Azidotimidin (Capsules) Instructions for Use

Marketing Authorization Holder

Biopharma, CJS (Russia)

ATC Code

J05AF01 (Zidovudine)

Active Substance

Zidovudine (Rec.INN WHO registered)

Dosage Form

Azidotimidin

Capsules 100 mg: 100 or 200 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blister packs (10) – cardboard packs.
100 pcs. – dark glass jars (1) – cardboard packs.
100 pcs. – plastic bottles (1) – cardboard packs.
200 pcs. – dark glass jars (1) – cardboard packs.
200 pcs. – plastic bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug active against HIV

Pharmacotherapeutic Group

Antiviral [HIV] agent

Pharmacological Action

Antiviral agent, nucleoside reverse transcriptase inhibitor, thymidine analogue. Active against HIV.

After penetration into the cell, Zidovudine is sequentially metabolized to zidovudine triphosphate, which competes with the natural substrate thymidine triphosphate for incorporation into the chains of viral RNA-dependent DNA polymerase (reverse transcriptase), thereby suppressing the replication and growth of viral DNA.

The ability of zidovudine to inhibit HIV reverse transcriptase is 100-300 times higher than its ability to suppress human DNA polymerase.

Pharmacokinetics

After oral administration, it is rapidly and almost completely absorbed from the gastrointestinal tract. Penetrates the blood-brain barrier and the placental barrier. Plasma protein binding is 30-38%. Metabolized in the liver.

T_1/2 after oral and intravenous administration is 1 hour. Excreted in the urine: 14-18% unchanged, 60-74% as metabolites.

Indications

HIV infection (in adults and children over 3 months): primary manifestations (stage 2B, 2V according to the V.I. Pokrovsky classification) with a decrease in CD4 lymphocyte count below 400-500/µl, incubation stage (stage 1), stage of secondary diseases (3A, 3B, 3C), stage of acute infection (2A), children without symptoms of the disease but with a significant decrease in immune status.

Prevention of occupational infection in persons who have received needle sticks and cuts while working with HIV-contaminated material, and prevention of transplacental HIV infection of the fetus.

ICD codes

Dosage Regimen

It is set individually and depends on the stage of the disease, the degree of preservation of bone marrow reserves, the patient’s body weight, and the response to treatment.

For oral administration to adults – 500-600 mg/day, frequency of administration – 2-5 times/day; for children aged from 3 months to 12 years – 360-720 mg/m²/day in 4 divided doses.

Intravenous for adults – 1-2 mg/kg every 4 hours; for children – 120 mg/m² every 6 hours.

Adverse Reactions

From the hematopoietic system myelosuppression, anemia, neutropenia, leukopenia, lymphadenopathy, thrombocytopenia, pancytopenia with bone marrow hypoplasia, aplastic or hemolytic anemia.

From the digestive system nausea, vomiting, dyspepsia, dysphagia, anorexia, taste perversion, abdominal pain, diarrhea, flatulence, abdominal distension, pigmentation or ulceration of the oral mucosa, hepatitis, hepatomegaly with steatosis, jaundice, hyperbilirubinemia, increased activity of liver enzymes, pancreatitis, increased serum amylase activity.

From the nervous system headache, dizziness, paresthesia, insomnia, drowsiness, weakness, lethargy, decreased mental performance, tremor, convulsions; anxiety, depression, confusion, mania.

From the sensory organs macular edema, amblyopia, photophobia, vertigo, hearing loss.

From the respiratory system dyspnea, cough, rhinitis, sinusitis.

From the cardiovascular system cardiomyopathy, syncope.

From the urinary system frequent or difficult urination, hypercreatininemia.

From the endocrine system and metabolism lactic acidosis, gynecomastia.

From the musculoskeletal system: myalgia, myopathy, muscle spasm, myositis, rhabdomyolysis, increased activity of CPK, LDH.

Dermatological reactions pigmentation of nails and skin, increased sweating, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Allergic reactions skin rash, itching, urticaria, angioedema, vasculitis, anaphylactic reactions.

Other malaise, back and chest pain, fever, flu-like syndrome, pain syndrome of various localization, chills, development of secondary infection, redistribution of adipose tissue.

Contraindications

Neutropenia (neutrophil count less than 750/µl), hemoglobin level below 7.5 g/dl, hypersensitivity to zidovudine, concurrent use with stavudine, doxorubicin, other drugs that reduce the antiviral activity of zidovudine.

Use in Pregnancy and Lactation

It has been established that Zidovudine penetrates the placental barrier.

It is not known whether Zidovudine is excreted in breast milk, so if it is necessary to use during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Use with particular caution in hepatic insufficiency – adjustment of the dosage regimen is recommended depending on the dynamics of zidovudine concentration in the blood.

Use in Renal Impairment

Use with particular caution in renal insufficiency – adjustment of the dosage regimen is recommended depending on the dynamics of zidovudine concentration in the blood.

Geriatric Use

Use with particular caution in elderly patients – adjustment of the dosage regimen is recommended depending on the dynamics of zidovudine concentration in the blood.

Special Precautions

Use with particular caution in renal and hepatic insufficiency, as well as in elderly patients; in these cases, adjustment of the dosage regimen is recommended depending on the dynamics of zidovudine concentration in the blood.

During treatment, it is necessary to systematically conduct studies of liver function and peripheral blood (during the first 3 months of treatment – every 2 weeks; then at least once a month). Treatment should be discontinued if the hemoglobin level is less than 7.5 g/dl and/or the neutrophil count is less than 750/µl. After restoration of these parameters (usually after a 2-week break), treatment can be resumed.

Treatment should be interrupted in case of increasing hepatomegaly, rapid increase in liver transaminase activity, and development of lactic acidosis.

Drug Interactions

Drugs metabolized in the liver by conjugation with glucuronic acid (paracetamol, acetylsalicylic acid, indomethacin, ketoprofen, codeine, morphine, oxazepam, lorazepam, cimetidine, sulfonamides) may theoretically compete with zidovudine for metabolism and reduce its clearance. Therefore, with simultaneous use, the risk of developing the toxic effect of zidovudine or drugs interacting with it increases.

With simultaneous use with dapsone, pentamidine, amphotericin, flucytosine, ganciclovir, interferon, vincristine, vinblastine, doxorubicin, the risk of developing toxic effects increases.

With simultaneous use with ribavirin, antagonism regarding the antiviral effect has been established.

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.