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|Zidovudine

Zidovudine

Trade Names:
Retrovir
- Tablets 300 mg
- Capsules 100 mg
- Syrup 50 mg/5 mL
- Injection 10 mg/mL

Mechanism of Action

Pharmacology

Inhibits replication of retroviruses including HIV.

Pharmacokinetics

Absorption

Rapidly absorbed, not affected by food. T _max is 0.5 to 1.5 hr. Oral bioavailability is 64%. AUC is equivalent whether it is tablets or capsules.

Distribution

It is extensively distributed. Binding to plasma protein is low, less than 38%. Apparent Vd is about 1.6 L/kg.

Metabolism

Hepatic metabolism. Major metabolites are D-glucopyranuronosylthymidine (GZDV) and 3′-amino-3′-deoxythymidine. GZDV AUC is about 3-fold greater than zidovudine.

Elimination

Primarily eliminated by hepatic metabolism. T _½ is 0.5 to 3 hr. GZDV (74%) and zidovudine (14%) are recovered in the urine.

Special Populations

Ccr is at least 15 mL/min. Dose adjustment is not necessary; however, Cl decreases resulting in an increased t _½ of drug and metabolite and increased AUC. A dose adjustment is necessary for patients undergoing hemodialysis or peritoneal dialysis.

Limited information; however, it is expected Cl would decrease and plasma concentration would increase.

Children older than 3 mo are similar to those in adults.

Mothers should not breast-feed their infants to avoid risking postnatal transmission of HIV.

Indications and Usage

In combination with other antiretroviral agents for the treatment of HIV infections; prevention of maternal-fetal HIV transmission.

Contraindications

Life-threatening hypersensitivity to any component.

Dosage and Administration

PO 600 mg/day in divided doses in combination with other antiretroviral agents.

PO Greater than 14 wk of pregnancy-100 mg orally 5 times/day until the start of labor. During labor and delivery, administer IV zidovudine at 2 mg/kg over 1 hr followed by a continuous IV infusion of 1 mg/kg/hr until clamping of the umbilical cord.

PO 2 mg/kg orally q 6 hr starting within 12 hr after birth and continuing through 6 wk of age. Infants unable to receive oral dosing may be given zidovudine IV at 1.5 mg/kg, infused over 30 min, q 6 hr.

General Advice

• Use syrup, tablet, or capsule form for oral administration according to patient needs. Do not interchange between syrup and capsules. Syrup form absorbs faster than capsule form.
• Dilute IV preparation prior to administration. Remove calculated dose from vial; add to 5% dextrose to achieve concentration of up to 4 mg/mL.
• Do not mix with biologic or colloidal fluids (eg, blood products, protein solutions).
• Infuse over 1 hr at constant rate. Avoid rapid infusion or bolus.

Storage/Stability

Store capsules at room temperature in a tight, light-resistant container. Protect from heat and moisture. Store syrup at room temperature. Protect from light. After dilution, the solution is physically and chemically stable for 24 hr at room temperature and 48 hr if refrigerated. As an additional precaution, administer the diluted solution within 8 hr if stored at room temperature or 24 hr if refrigerated to minimize the potential administration of a microbially contaminated solution. Store undiluted vials at room temperature and protect from light.

Drug Interactions

May decrease zidovudine serum concentrations, reducing the therapeutic effect.

Possible increased risk of neurotoxicity (lethargy or seizure).

May increase risk of toxicity, including nephrotoxicity, cytotoxicity, or hematologic toxicity.

May increase serum concentration and potential toxicity of zidovudine.

May antagonize the effect of zidovudine.

May affect RBC/WBC counts or function and may increase potential for hematologic toxicity.

Life-threatening hematologic toxicity may occur.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

ECG abnormality; vasodilation; syncope; cardiomyopathy; CHF.

CNS

Headache; dizziness; insomnia; paresthesia; malaise; asthenia; decreased reflexes; nervousness or irritability.

Dermatologic

Rash; acne.

EENT

Taste perversion; hearing loss.

GI

Anorexia; constipation; dyspepsia; nausea; vomiting; dysphagia; flatulence; bleeding of the gums; rectal hemorrhage; mouth ulcers; edema of the tongue; eructation; abdominal pain.

Hematologic

Anemia; granulocytopenia; pancytopenia.

Respiratory

Dyspnea; cough; epistaxis; pharyngitis; rhinitis; sinusitis; hoarseness.

Miscellaneous

Fever, diaphoresis; myalgia; arthralgia; muscle spasm; body odor; chills; edema of the lip; flu syndrome; hyperalgesia; abdominal/back/chest pain; hypersensitivity reaction; anemia, neutropenia (infants).

Precautions

Pregnancy

Category C .

Lactation

Undetermined. HIV-infected mothers should not breast-feed.

Children

Dosing regimen not established in children less than 3 mo.

Hypersensitivity

Sensitization reactions, including anaphylaxis, have occurred.

Renal Function

May have greater risk of toxicity.

Hepatic Function

May have greater risk of toxicity.

Hematologic effects

Use with extreme caution in patients with bone marrow compromise (Hgb less than 9.5 g/dL or granulocyte count less than 1000/mm ³ ).

Overdosage

Symptoms

Nausea, vomiting, fatigue, headache, hematologic changes.

Patient Information

• Advise patient to take exactly as prescribed.
• Advise patient not to share medication and not to exceed the recommended dose.
• Inform patient that fever, sore throat, shortness of breath, and dizziness require immediate attention by health care provider. These may be signs of severe anemia or decreased WBCs and may indicate need for blood transfusion.
• Explain that health care provider will request follow-up blood or urine studies; do not skip appointments.
• Tell patient to notify health care provider of headache, insomnia, nausea, muscle aches, dyspnea, numbness or tingling, nervousness, loss of appetite, diarrhea, GI pain, vomiting, rash, excessive sweating, swelling of feet and legs, and taste perversions.
• Explain that drug does not prevent transmission of disease.
• Caution patient not to take any other drugs without consulting health care provider. This especially includes acetaminophen (eg, Tylenol ), aspirin, indomethacin, and acyclovir.
• Instruct patient to increase fluid intake to 2 to 3 L/day.
• Advise patient to record weight daily.
• Tell patient to protect medication from light during storage.
• Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
• Explain that long-term effects of drug are not known at this time.
• Advise patient that zidovudine therapy has not been shown to reduce the risk of transmission of HIV to others through sexual contact or blood contamination.
• Advise pregnant women considering use of the drug to prevent maternal-fetal transmission of HIV that transmission may still occur in some cases despite therapy. Long-term consequences of in utero and infant exposure are unknown.