Zidovudine

(BAN, USAN, rINN)
Zidovudine Chemical formula
Synonyms: Azidodeoxythymidine; Azidothymidine; AZT; BW-A509U; BW509U; Compound-S; Tsidovudiini; Zidovudin; Zidovudina; Zidovudinas; Zidovudinum; Zydowudyna. 3′-Azido-3′-deoxythymidine.
Cyrillic synonym: Зидовудин.

💊 Chemical information

Chemical formula: C10H13N5O4 = 267.2.
CAS — 30516-87-1.
ATC — J05AF01.
ATC Vet — QJ05AF01.

Pharmacopoeias.

In Eur. and US.

Ph. Eur. 6.2

(Zidovudine). A white or brownish powder. It shows polymorphism. Sparingly soluble in water; soluble in dehydrated alcohol. Protect from light.

USP 31

(Zidovudine). A white to yellowish powder. Exhibits polymorphism. Sparingly soluble in water; soluble in alcohol. Store in airtight containers at a temperature of 25°, excursions permitted between 15° and 30°. Protect from light.

💊 Adverse Effects

The commonest serious adverse effects reported with zidovudine are haematological toxicities such as anaemia, leucopenia, and neutropenia. They occur most commonly when higher doses are used (1.2 to 1.5 g daily) and in patients with advanced HIV disease and a low CD4+ cell count (less than 100 cells/mm 3 ). These haematological toxicities are usually reversed by interrupting treatment or reducing dosage but the anaemia may be severe enough to require blood transfusion. Aplastic anaemia, pure red cell aplasia, pancytopenia, and thrombocytopenia have been rarely reported. Other commonly reported adverse effects include dizziness, headache, malaise, myalgia, and gastrointestinal symptoms such as abdominal pain, diarrhoea, nausea, and vomiting. Long-term use of zidovudine has been associated with myopathy. Raised liver enzymes, hyperbilirubinaemia, lactic acidosis, and severe hepatomegaly with steatosis have been reported as rare, but potentially fatal, occurrences in patients taking zidovudine alone or with other antiretrovirals. Other rare but potentially serious adverse effects include cardiomyopathy, convulsions, and pancreatitis. Immune reconstitution syndrome (an inflammatory immune response resulting in clinical deterioration) has been reported during the initial phase of treatment with combination antiretroviral therapy, including zidovudine, in HIV-infected patients with severe immune deficiency. Accumulation or redistribution of body fat (lipodystrophy) including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance have been seen in patients receiving antiretroviral therapy, including zidovudine. Metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia, and hyperlactataemia have also been reported. NRTIs have also been associated with mitochondrial dysfunction manifesting as abnormal behaviour, anaemia, convulsions, hyperlipasaemia, hypertonia, and neutropenia. Elevated creatine phosphokinase, myalgia, myositis, and rarely rhabdomyolysis have been reported, particularly when nucleoside analogues have been given with HIV-protease inhibitors. Osteonecrosis has been reported, particularly in patients with advanced HIV disease or long-term exposure to combination antiretroviral therapy.

Effects on the blood.

Adverse haematological effects reported with zidovudine may be severe and include anaemia with erythroid aplasia or hypoplasia, and neutropenia.1-5 Although these effects may be reversed by withdrawal,5 they may persist for weeks afterwards2,3 and blood transfusions may be required in some patients.1-4 A study indicated that zidovudine-induced neutropenia only significantly increased the risk of bacterial infection in patients whose polymorphonuclear cell count fell below 500/microlitre.6 The effects of zidovudine on the platelet count are considered to be complex, but patients with thrombocytopenia appeared not to be at risk during treatment.7 Recombinant erythropoietin has been used in an attempt to reduce blood-transfusion requirements in zidovudine-induced anaemia,8,9 although the proportion of patients who derive benefit may be limited and some have reported it to have no effect.10Similarly granulocyte-macrophage colony-stimulating factor has been reported to improve the neutrophil count in some but not all patients.11
1. Forester G. Profound cytopenia secondary to azidothymidine. N Engl J Med 1987; 317: 772
2. Gill PS, et al. Azidothymidine associated with bone marrow failure in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1987; 107: 502–5
3. Mir N, Costello C. Zidovudine and bone marrow. Lancet 1988; ii: 1195–6
4. Walker RE, et al. Anemia and erythropoiesis in patients with the acquired immunodeficiency syndrome (AIDS) and Kaposi sarcoma treated with zidovudine. Ann Intern Med 1988; 108: 372–6
5. Cohen H, et al. Reversible zidovudine-induced pure red-cell aplasia. AIDS 1989; 3: 177–8
6. Shaunak S, Bartlett JA. Zidovudine-induced neutropenia: are we too cautious? Lancet 1989; ii: 91–2
7. Flegg PJ, et al. Effect of zidovudine on platelet count. BMJ 1989; 298: 1074–5
8. Fischl M, et al. Recombinant human erythropoietin for patients with AIDS treated with zidovudine. N Engl J Med 1990; 322: 1488–93
9. Henry DH, et al. Recombinant human erythropoietin in the treatment of anemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy: overview of four clinical trials. Ann Intern Med 1992; 117: 739–48
10. Shepp DH, et al. Erythropoietin for zidovudine-induced anemia. N Engl J Med 1990; 323: 1069–70
11. Hewitt RG, et al. Pharmacokinetics and pharmacodynamics of granulocyte-macrophage colony-stimulating factor and zidovudine in patients with AIDS and severe AIDS-related complex. Antimicrob Agents Chemother 1993; 37: 512–22.

Effects on the CNS.

Reports of adverse effects on the CNS associated with zidovudine include mania,1,2 seizures3,4 (following an overdose in one patient5), psychogenic panic,6 and Wernicke’s encephalopathy,7 mostly involving one or two patients in each case. CNS toxicity, thought to be zidovudine-related, contributed to the death of an AIDS patient.8 For reports of neurological symptoms associated with mitochondrial dysfunction in infants whose mothers received perinatal zidovudine, see Effects on Mitochondria, below.
1. Maxwell S, et al. Manic syndrome associated with zidovudine treatment. JAMA 1988; 259: 3406–7
2. Wright JM, et al. Zidovudine-related mania. Med J Aust 1989; 150: 339–40
3. Harris PJ, Caceres CA. Azidothymidine in the treatment of AIDS. N Engl J Med 1988; 318: 250
4. D’Silva M, et al. Seizure associated with zidovudine. Lancet 1995; 346: 452
5. Routy JP, et al. Seizure after zidovudine overdose. Lancet 1989; i: 384–5
6. Levitt AJ, Lippert GP.
Psychogenic panic after zidovudine therapy—the therapeutic benefit of an N of 1 trial. Can Med A combination of zidovudine and other antiretroviral drugs improves efficacy, minimises toxicity, and delays drug resistance. Results from the Delta study1 and the US AIDS Clinical Trial Group 175 (ACTG 175) study2 showed combination therapy to be more effective than monotherapy in antiretroviral-naive patients and have led to profound changes in clinical practice. Both studies showed substantial reductions in mortality at 30 months in antiretroviral-naive patients treated with zidovudine plus either didanosine or zalcitabine compared with those receiving zidovudine alone. Triple therapy, with zidovudine used with another nucleoside reverse transcriptase inhibitor and either an HIVprotease inhibitor or a non-nucleoside reverse transcriptase inhibitor (HAART regimens), has been found to reduce viral loads more effectively than monotherapy or two-drug combination therapy and such regimens are currently regarded as standard.
1. Delta Coordinating Committee. Delta: a randomised doubleblind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals. Lancet 1996; 348: 283–91
2. Hammer SM, et al. A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter. N Engl J Med 1996; 335: 1081–90.

HIV infection prophylaxis.

Antiretroviral drugs are used for chemoprophylaxis after occupational and non-occupational exposure to HIV infection. Zidovudine is commonly used with other antiretroviral drugs after exposure with a risk of infection. Zidovudine has been shown to be of value in reducing vertical transmission. For further information on the use of zidovudine in preventing HIV transmission from mother to child, see HIV Infection Prophylaxis.

💊 Preparations

USP 31: Zidovudine Capsules; Zidovudine Injection; Zidovudine Oral Solution; Zidovudine Tablets.

Proprietary Preparations

Arg.: Azoazol†; Azotine†; Crisazet; Enper; Exovir†; Iduvo†; Retrovir; Zetrotax; Austral.: Retrovir; Austria: Retrovir; Belg.: Retrovir; Braz.: Produvir; Retrovir; Revirax; Virozid†; Zidovir†; Zidovusan†; Canad.: Novo-AZT†; Retrovir; Chile: Retrovir; Cz.: Retrovir; Denm.: Retrovir; Fin.: Retrovir; Fr.: Retrovir; Ger.: Retrovir; Gr.: Retrovir; Viroclon; Zidrevir; Hong Kong: Retrovir; Hung.: Retrovir; India: Retrovir; Zidorex†; Zidovir; Zilion; Zydowin; Indon.: Retrovir; Irl.: Retrovir; Israel: Retrovir; Ital.: Retrovir; Malaysia: Retrovir; Mex.: Azetavir; Novavir; Pranadox; Retrovir; Timivudin; Zidic-C; Zidovir†; Neth.: Retrovir; Norw.: Retrovir; NZ: Retrovir; Philipp.: Retrovir; Pol.: Azovir; Retrovir; Port.: Ambrodil; Azidina; Hivalase; Retrovir; Virotec; Rus.: Retrovir (Ретровир); S.Afr.: Retrovir; Singapore: Retrovir; Spain: Retrovir; Swed.: Retrovir; Switz.: Retrovir; Thai.: Retrovir; T-ZA; T.O.Vir; Zidis†; Turk.: Retrovir; UK: Retrovir; USA: Retrovir; Venez.: Retrovir; Zidovir. Multi-ingredient: Arg.: 3TC Complex; 3TC/AZT; Ganvirel Duo; Hivirux Complex†; Imunoxa Complex; Kess Complex; Muvidina; Tricivir; Trivudin; Ultraviral Duo; Zetavudin; Austral.: Combivir; Trizivir; Austria: Combivir; Trizivir; Belg.: Combivir; Trizivir; Braz.: Biovir; Duovir†; Vir-Complex†; Zidolam; Canad.: Combivir; Trizivir; Chile: Combivir; Tricivir; Cz.: Combivir; Trizivir; Denm.: Combivir; Trizivir; Fin.: Combivir; Trizivir; Fr.: Combivir; Trizivir; Ger.: Combivir; Trizivir; Gr.: Combivir; Trizivir; Hong Kong: Combivir; Trizivir; Hung.: Combivir; Trizivir; India: Combirex†; Duovir; Duovir N; Lamda-Z; Lamuzid; Irl.: Combivir; Trizivir; Israel: Combivir; Trizivir; Ital.: Combivir; Trizivir; Malaysia: Combivir; Mex.: Combivir; Trizivir; Neth.: Combivir; Trizivir; Norw.: Combivir; Trizivir; NZ: Combivir; Trizivir; Philipp.: Combivir; Pol.: Combivir; Trizivir; Port.: Combivir; Trizivir; Rus.: Combivir (Комбивир); Trizivir (Тризивир); S.Afr.: Combivir; Duovir; Lamzid; Retrovir/3TC Post-HIV Exposure†; Trizivar; Singapore: Combivir; Trizivir†; Spain: Combivir; Trizivir; Swed.: Combivir; Trizivir; Switz.: Combivir; Trizivir; Thai.: Combid; Turk.: Combivir; UK: Combivir; Trizivir; USA: Combivir; Trizivir; Venez.: Combivir; Duovir; Trizivir.
Published October 07, 2018.