zidovudine

zidovudine

zye-doe-vue-deen

Trade Name(s): (Retrovir)

■BLACK BOX ALERT■ Neutropenia, severe anemia may occur. Lactic acidosis, severe hepatomegaly with steatosis (fatty liver), including fatalities, have occurred. Symptomatic myopathy, myositis associated with prolonged use.

Do not confuse Retrovir with acyclovir or ritonavir.

FIXED-COMBINATION(S)

Combivir: zidovudine/lamiVUDine (an antiviral): 300 mg/150 mg. Trizivir: zidovudine/lamiVUDine/abacavir (an antiviral): 300 mg/150 mg/300 mg.

Classification ⬆ ⬇

PHARMACOTHERAPEUTIC:Nucleoside reverse transcriptase inhibitors. CLINICAL:Antiretroviral.

Uses ⬆ ⬇

Treatment of HIV infection in combination with at least two other antiretroviral agents. Prevention of maternal/fetal HIV transmission. OFF-LABEL: Prophylaxis in health care workers at risk for acquiring HIV after occupational exposure (part of multidrug regimen).

Precautions ⬆ ⬇

Contraindications: Potentially life-threatening allergic reactions to zidovudine or its components. Cautions: Bone marrow compromise, renal/hepatic impairment. Combination with interferon with or without ribavirin in HIV/hepatitis C virus (HCV) coinfection.

Action ⬆ ⬇

Interferes with viral RNA-dependent DNA polymerase, an enzyme necessary for viral HIV replication. Therapeutic Effect: Slows HIV replication, reducing progression of HIV infection.

Pharmacokinetics ⬆ ⬇

Widely distributed. Protein binding: 25%-38%. Metabolized in liver. Crosses blood-brain barrier and is widely distributed, including to CSF. Primarily excreted in urine. Half-life: 0.5–3 hrs (increased in renal impairment).

Lifespan Considerations ⬆ ⬇

Pregnancy/Lactation: Unknown if drug crosses placenta or is distributed in breast milk. Unknown if fetal harm or effects on fertility can occur. Children: No age-related precautions noted. Elderly: Information not available.

Interactions ⬆ ⬇

DRUG: May decrease therapeutic effect of cladribine, DOXOrubicin, ganciclovir, interferons, valganciclovir. HERBAL: None significant. FOOD: None known. LAB VALUES: May increase mean corpuscular volume (MCV).

Availability ⬆ ⬇

Capsules: 100 mg. Injection Solution: (Retrovir): 10 mg/mL. Syrup: 50 mg/5 mL. Tablets: 300 mg.

Administration/Handling ⬆ ⬇

Reconstitution

Dilute in D5W to a final concentration no greater than 4 mg/mL.

Rate of administration

Infuse over 1 hr. May infuse over 30 min in neonates.

Storage

Refrigerate diluted solution for up to 24 hrs or store at room temperature for up to 8 hrs.
Do not use if solution is discolored or precipitate forms.

Give wilhout regard to food.
Space doses evenly around the clock.
Pt should maintain an upright position when given medication to prevent esophageal ulceration.

Indications/Routes/Dosage ⬆ ⬇

HIV Infection

PO: ADULTS, ELDERLY: 300 mg q12h. CHILDREN 4 WKS TO 18 YRS WEIGHING 30 KG OR MORE: 300 mg q12h. WEIGHING 9–29 KG: 9 mg/kg q12h. WEIGHING 4–8 KG: 12 mg/kg q12h. PREMATURE NEONATES, GA 35 WKS OR MORE: 4 mg/kg q12h, increase to 12 mg/kg q12h after 4 wks of age. GA 30–34 WKS: 2 mg/kg q12h for 2 wks, then 3 mg/kg q12h, then 12 mg/kg q12h after 6–8 wks. GA LESS THAN 30 WKS: 2 mg/kg q12h, then 3 mg/kg q12h at 4 wks of age, then 12 mg/kg q12h after 8–10 wks of age.

IV: adults, elderly, children older than 12 yrs: 1 mg/kg/dose q4h around the clock. children 12 yrs and younger, full-term neonates: 3 mg/kg/dose q12h. older than 4 wks: Increase to 9 mg/kg/dose q12h. premature neonates: 1.5–2.3 mg/kg/dose q12h based on gestation at birth. 6–10 wks: Increase to 9 mg/kg/dose q12h.

Prevention of Maternal/Fetal HIV Transmission

Note: Should be given IV near delivery regardless of antepartum regimen or mode of delivery in women with HIV RNA level greater than 1,000 copies/mL (or unknown status). Other antiretrovirals should be continued orally. Zidovudine IV is not required in pts receiving HIV therapy with HIV RNA level less than 1,000 copies/mL near delivery.

IV: DURING LABOR AND DELIVERY: 2 mg/kg loading dose, then IV infusion of 1 mg/kg/hr until delivery. For scheduled cesarean section, begin IV zidovudine 3 hrs before surgery. NEONATAL: Begin 6–12 hrs after birth and continue for first 6 wks of life. Use IV route only until oral therapy can be administered.

PO: FULL-TERM INFANTS: 4 mg/kg/dose q12h (IV: 3 mg/kg/dose q12h). INFANTS 30–34 WKS' GESTATION: 2 mg/kg/dose q12h; increase to 3 mg/kg/dose at 2 wks of age (IV: 1.5 mg/kg/dose q12h; increase to 2.3 mg/kg/dose q12h at 2 wks of age). INFANTS LESS THAN 30 WKS' GESTATION: 2 mg/kg/dose q12h. (IV: 1.5 mg/kg/dose q12h.)

Dosage in Renal Impairment

adults, elderly: CrCl less than 15 mL/min, including hemodialysis or peritoneal dialysis: PO: 100 mg q8h or 300 mg once daily. IV: 1 mg/kg q6–8hr. infants older than 6 wks, children, adolescents: GFR 10 mL/min/1.73m² or greater: No adjustment. GFR less than 10 mL/min/1.73m²: Administer 50% of dose q8h.

Dosage in Hepatic Impairment

No dose adjustment.

Side Effects ⬆ ⬇

Expected (46%-42%): Nausea, headache. Frequent (20%-16%): Abdominal pain, asthenia, rash, fever, acne. Occasional (12%—8%): Diarrhea, anorexia, malaise, myalgia, drowsiness. Rare (6%—5%): Dizziness, paresthesia, vomiting, insomnia, dyspnea, altered taste.

Adverse Effects/Toxic Reactions ⬆ ⬇

Anemia (occurring most commonly after 4–6 wks of therapy), granulocytopenia may occur in pts with pretherapy low baselines. Neurotoxicity (ataxia, fatigue, lethargy, nystagmus, seizures) may occur.

Nursing Considerations ⬆ ⬇

BASELINE ASSESSMENTObtain CBC, CD4 cell count, HIV RNA level, viral load. Obtain specimens for viral diagnostic tests before starting therapy (therapy may begin before results are obtained).INTERVENTION/EVALUATIONMonitor CBC, CD4 cell count, HIV RNA levels. Monitor for bleeding. Assess for headache, dizziness. Monitor daily pattern of bowel activity, stool consistency. Evaluate skin for acne, rash. Monitor for opportunistic infections (fever, chills, cough, myalgia). Monitor I&O, serum renal function, LFT.PATIENT/FAMILY TEACHING
Treatment is not a cure for HIV infection, nor does it reduce risk of transmission to others.
Do not take any medications without physician's approval.
Bleeding from gums, nose, rectum may occur and should be reported to physician immediately.
Dental work should be done before therapy or after blood counts return to normal (often wks after therapy has stopped).
Inform physician if muscle weakness, difficulty breathing, headache, inability to sleep, unusual bleeding, rash, signs of infection occur.

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Information ⬇