking 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. It is recommended to correct the dosage regimen.

Indications:

HIV infection (as part of combination therapy).

Contraindications:

Hypersensitivity to stavudine and / or any of the components of the drug, children weighing less than 30 kg,chronic renal failure (CRF) with creatinine clearance less than 50 ml / min. Lactase deficiency, lactose intolerance, glucose galactose malabsorption.

Carefully:

Alcoholism, chronic renal failure (creatinine clearance more than 50 ml / min), hepatic insufficiency, peripheral neuropathy, incl. in the anamnesis, a pancreatitis, a simultaneous reception with didanosine.

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, regardless of food intake. 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
> 30 and <60 kg	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 depending on the creatinine clearance:

Clearance of 'creatinine (ml / min)	Dose according to body weight
	>60 kg	. > 30 and <60 kg., -
> 50*-	, 40 mg every 12 hours	30 mg every 12 hours
* Usual dose, dose adjustment is not required

Children with impaired renal function. Precise recommendations for correcting 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:

From the central and peripheral nervous system: headache, insomnia, dizziness, asthenic syndrome; dose-dependent peripheral neuropathies (in 19-24% of adults): bilateral symmetrical sense of numbness of the limbs, tingling, pain in the feet, hands.

From the digestive system: pancreatitis (1%) of varying severity, including fatal cases; steatosis with hepatomegaly; hepatitis, dry mouth, decreased appetite, diarrhea, increased activity of "liver" transaminases, hyperbilirubinemia.

From the endocrine system and metabolism: lactic acidosis of varying severity, including cases with fatal outcome. Symptoms: nausea, vomiting, pain in the abdominal region, dyspnea, tachypnea, muscle weakness.

From the side of blood and blood-forming organs: anemia, neutropenia, thrombocytopenia

From the musculoskeletal system: arthralgia, myalgia.

Allergic reactions: skin rash, fever.

Other: chills, fat tissue redistribution, immunity reactivation syndrome.

Overdose:

Symptoms: peripheral neuropathy and 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 into an active metabolite is reduced, 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 medication,causing 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 with 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 (up to half the recommended dose). 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. When symptoms of pancreatitis appear, drug treatment should be discontinued. With the repeated administration of the drug to exclude the simultaneous use of didanosine and hydroxycarbamide. 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.

When the drug is used, the biochemical parameters of liver function may increase.

Lactic Acidosis¹ and the severe form of hepatic steatosis with hepatomegaly, including fatal cases, "are noted with the use of nucleoside analogs in combination with other antiretroviral drugs." "When d4T is used in combination with didanosine, the risk of liver dysfunction significantly increases." More often in women. the redistribution of adipose tissue - atrophy of subcutaneous fat on the face (around the eyes, on the temples), limbs and buttocks, excess visceral fat, also on the neck and the occiput e,in muscles and liver, the increase in mammary glands - is observed in the first months of therapy. 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.

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.

Effect on the ability to drive transp. cf. and fur:

During the use of the drug, patients should be very careful to drive and engage in other potentially hazardous activities, due to possible side effects from the nervous system, such as dizziness and numbness of the limbs

Form release / dosage:

Capsules of 30 mg and 40 mg.

When manufacturing on Hetero Labs Limited, India

10 capsules in a blister of a polyvinylchloride film and aluminum foil.

60 capsules in a can of polymeric, sealed aluminum foil, with a screw cap that has a device that prevents children from opening the can. Free space in the bank is filled with cotton hygroscopic cotton.A granular silica gel embedded in a paper sachet or a polyethylene container 6 listers or 1 bank together with instructions for use in the pack from cardboard.

When manufactured at LLC "MAKIZ-PHARMA"

7, 10 or 14 capsules in the contour cell pack of film polyvinylchloride and foil aluminum. 4 contour cell packs of 14 capsules, 8 contour cell packs of 7 capsules, 5 or 6 contour cell packs of 10 capsules together with the application in a pack of cardboard.

Packaging:

When manufacturing on Hetero Labs Limited, India

10 capsules in a blister of a polyvinylchloride film and aluminum foil.

60 capsules in a can of polymeric, sealed aluminum foil, with a screw cap that has a device that prevents children from opening the can. Free space in the bank is filled with cotton hygroscopic cotton. A granular silica gel embedded in a paper sachet or a polyethylene container 6 listers or 1 bank together with instructions for use in the pack from cardboard.

When manufactured at LLC "MAKIZ-PHARMA"

Storage conditions:

In a dry, protected from light 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 expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001125

Date of registration:09.03.2011

The owner of the registration certificate:DIALOGPARMA, LLC DIALOGPARMA, LLC Russia

Manufacturer: & nbsp

HETERO LABS, Limited India

MAKIZ-PHARMA, LLC Russia

Representation: & nbspDIALOGPARMA, LLCDIALOGPARMA, LLC

Information update date: & nbsp19.08.2015

Illustrated instructions

Instructions

Stag (Stag)