Vero-Stavudine (Capsules) Instructions for Use

Marketing Authorization Holder

Veropharm, JSC (Russia)

ATC Code

J05AF04 (Stavudine)

Active Substance

Stavudine (Rec.INN registered by WHO)

Dosage Form

Vero-Stavudine

Capsules 30 mg: 28, 56, or 270 pcs.

Dosage Form, Packaging, and Composition

Capsules No. 1, white body, orange cap; capsule contents are a white or almost white powder.

Excipients: lactose monohydrate 187.6 mg, corn starch 64.55 mg, magnesium stearate 2.85 mg.

Capsule shell composition: iron oxide yellow, titanium dioxide, gelatin, sunset yellow FCF.

7 pcs. – blister packs (8) – cardboard boxes.
10 pcs. – blister packs (27) – cardboard boxes.
14 pcs. – blister packs (4) – cardboard boxes.
28 pcs. – polymer jars (1) – cardboard boxes.
56 pcs. – polymer jars (1) – cardboard boxes.

Clinical-Pharmacological Group

Antiviral drug active against HIV

Pharmacotherapeutic Group

Antiviral [HIV] agent

Pharmacological Action

Antiviral agent, a synthetic analogue of thymidine. Active against HIV. It is metabolized in cells to stavudine triphosphate, which, by inhibiting HIV reverse transcriptase, disrupts the process of viral DNA elongation.

In addition, stavudine triphosphate inhibits cellular DNA polymerases, significantly suppressing the synthesis of mitochondrial DNA.

Pharmacokinetics

Rapidly absorbed from the gastrointestinal tract. Bioavailability is 78-86%. C_max is reached within 0.5-1.5 hours. Penetrates the blood-brain barrier. V_d is 0.8-1.1 l/kg.

Metabolized by phosphorylation to form the active metabolite, stavudine triphosphate. 40% of stavudine is excreted unchanged in the urine. T_1/2 is 1-1.6 hours.

Indications

Treatment of HIV infection as part of combination therapy when other antiretroviral drugs cannot be used.

The duration of therapy with stavudine should be limited to the shortest possible time.

ICD codes

Dosage Regimen

The duration of therapy with stavudine must be limited to the shortest possible time.

Administer orally. Set the dose based on patient body weight.

For patients weighing 60 kg or more, the single dose is 40 mg.

For patients weighing less than 60 kg, the single dose is 30 mg.

Administer twice daily with an approximate 12-hour interval between doses.

In patients with renal impairment (CrCl >50 ml/min), reduce the dose according to creatinine clearance values.

Do not use in patients with severe renal impairment (CrCl <50 ml/min).

Use with caution in elderly patients due to increased risk of peripheral neuropathy and higher frequency of renal function impairment.

Adverse Reactions

Before starting therapy with stavudine, it is necessary to assess the expected benefit and possible risk of use for each patient and carefully consider the possibility of switching to an alternative treatment regimen.

Side effects have been observed with the use of various therapeutic regimens involving stavudine.

Stavudine+lamivudine+efavirenz

Endocrine system infrequently – gynecomastia; frequency unknown – diabetes mellitus, hyperglycemia.

Digestive system frequently – diarrhea, constipation, abdominal pain, nausea, dyspepsia, flatulence, dry mouth, increased appetite, gastritis; infrequently – vomiting, pancreatitis.

Liver and biliary tract: frequency unknown – hepatic steatosis, hepatitis, hepatic failure.

Metabolism frequently – lipoatrophy, lipodystrophy; infrequently – lactic acidosis (sometimes with muscle weakness), anorexia.

Musculoskeletal system infrequently – arthralgia, myalgia.

Nervous system frequently – depression, peripheral neuropathy, paresthesia, peripheral neuritis, dizziness, abnormal dreams, headache, insomnia, drowsiness, abnormal thoughts, anxiety, emotional lability.

Hematopoietic system frequency unknown – macrocytosis, anemia, neutropenia, thrombocytopenia.

Skin and subcutaneous tissue frequently – rash, itching; infrequently – urticaria.

Laboratory parameters: increased bilirubin concentration, increased AST, ALT, lipase activity.

General reactions frequently – feeling of tiredness; infrequently – asthenia.

Stavudine + lamivudine+indinavir

Digestive system very frequently – diarrhea, nausea, vomiting.

Nervous system very frequently – peripheral neuropathy, paresthesia, peripheral neuritis, headache.

Laboratory parameters: increased bilirubin concentration, increased AST, ALT, lipase activity.

Contraindications

Hypersensitivity to stavudine; simultaneous use with hydroxyurea, zidovudine, didanosine; pediatric age – depending on the dosage form; breastfeeding period.

With caution impaired liver function, incl. chronic hepatitis in the active stage; history of peripheral neuropathy, history of pancreatitis, concomitant use with doxorubicin and ribavirin; impaired renal function (CrCl > 50 ml/min).

Use in Pregnancy and Lactation

Adequate and well-controlled studies on the use of stavudine in pregnant women have not been conducted. Cases of lactic acidosis have been reported in pregnant patients receiving a combination of stavudine and didanosine with other antiretroviral drugs.

Stavudine as part of combination therapy during pregnancy should be used only in case of extreme necessity, justified by the clinical situation. Patients taking Stavudine during pregnancy should be under close supervision due to the possible development of lactic acidosis/hepatic steatosis.

If it is necessary to use during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function, incl. with chronic hepatitis in the active stage.

Use in Renal Impairment

Contraindicated in patients with impaired renal function with CrCl < 50 ml/min. Should be used with caution in chronic renal failure (CrCl > 50 ml/min). The dose of stavudine should be reduced according to CrCl values.

Pediatric Use

Can be used in children of appropriate age/with appropriate body weight strictly according to indications, in recommended doses, regimens and dosage forms. It is necessary to strictly follow the instructions in the stavudine drug labels regarding contraindications for the use of specific stavudine dosage forms in children of different ages.

Geriatric Use

Should be used with caution in elderly patients due to an increased risk of developing peripheral neuropathy; in addition, this age group on average has a higher frequency of impaired renal function.

Special Precautions

Use with caution in patients with impaired liver function. During treatment with stavudine, it is necessary to monitor the activity of liver enzymes (ALT, AST, ALP), amylase and lipase in blood plasma.

Immune reconstitution syndrome has been observed in patients receiving combined antiretroviral therapy, including treatment with stavudine. In patients with severe immunodeficiency at the start of combined antiretroviral therapy, an inflammatory reaction to latent or residual resistant pathogens present in the body may develop, which can significantly worsen the patient’s general condition or intensify the symptoms of the disease. Patients should be carefully monitored to promptly identify any inflammatory diseases and treat them.

Effect on ability to drive vehicles and machinery

During the use of stavudine, patients should exercise caution when driving vehicles and machinery, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Simultaneous use with zidovudine has established antagonism in the manifestation of antiviral action.

Caution should be exercised when stavudine is used concomitantly with doxorubicin and ribavirin, as doxorubicin and ribavirin inhibit the phosphorylation of stavudine in vitro.

When used concomitantly with didanosine, serious and/or life-threatening adverse events may develop, in particular lactic acidosis, impaired liver function, pancreatitis, peripheral neuropathy.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.