Intravenous Prophylaxis of maternal-fetal HIV transmission during labour and delivery
Adult: In HIV-positive pregnant women: 2 mg/kg (diluted up to a Max concentration of 4 mg/mL) via infusion over 1 hour, followed by 1 mg/kg/hour via continuous infusion until the umbilical cord is clamped. For planned caesarean section, start the infusion 3 or 4 hours before the operation.
Intravenous HIV infection
Adult: For short-term management of patients who are unable to take oral therapy: 1 mg/kg or 2 mg/kg 4 hourly (diluted to a concentration of up to 4 mg/mL) via slow infusion over 1 hour. Continue treatment until oral therapy can be substituted. Dose reduction, dosing interruption, or discontinuation may be required according to the severity of the patient's laboratory parameters (refer to specific product guidelines). Child: In patients who are unable to take oral therapy: 80-160 mg/m2 6 hourly (diluted to a concentration of up to 4 mg/mL) via slow infusion over 1 hour. Continue treatment until oral therapy can be substituted. Dose reduction, dosing interruption, or discontinuation may be required according to the severity of the patient's laboratory parameters (refer to specific product guidelines).
Oral HIV infection
Adult: In combination with other antiretroviral agents: 250 mg or 300 mg bid. Dose reduction, dosing interruption, or discontinuation may be required according to the severity of the patient's laboratory parameters (refer to specific product guidelines). Child: As cap: Patients weighing 8-13 kg: 100 mg bid; 14-21 kg: 100 mg in the morning, then 200 mg in the evening; 22-30 kg: 200 mg bid; ≥30 kg: Same as adult dose. As tab or oral solution/syrup: Infants ≥4 weeks Patients weighing 4-<9 kg: 12 mg/kg bid or 8 mg/kg tid; 9-<30 kg: 9 mg/kg bid or 6 mg/kg tid; ≥30 kg: Same as adult dose. Alternatively, 240 mg/m2 bid or 160 mg/m2 tid. Doses are given with other antiretroviral agents and must not exceed the recommended adult dose. Dose reduction, dosing interruption, or discontinuation may be required according to the patient's haematological parameters (refer to specific product guidelines).
Oral Prophylaxis of maternal-fetal HIV transmission
Adult: In HIV-positive pregnant women (over 14 weeks of gestation): 100 mg 5 times daily until the beginning of labour. Dose reduction, dosing interruption, or discontinuation may be required according to the severity of the patient's laboratory parameters (refer to specific product guidelines).
Renal Impairment
Oral: Patients with ESRD maintained on haemodialysis or peritoneal dialysis: 100 mg 6-8 hrly.
CrCl (mL/min)
Dosage
<15
100 mg 6-8 hrly.
Dosage adjustment may be required according to the patient's haematological parameters and clinical response (refer to specific product guidelines).
Intravenous:
Patients with ESRD maintained on haemodialysis or peritoneal dialysis: 1 mg/kg 6-8 hrly.
CrCl (mL/min)
Dosage
<15
1 mg/kg 6-8 hrly.
Dosage adjustment may be required according to the patient's haematological parameters and clinical response (refer to specific product guidelines).
Administration
May be taken with or without food.
Reconstitution
IV infusion: Solution must be diluted before administration. Dilute the required dose with dextrose 5% in water up to a concentration of 4 mg/mL.
Contraindications
Hypersensitivity. Abnormally low neutrophil counts (<750 cells/mm3) or Hb levels (<7.5 g/dL or <4.65 mmol/L). Newborn infants with hyperbilirubinaemia requiring treatment other than phototherapy or with markedly increased transaminase levels (>5 times the ULN). Lactation.
Special Precautions
Patient with risk factors for liver disease and hepatic steatosis (e.g. obesity, alcohol abuse); bone marrow compromise (granulocytes <1,000 cells/mm3 or Hb <9.5 g/dL). Concomitant use with ribavirin is not recommended. Severe renal and moderate to severe hepatic impairment. Neonates, children, and elderly. Pregnancy.
Adverse Reactions
Significant: Haematological toxicities (e.g. anaemia, neutropenia, leucopenia), lipoatrophy, increased weight, blood lipids, and glucose levels; myopathy and myositis (prolonged use), immune reconstitution syndrome (activation of cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, Pneumocystis jirovecii pneumonia, Graves' disease, autoimmune hepatitis, Guillain-Barre syndrome); osteonecrosis (particularly in advanced HIV disease or chronic exposure to combination antiretroviral therapy); mitochondrial dysfunction (following exposure of infants in utero). Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, constipation. General disorders and administration site conditions: Malaise. Investigations: Increased liver enzymes and bilirubin. Metabolism and nutrition disorders: Anorexia, hyperlactataemia. Musculoskeletal and connective tissue disorders: Myalgia. Nervous system disorders: Headache, dizziness. Potentially Fatal: Lactic acidosis associated with hepatomegaly and hepatic steatosis.
Monitoring Parameters
Monitor haematological parameters (more frequently in patients with poor bone marrow reserve), LFTs, serum creatinine, HIV viral load and CD4 count, lipids, and glucose. Assess for signs of lipoatrophy, haematologic toxicities, opportunistic infections, lactic acids, and hepatomegaly.
Overdosage
Symptoms: Headache, fatigue, vomiting, dizziness, drowsiness, confusion, lethargy, and haematological disturbances. Management: Supportive and symptomatic treatment. Monitor for evidence of toxicity. May consider inducing emesis and administering activated charcoal to prevent further absorption of unrecovered drug.
Drug Interactions
Increased risk of anaemia with ribavirin (particularly in patients co-infected with HCV). Antagonistic effects with stavudine or doxorubicin. Increased plasma level with probenecid, lamivudine, atovaquone, valproic acid, fluconazole, or methadone. May alter plasma phenytoin concentrations. May increase the risk of haematologic toxicity with myelosuppressive agents (e.g. systemic pentamidine, dapsone, pyrimethamine, sulfamethoxazole + trimethoprim, amphotericin B, flucytosine, ganciclovir, interferon alfa, vinca alkaloids, doxorubicin). Reduced absorption with clarithromycin. Decreased plasma concentration with rifampicin, which may result in partial or total loss of efficacy.
Action
Description: Mechanism of Action: Zidovudine, a synthetic nucleoside analogue, is converted intracellularly to its active metabolite, zidovudine triphosphate. It inhibits viral replication by interfering with the viral RNA-dependent DNA polymerase. Pharmacokinetics: Absorption: Well absorbed from the gastrointestinal tract. Bioavailability: Approx 60-70%. Time to peak plasma concentration: 0.5-1.5 hours. Distribution: Crosses the placenta and blood-brain barrier; enters breast milk. Volume of distribution: 1-2.2 L/kg. Plasma protein binding: 34-38%. Metabolism: Metabolised in the liver mainly to inactive glucuronide; undergoes extensive first-pass effect. Excretion: Via urine (oral: 72-74% as metabolites, 14-18% as unchanged drug; IV: 45-60% as metabolites, 18-29% as unchanged drug). Elimination half-life: 1.1 hours (range: 0.5-3 hours).
Chemical Structure
Zidovudine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 35370, Zidovudine. https://pubchem.ncbi.nlm.nih.gov/compound/Zidovudine. Accessed Aug. 18, 2023.
Storage
Store between 15-25°C. Protect from light (intact vials). Protect from moisture (cap). Diluted IV solutions: Stable at room temperature for 24 hours or between 2-8°C for 48 hours.
J05AF01 - zidovudine ; Belongs to the class of nucleoside and nucleotide reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.
References
Anon. Zidovudine (Pediatric and Neonatal Lexi-Drugs). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/05/2023.Anon. Zidovudine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 09/05/2023.Anon. Zidovudine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/05/2023.Buckingham R (ed). Zidovudine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/05/2023.Joint Formulary Committee. Zidovudine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/05/2023.Retrovir 10 mg/mL IV Concentrate for Solution for Infusion (ViiV Healthcare UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 09/05/2023.Retrovir 100 mg/10 mL Oral Solution (ViiV Healthcare UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 09/05/2023.Retrovir 250 mg Capsules, Hard (ViiV Healthcare UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 09/05/2023.Retrovir Capsule; Solution; Injection, Solution (ViiV Healthcare Company). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 09/05/2023.Retrovir Oral Solution (GlaxoSmithKline Pharmaceuticals Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 09/05/2023.Retrovir Vials (GlaxoSmithKline Pharmaceuticals Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 09/05/2023.Zidohope 300 mg Tablets (Paxten Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 09/05/2023.Zidovudine Syrup (Aurobindo Pharma Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 09/05/2023.Zidovudine Tablet, Film Coated (Aurobindo Pharma Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 09/05/2023.Zidovudine, ZDV. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 09/05/2023.
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