zidovudine

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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

/zi·do·vu·dine/ (zi-do´vu-dēn) a synthetic nucleoside (thymidine) analogue that inhibits replication of some retroviruses, including the human immunodeficiency virus; used in the treatment of HIV infection and AIDS.

zidovudine

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

zidovudine (ZDV)

[zīdov′ədēn]
a pyrimidine nucleoside analog active against human immunodeficiency virus. Formerly called azidothymidine.
indications Its function is to inhibit the reverse transcriptase enzyme of the human immunodeficiency virus (HIV). It is used in combination with other antiretroviral medications in the management of patients with HIV infection who have some evidence of impaired immunity. It also may be used for prophylaxis after exposure to HIV.
contraindications It must be used cautiously in patients with impaired renal or hepatic function. It must also be used cautiously in patients with preexisting bone marrow suppression.
adverse effects Headache, GI disturbances, insomnia, flulike symptoms, rash, fatigue, myalgia, and central nervous system symptoms may occur during the first weeks of therapy. The drug may cause granulocytopenia and macrocytic anemia, particularly in patients with advanced HIV disease.

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.

zidovudine (zī·dōˑ ·vyōō·dēnˈ),

n an antiviral drug used to treat HIV-infected patients.

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 (zidō´voodēn´),

n brand names: AZT, Retrovir;
drug class: antiviral thymidine analog;
action: inhibits replication of viral DNA;
uses: symptomatic HIV infections (AIDS, ARC), confirmed
P. jiroveci pneumonia, or absolute CD4 lymphocytes of less than 200 ml; prevention of HIV transmission from an infected mother to her baby.

zidovudine