zidovudine (azidothymidine, AZT, Compound S)

zidovudine (azidothymidine, AZT, Compound S)

(zid o vew' den)

Aztec, Retrovir

Pregnancy Category C

Drug class

Antiviral

Therapeutic actions

Thymidine analogue isolated from the sperm of herring; drug is activated to a triphosphate form that inhibits replication of some retroviruses, including HIV, HTLV III, lymphadenopathy-associated virus, ARV.

Indications

·        Management of certain adult patients with symptomatic HIV infection in combination with other antiretrovirals

·        Prevention of maternal–fetal HIV transmission

Contraindications and cautions

·        Contraindicated with life-threatening allergy to any component, pregnancy, lactation.

·        Use cautiously with compromised bone marrow, impaired renal or hepatic function.

Available forms

Capsules—100 mg; tablets—300 mg; CR tablets—30 mg; syrup—50 mg/5 mL; injection—10 mg/mL

Dosages

ADULTS

Oral

·        Symptomatic HIV infection: Initially, 100 mg q 4 hr (2.9 mg/kg q 4 hr) PO, around-the-clock, or 600 mg daily in divided doses as either 200 mg tid or 300 mg bid. Monitor hematologic indices every 2 wk. If significant anemia (Hgb < 7.5 g/dL, reduction of > 25%) or reduction of granulocytes > 50% below baseline occurs, dose interruption is necessary until evidence of bone marrow recovery is seen. If less severe bone marrow depression occurs, a dosage reduction may be adequate; or 1–2 mg/kg q 4 hr IV.

·        Asymptomatic HIV infection: 100 mg q 4 hr PO while awake (500 mg/day).

·        Maternal–fetal transmission: 100 mg PO five times/day from 14 wk gestation to the start of labor.

IV

1–2 mg/kg q 4 hr infused over 1 hr.

PEDIATRIC PATIENTS

6 wk–12 yr: 160 mg/m² q 8 hr; 90–180 mg/m² q 6–8 hr, not to exceed 200 mg per dose q 8 hr).

Infants born to HIV-infected mothers: 2 mg/kg q 6 hr starting within 12 hr of birth to 6 wk of age or 1.5 mg/kg IV over 30 min q 6 hr.

Pharmacokinetics

Route	Onset	Peak
Oral	Varies	30–90 min
IV	Rapid	End of infusion

Metabolism: Hepatic; T_1/2: 30–60 min

Distribution: Crosses placenta; may enter breast milk

Excretion: Urine

IV facts

Preparation: Remove desired dose from vial, and dilute in 5% dextrose in water to a concentration no greater than 4 mg/mL. Discard after 24 hr. Protect from light.

Infusion: Administer over 60 min; avoid rapid infusion. For a pregnant patient, when labor starts, given to the mother as a single 2 mg/kg dose infused over 1 hr followed by 1 mg/kg/hr given by continuous IV infusion until the umbilical cord is clamped.

Incompatibilities: Do not mix with blood or blood products.

Adverse effects

·        CNS: Headache, insomnia, myalgia, asthenia, malaise, dizziness, paresthesias, somnolence

·        GI: Nausea, GI pain, diarrhea, anorexia, vomiting, dyspepsia

·        Hematologic: Agranulocytopenia, severe anemia requiring transfusions

·        Other: Fever, diaphoresis, dyspnea, rash, taste perversion

Interactions

Drug-drug

·        Increased risk of hematologic toxicity if combined with nephrotoxic, cytotoxic, or bone marrow suppressing drugs, ganciclovir, interferon alfa

·        Increased risk of neurotoxicity when used with acyclovir

·        Severe drowsiness and lethargy with cyclosporine

Drug-alternative therapy

·        Decreased effectiveness if taken with St. John’s wort

Nursing considerations

CLINICAL ALERT!

Name confusion has been reported between ritonavir and Retrovir (zidovudine); use caution.

Assessment

·        History: Life-threatening allergy to any component; compromised bone marrow; impaired renal or hepatic function; pregnancy, lactation

·        Physical: Skin rashes, lesions, texture; T; affect, reflexes, peripheral sensation; bowel sounds, liver evaluation; LFTs, renal function tests, CBC and differential

Interventions

·        Monitor hematologic indices every 2 wk.

·        Give the drug around-the-clock; rest periods may be needed during the day due to interrupted sleep.

Teaching points

·        Take drug every 4 hours, around-the-clock. Use an alarm clock to wake you up at night; rest periods during the day may be needed. Do not share this drug; take exactly as prescribed.

·        Zidovudine is not a cure for AIDS or AIDS-related complex; opportunistic infections may occur; obtain continuous medical care.

·        Arrange for frequent blood tests; results of blood counts may indicate dosage needs to be decreased or drug discontinued temporarily.

·        Zidovudine does not reduce the risk of transmission of HIV to others by sexual contact or blood contamination; use precautions.

·        You may experience these side effects: Nausea, loss of appetite, change in taste (eat frequent small meals); dizziness, loss of feeling (use precautions); headache, fever, muscle aches.

·        Report extreme fatigue, lethargy, severe headache, severe nausea, vomiting, difficulty breathing, rash.

Adverse effects in Italic are most common; those in Bold are life-threatening.