Zidovudine

Registered South African indications:

• HIV infection

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients 
• Abnormally low neutrophil counts (less than 0.75 x 10⁹/litre)  
• Abnormally low haemoglobin levels (< 7.5g/decilitre)
• Newborn infants with hyperbilirubinaemia requiring treatment other than phototherapy
• Newborn infants with increased transaminase levels of over five times the upper limit of normal

Cautions

• Severe renal impairment
• Hepatic impairment
• Elderly
• Anaemia
• Poor bone marrow reserve prior to treatment
• Advanced symptomatic HIV disease
• Obese females
• Hepatomegaly
• Hepatitis
• Risk factors for liver disease or hepatic steatosis
• Co-infection with hepatitis C and treated with alpha interferon and ribavirin
• Alcoholism
• Symptomatic hyperlactataemia
• Metabolic/lactic acidosis
• Pre-existing liver dysfunction
• Pre-existing neurological disorders
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: cap, tab, sol, syr, inj

HIV infection

• Oral (tab, cap, syr, sol): 300mg, 12hrly

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Can be reduced to 200mg, 12hrly if needed for haematological toxicity

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• IV: 1-2mg/kg, over 1hr, 4hrly

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Dilute in 5% glucose to give zidovudine concentration of 2-4mg/ml

Given as slow IV infusion

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Prevention of mother to child transmission of HIV

From 14 weeks pregnancy

• Oral (cap, tab, syr, sol): 300mg, 12hrly

From onset of labour to delivery

• Oral (cap, tab, syr, sol): 300mg, 3hrly

HIV post exposure prophylaxis

• Oral (cap, tab, syr, sol): 300mg, 12hrly; Treatment duration: 4 weeks

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In combination with tenofavir, lamivudine and atazanir/ritonavir or lopinavir/ritonavir

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Do not use as monotherapy

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Do not give IM

Paed. forms avail. in SA and covered in this monograph: tab, cap, syr, sol, inj

HIV infection

1 month - 12 years

• Oral (syr,sol, cap,tab): 180-240mg/m², 12hrly; Max: 600mg/24hrs

Neonates for prevention of mother to child transmission of HIV

Premature infants

• Oral (syr,sol): 1.5mg/kg, 12hrly; Treatment duration: 14 days then as for term neonates

Neonates

• Oral (syr, sol, cap, tab): 2mg/kg, 6hrly OR 4mg/kg, 12hrly
• IV: 1.5mg/kg, 8hrly infused over 30min

Weight	Dose	Syrup (10mg/ml)	Age
2-2.5kg	10mg	1ml	birth - 6 weeks
>2.5kg	15mg	1.5ml	>6 weeks

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Initiate within 12hrs of birth, continue for first 6 weeks of life

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HIV post exposure prophylaxis

• Oral (syr, sol): 180-240mg/m²; Max: 300mg/dose 

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In combination with lamivudine and lopinavir/ritonavir

Consult HIV/infectious disease specialists prior to any decisions related to ARV regimen termination/switch

Pregnancy

• Safe  
• As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, the animal data, as well as the clinical experience in pregnant women, should be taken into account. In the present case, the use in pregnant women of zidovudine, with subsequent treatment of the newborn infants, has been shown to reduce the rate of maternal-foetal transmission of HIV. A large amount of data on pregnant women (more than 3000 outcomes from first trimester and more than 3000 outcomes from second and third trimester exposure) indicate no malformative toxicity. Zidovudine can be used during pregnancy if clinically needed. The malformative risk is unlikely in humans based on the mentioned large amount of data
• Zidovudine has been associated with reproductive toxicity findings in animal studies. The active ingredients of zidovudine may inhibit cellular DNA replication and zidovudine has been shown to be a transplacental carcinogen in one animal study. The clinical relevance of these findings is unknown. Placental transfer of zidovudine has been shown to occur in humans
• Mitochondrial dysfunction: nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable degree of mitochondrial damage. There have been reports of mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally to nucleoside analogues

Breastfeeding

• Compatible
• After administration of a single dose of 200 mg zidovudine to HIV-infected women, the mean concentration of zidovudine was similar in human milk and serum. Breastfeeding mothers may breastfeed their infants
• South African HIV guidelines recommend exclusive breastfeeding for the first 6 months, after which the nutritional needs of the child will require the introduction of complementary foods, while breastfeeding continues. Mothers failing second or third line regimens should not breastfeed, provided the mother fulfils the AFASS (affordable, feasible, acceptable, sustainable and safe) criteria

Fertility

• Zidovudine did not impair male or female fertility in rats given oral doses of up to 450mg/kg/day. There is no data on the effect of zidovudine on human female fertility
• In men, zidovudine has not been shown to affect sperm count, morphology or motility

Renal Impairment

• CrCl 10-50ml/min: No dose adjustment recommended
• CrCl <10 ml/min: Caution; dose adjustment recommended

CrCl	Dose
10-50	No dose adjustment necessary
<10	300mg daily
Hemodialysis	300mg daily; After dialysis

Hepatic Impairment

• Caution; dose adjustment may be recommended
  Reduce dose by 50% or double dose interval in significant hepatic impairment

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Anxiety
• Depression
• Headache
• Dizziness
• Convulsions
• Loss of mental acuity
• Insomnia
• Paraesthesia
• Somnolence
• Malaise
• Asthenia

Cardiovascular Disorders

•  Cardiomyopathy

Respiratory Disorders

• Dyspnoea
• Cough

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Abdominal pain
• Flatulence
• Oral mucosa pigmentation
• Dyspepsia
• Pancreatitis

Hepatobiliary Disorders

• Raised blood levels of liver enzymes
• Raised blood levels bilirubin
• Severe hepatomegaly with steatosis
• Autoimmune hepatitis

Genitourinary Disorders

• Urinary frequency
• Gynaecomastia

Endocrine and Metabolic Disorders

• Lactic acidosis in the absence of hypoxaemia
• Anorexia
• Increased weight
• Increased blood lipids
• Increased glucose

Musculoskeletal Disorders

• Myalgia
• Myopathy
• Osteonecrosis

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritis
• Urticaria
• Nail pigmentation
• Skin pigmentation
• Sweating
• Lipoatrophy

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Neutropenia
• Leucopenia
• Pancytopenia with bone marrow hypoplasia
• Thrombocytopenia
• Pure red cell aplasia
• Aplastic anaemia

Sensory Disorders

• Taste disturbance

Others

• Fever
• Generalised pain
• Chest pain and influenza-like syndrome
• Chills
• Grave's disease

• Rifampicin 
• Stavudine 
• Probenecid 
• Phenytoin
• Valproic acid
• Fluconazole  
• Methadone
• Ribavirin
• Nephrotoxic agents
• Myelosuppressive agents
• Systemic pentamidine
• Dapsone
• Pyrimethamine
• Co-trimoxazole
• Amphotericin
• Flucytosine
• Ganciclovir
• Interferon
• Vincristine
• Vinblastine
• Doxorubicin
• Clarithromycin
• Atovaquone

• Full blood count
• Hepatic function
• Blood creatinine
• HIV viral load
• CD4 count

Specific cases may require

• Blood lipids
• Blood glucose

Zidovudine is an antiviral agent, which is highly active in vitro against retroviruses including the Human Immunodeficiency Virus (HIV). Zidovudine is phosphorylated in both infected and uninfected cells to the monophosphate (MP) derivative by cellular thymidine kinase. Subsequent phosphorylation of zidovudine-MP to the diphosphate (DP), and then the triphosphate (TP) derivative is catalysed by cellular thymidylate kinase and non-specific kinases respectively. Zidovudine-TP acts as an inhibitor of and substrate for the viral reverse transcriptase. The formation of further proviral DNA is blocked by incorporation of zidovudine-MP into the chain and subsequent chain termination. Competition by zidovudine-TP for HIV reverse transcriptase is approximately 100-fold greater than for cellular DNA polymerase alpha.

Capsule 100mg

• Aspen Zidovudine (Pharmacare)
• Cipla-Zidovudine (Cipla Medpro)
• Dizovin (Macleods)
• Dozra (Novagen)
• Retrovir (GSK) originator

Capsule 250mg

• Aspen Zidovudine (Pharmacare)
• Retrovir (GSK) originator

Tablet 100mg

• Zidomat (Mylan)

Tablet 300mg

• Adco-Zidovudine (Adcock)
• Aspen Zidovudine (Pharmacare)
• Cipla Duovir (Cipla Medpro)
• Cipla Zidovudine (Cipla Medpro)
• Colamziv (LeBassi)
• Dizovin (Macleods)
• Dozra (Novagen)
• Retrovir (GSK) originator
• Sonke Zidovudine (Ranbaxy)
• Vari-Zidovudine (LeBassi)
• Zidomat (Mylan)

Solution (per 5ml) 50mg

• Cipla Zidovudine (Cipla Medpro)
• Dozra (Novagen)

Syrup (per 5ml) 50mg

• Adco-Zidovudine (Adcock)
• Adco-Zidovudine Syrup Alcohol and Sugar Free  (Adcock)
• Aspen Zidovudine (Pharmacare)
• Pharma-Q Zidovudine (Pharma Q)
• Retrovir (GSK) originator

Injection (per 20ml) 200mg

• Retrovir (GSK) originator

COMBINATION PREPARATIONS

Lamivudine/ Zidovudine

150mg/ 300mg

• Cipla Duovir (Cipla Medpro)

Abacavir/ Lamivudine/ Zidovudine

Tablet 300mg/150mg/300mg

• Sonke Abaclamizid (Ranbaxy)
• Trizivar (GSK) originator

Zidovudine/ Lamivudine/ Nevirapine

Tablet 300mg/200mg/150mg

• Mivirido (Mylan)
• Triplavar (Cipla Medpro)