zidovudine


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Related to zidovudine: stavudine, didanosine

zidovudine

 [zi-do´vu-dēn]
a nucleoside analogue to thymidine, used as an antiretroviral agent in treatment of patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS); administered orally or intravenously. It was the first agent approved for such use.

zidovudine

Apo-Zidovudine (CA), Novo-AZT (CA), Retrovir

Pharmacologic class: Nucleoside reverse transcriptase inhibitor

Therapeutic class: Antiretroviral

Pregnancy risk category C

FDA Box Warning

• Drug has been linked to hematologic toxicity (including neutropenia and severe anemia), particularly in patients with advanced human immunodeficiency virus (HIV) infection.

• Prolonged use is associated with symptomatic myopathy.

• Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have occurred with use of nucleoside analogs alone or in combination, including zidovudine and other antiretrovirals.

Action

After conversion to its active metabolite, inhibits activity of HIV reverse transcriptase and terminates viral DNA growth

Availability

Capsules: 100 mg

Injection: 10 mg/ml in 20-ml vial

Syrup: 50 mg/5 ml

Tablets: 300 mg

Indications and dosages

HIV-1 infection

Adults and children older than age 12: 600 mg P.O. total daily dosage divided into either b.i.d. or t.i.d. dosing; or 1 mg/kg I.V. five to six times daily; in combination with other antiretrovirals

Children ages 4 weeks to younger than 18 years weighing 30 kg (66 lb) or more: 600 mg P.O. total daily dosage divided into either b.i.d. or t.i.d. dosing; or 480 mg/m2 total daily dosage divided into either b.i.d. or t.i.d. dosing. Don't exceed recommended adult dosage.

Children ages 4 weeks to younger than 18 years weighing 9 kg (20 lb) to less than 30 kg (66 lb): 18 mg/kg/day total daily dosage divided into either b.i.d. or t.i.d. dosing; or 480 mg/m2 total daily dosage divided into either b.i.d. or t.i.d. dosing. Don't exceed recommended adult dosage.

Children ages 4 weeks to younger than 18 years weighing 4 kg (9 lb) to less than 9 kg (20 lb): 24 mg/kg/day total daily dosage divided into either b.i.d. or t.i.d. dosing; or 480 mg/m2 total daily dosage divided into either b.i.d. or t.i.d. dosing. Don't exceed recommended adult dosage.

To prevent maternal-fetal HIV transmission

Pregnant women (more than 14 weeks of pregnancy): 500 mg P.O. daily in divided doses (usually as five 100-mg doses) until labor begins; then 2 mg/kg I.V. over 1 hour followed by a continuous infusion of 1 mg/kg/hour until umbilical cord is clamped

Neonates: 2 mg/kg P.O. q 6 hours starting within 12 hours of delivery and continuing for 6 weeks. For neonates unable to receive oral dosing, 1.5 mg/kg by I.V. infusion over 30 minutes q 6 hours

Dosage adjustment

• End-stage renal disease in patients maintained on hemodialysis or peritoneal dialysis

• Hematologic toxicity

• Concurrent use of drugs (such as fluconazole or valproic acid) in patients experiencing pronounced anemia

Off-label uses

• Occupational exposure to HIV

Contraindications

• Patients who have had potentially life-threatening allergic reactions (such as anaphylaxis, Stevens-Johnson syndrome) to drug or its components

Precautions

Use cautiously in:

• renal or hepatic impairment, known risk factors for liver disease, decreased bone marrow reserve, hemoglobin less than 9.5 g/dl, granulocyte count less than 1,000 cells/mm3

• concurrent use of Combivir or Trizivir (zidovudine-containing products) or interferon- and ribavirin-based regimens

• pregnant or breastfeeding patients.

Administration

For I.V. use, remove dose from vial and add to I.V. solution containing dextrose 5% in water, to yield a final concentration no higher than 4 mg/ml. Infuse over 1 hour. Avoid rapid infusion or bolus injection. Don't give by I.M. route.

• In adults, give by I.V. route only until patient can tolerate oral dose.

• If a child is unable to reliably swallow a capsule or tablet, give syrup formulation.

Adverse reactions

CNS: headache, paresthesia, malaise, insomnia, dizziness, drowsiness, asthenia, seizures

GI: nausea, vomiting, constipation, abdominal pain, dyspepsia, anorexia, pancreatitis

Hematologic: severe anemia (necessitating transfusions), agranulocytopenia, severe bone marrow depression

Hepatic: severe hepatomegaly with steatosis

Metabolic: lactic acidosis

Musculoskeletal: myalgia, back pain, myopathy

Respiratory: dyspnea

Skin: diaphoresis, rash, altered nail pigmentation

Other: abnormal taste, fever, immune reconstitution syndrome

Interactions

Drug-drug. Acetaminophen, aspirin, indomethacin: increased risk of zidovudine toxicity

Amphotericin B, dapsone, flucytosine, pentamidine: increased risk of nephrotoxicity and bone marrow depression

Cyclosporine: extreme drowsiness, lethargy

Cytotoxic drugs, myelosuppressants, nephrotoxic drugs (such as ganciclovir, interferon alfa): increased risk of hematologic toxicity

Fluconazole, methadone, probenecid, valproic acid: increased zidovudine blood level, greater risk of toxicity

Ribavirin: antagonism of zidovudine's antiviral activity

Drug-diagnostic tests. Granulocytes, hemoglobin, platelets: decreased levels

Drug-herbs. St. John's wort: decreased zidovudine efficacy

Patient monitoring

• Monitor neurologic status, especially for signs and symptoms of impending seizure.

Periodically assess CBC and kidney and liver function tests. Be aware that drug can cause hepatotoxicity.

Watch for signs and symptoms of pancreatitis, immune reconstitution syndrome, and lactic acidosis.

Patient teaching

• Tell patient he may take with or without food.

• Instruct patient to take capsules with at least 4 oz of fluid and to stay upright after taking.

• Explain therapy to patient. Emphasize that drug doesn't cure HIV infection.

• Urge patient to take drug exactly as prescribed.

Teach patient to recognize and immediately report signs and symptoms of serious side effects, such as seizures.

• Stress importance of follow-up laboratory testing.

• Advise female of childbearing age to use effective contraception.

• Inform pregnant patient that drug reduces risk of, but may not prevent, HIV transmission to neonate.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.

zi·do·vu·dine

(zī-dō'vū-dēn),
A thymidine analog that is an inhibitor of in vitro replication of HIV virus, the causative agent of AIDS and ARC, and is used in the management of these diseases.
Synonym(s): azidothymidine

zidovudine

(zĭ-dō′vyo͞o-dēn′)
n. Abbr. ZDV
See AZT.

AZT

A nucleoside analogue used with other anti-HIV agents to manage AIDS and HIV infection.
 
Adverse effects
Long-term AZT use is associated with muscle loss, nausea, anaemia, myelosuppression, oral ulcers, bone marrow damage and headache.

zidovudine

AZT 3'-azido-3'-deoxythimidine AIDS A thymidine analogue and HIV-1 antimetabolite, which slows progression of AIDS and terminating HIV's DNA chain growth Indications AIDS and Pneumocystis carinii pneumonia, CD4+ T-helper cells < 200/mm3, zidovudine therapy–ZT ↓ vertical maternal-infant transmission of HIV, HIV-1 infected children with neurodevelopmental abnormalities Effect Improved sense of well-being, ↑ CD4+ T cells, ↓ AIDS-related complications Side effects Dose-limiting myelosuppression with granulocytopenia–which may respond to lithium, anemia, headache, insomnia, mania, seizures, nausea, myalgia, lymphoma. See AIDS therapy.

zi·do·vu·dine

(ZDV) (zī-dō'vyū-dēn)
A thymidine analogue that is an inhibitor of in vitro replication of HIV virus; also used in pharmacotherapeutic management of AIDS.

zidovudine

An antiviral drug used to try to retard the progress of AIDS. Also known as azidothymidine or AZT. The drug is on the WHO official list. A brand name is Retrovir.

zi·do·vu·dine

(ZDV) (zī-dō'vyū-dēn)
A thymidine analogue that is an inhibitor of in vitro replication of HIV virus; also used in pharmacotherapeutic management of AIDS.
References in periodicals archive ?
Keywords: Zidovudine, pigmentation, zidovudine-induced pigmentation, HIV.
Furthermore and more importantly, to be considered for the study, one must have been on any two of the commonly prescribed regimens, namely, tenofovir with lamivudine and efavirenz (tenofovir cohort) or zidovudine with lamivudine and efavirenz.
Among the 21 patients with Zidovudine induced anaemia, majority (13 patients) were females; majority of the patients (16 patients) developed anaemia within 6 months of starting Zidovudine based regimen and the mean duration of development of anaemia was 3.94 months.
Hansen et al., "The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection.
The transmission rate was 0.7% for women who had received HAART and had either a planned cesarean section or a planned vaginal delivery, and 0.0% for those treated with zidovudine monotherapy who had a planned cesarean; among untreated women, the transmission rate was 9%.
(12) The zidovudine uptake from April 2004 appeared steady, with little variation between the districts, although one might have expected a variation in the administration of zidovudine between rural and urban districts, and that women in rural areas might not have been adequately covered as the result of more limited access to antenatal services.
"Approval of this additional dosage form of zidovudine," he says, "should help reduce the cost of this therapy for American patients."
(2002) investigated the induction of mutations and micronuclei in mice treated neonatally (from days 1-8 of age) with zidovudine (AZT), lamivudine (3TC), or a combination of the two drugs.
* A paper in The New England Journal of Medicine reports that zidovudine (Retrovir) reduces rates of perinatal transmission, even when used as an abbreviated regimen that is begun intrapartum or in the first 48 hours of life.
The researchers administered two daily antiviral drugs, zidovudine and lamivudine.
Those products include Retrovir (zidovudine), Combivir (lamivudine/zidovudine), Epivir (lamivudine), Trizivir (abacavir, lamivudine, and zidovudine), Ziagen (abacavir), and Zofran (ondansetron), according to the company.
As trial coordinator, FHI collaborated with Makerere University in Kampala, Johns Hopkins University in Baltimore, MD, USA, the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle, WA, USA, and several other partners to test the safety and efficacy of the antiretroviral nevirapine versus a specific regimen of the antiretroviral zidovudine (AZT) for preventing transmission from more than 600 pregnant, HIV-infected women to their infants.