zidovudine

zye-DOE-vue-deen

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: nucleoside reverse transcriptase inhibitors

REMS

HIV infection (in combination with other antiretrovirals).
Reduction of maternal/fetal transmission of HIV.

Unlabeled Use:

Chemoprophylaxis after occupational exposure to HIV.

Following intracellular conversion to its active form, inhibits viral RNA synthesis by inhibiting the enzyme DNA polymerase (reverse transcriptase).
Prevents viral replication.

Therapeutic effects:

Virustatic action against selected retroviruses.
Slowed progression and decreased sequelae of HIV infection.
Decreased viral load and improved CD4 cell counts.
Decreased transmission of HIV to infants born to HIV-infected mothers.

Absorption: Well absorbed following oral administration.

Distribution: Widely distributed; enters the CNS.

Metabolism/Excretion: Mostly (75%) metabolized by the liver; 15–20% excreted unchanged by the kidneys.

Half-Life: 1 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	0.5–1.5 hr	4 hr
IV	rapid	end of infusion	4 hr

Contraindicated in:

Hypersensitivity;
Lactation: Breastfeeding not recommended in mothers with HIV.

Use Cautiously in:

↓bone marrow reserve (dose ↓ required for anemia or granulocytopenia);
Women and obese patients (↑ risk of lactic acidosis and severe hepatomegaly);
Severe renal impairment;
Severe hepatic impairment;
Latex allergy (IV only);
Geri: Select dose carefully due to potential for age-related in hepatic, renal, or cardiac function in older adults.

Derm: nail pigmentation

Endo: gynecomastia

F and E: LACTIC ACIDOSIS

GI: abdominal pain, diarrhea, nausea, anorexia, dyspepsia, HEPATOMEGALY (WITH STEATOSIS), oral mucosa pigmentation, PANCREATITIS, vomiting

Hemat: anemia, granulocytopenia, pure red-cell aplasia, thrombocytosis

Metab: lipoatrophy

MS: back pain, myopathy

Neuro: headache, weakness, ↓mental acuity, anxiety, confusion, depression, dizziness, insomnia, restlessness, SEIZURES, syncope, tremor

Misc: immune reconstitution syndrome

Drug-drug:

↑bone marrow depression with other agents having bone marrow–depressing properties, antineoplastics, radiation therapy, or ganciclovir.
↑neurotoxicity may occur with acyclovir.
Toxicity may be ↑ by concurrent administration of probenecid or fluconazole.
Levels are ↓ by clarithromycin.

HIV Infection

PO (Adults ): 100 mg every 4 hr while awake or 200 mg 3 times daily or 300 mg twice daily (depends on combination and clinical situation).
PO (Children 4 wk–<18 yr): 4–8.9 kg: 12 mg/kg twice daily or 8 mg/kg 3 times daily; 9–29.9 kg: 9 mg/kg twice daily or 6 mg/kg 3 times daily; ≥30 kg: 300 mg twice daily or 200 mg 3 times daily.
IV (Adults and Children >12 yr): 1 mg/kg every 4 hr. Change to oral therapy as soon as possible.
IV (Children ): 120 mg/m² every 6 hr (not to exceed 160 mg/dose) or 20 mg/m²/hr as a continuous infusion.

Prevention of Maternal/Fetal Transmission of HIV Infection

PO (Adults >14 wk Pregnant): 100 mg 5 times daily until onset of labor.
IV (Adults during Labor and Delivery): 2 mg/kg over 1 hr, then continuous infusion of 1 mg/kg/hr until umbilical cord is clamped.
PO (Neonates ): 2 mg/kg every 6 hr until 6 wk of age.
IV (Neonates ): 1.5 mg/kg every 6 hr until 6 wk of age.

(Generic available)

Tablets: 300 mg
Capsules: 100 mg
Oral solution: 50 mg/5 mL
Solution for injection: 10 mg/mL
In combination with: lamivudine (Combivir); abacavir and lamivudine; see Appendix [not included in this PDA edition].

Assess patient for change in severity of symptoms of HIV and for symptoms of opportunistic infections during therapy.

Lab Test Considerations:

Monitor viral load and CD4 counts prior to and periodically during therapy.
- Monitor CBC every 2 wk during the first 8 wk of therapy in patients with advanced HIV disease, and decrease to every 4 wk after the first 2 mo if zidovudine is well tolerated or monthly during the first 3 mo and every 3 mo thereafter unless indicated in patients who are asymptomatic or have early symptoms. Commonly causes granulocytopenia and anemia. Anemia may occur 2–4 wk after initiation of therapy. Anemia may respond to epoetin administration (see epoetin monograph). Granulocytopenia usually occurs after 6–8 wk of therapy. Consider dose reduction, discontinuation of therapy, or blood transfusions if hemoglobin <7.5 g/dL or reduction of >25% from baseline and/or granulocyte count <750/mm³ or reduction of >50% from baseline. Therapy may be gradually resumed when bone marrow recovery is evident.
- May cause ↑ serum AST, ALT, and alkaline phosphatase levels.Lactic acidosis may occur with hepatic toxicity, causing hepatic steatosis; may be fatal, especially in women.
- Monitor serum amylase, lipase, and triglycerides periodically during therapy. Elevated serum levels may indicate pancreatitis and require discontinuation.

Do not confuse Retrovir (zidovudine) with ritonavir.
PO: Administer doses around the clock.
- For neonates, use a syringe with 0.1-mL graduations to ensure accurate dosing of the oral solution.
IV: Patient should receive the IV infusion only until oral therapy can be administered.

IV Administration:

Intermittent Infusion: Retrovir vial stoppers contain latex; may cause allergic reactions in latex-sensitive individuals. Diluent: Remove calculated dose from the vial and dilute with D5W or 0.9% NaCl. Do not use solutions that are discolored. Stable for 24 hr at room temperature or 48 hr if refrigerated.Concentration: Not to exceed 4 mg/mL.
Rate: Infuse at a constant rate over 1 hr in adults or over 30 min in neonates. Avoid rapid infusion or bolus injection.
Has also been administered via continuous infusion.

Instruct patient to take zidovudine as directed, around the clock, even if sleep is interrupted. Emphasize the importance of compliance with therapy, not taking more than prescribed amount, and not discontinuing without consulting health care professional. Take missed doses as soon as remembered unless almost time for next dose; do not double doses. Inform patient that long-term effects of zidovudine are unknown at this time.
Instruct patient that zidovudine should not be shared with others.
Zidovudine may cause dizziness or fainting. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Inform patient that zidovudine does not cure HIV and may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom during sexual contact and avoid sharing needles or donating blood to prevent spreading the AIDS virus to others.
Instruct patient to notify health care professional promptly if signs of pancreatitis (nausea, vomiting, abdominal pain), lactic acidosis (feel very weak or tired; feel cold, especially in arms and legs; unusual muscle pain; feel dizzy or lightheaded; trouble breathing; fast or irregular heartbeat; stomach pain with nausea and vomiting), liver problems (yellowing of skin or white part of eyes; loss of appetite; nausea; dark or "tea-colored" urine; pain, aching, or tenderness on right side of abdomen; light-colored stools) or immune reconstitution syndrome (signs and symptoms of an infection,
Mycobacterium avium
infection, cytomegalovirus,
Pneumocystis jirovecii
pneumonia, tuberculosis) occur.
Instruct patient to notify health care professional promptly if fever, sore throat, signs of infection, muscle weakness, or shortness of breath occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush, to use caution when using toothpicks or dental floss, and to have dental work done prior to therapy or deferred until blood counts return to normal.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and avoid breastfeeding. Advise patient taking oral contraceptives to use a nonhormonal method of birth control during therapy. Inform patient of pregnancy exposure registry that monitors pregnancy outcomes in women exposed to zidovudine during pregnancy. Enroll patients in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

Decrease in viral load and increase in CD4 counts in patients with HIV.
Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
Reduction of maternal/fetal transmission of HIV.

Retrovir

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆