Abacavir

Registered South African indications:

• HIV-1 infection

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Severe hepatic impairment
• Presence of the HLA-B*5701 allele

Cautions

• Breastfeeding
• Renal impairment
• Mild to moderate hepatic impairment
• High viral load (>100 000 copies/ml)
• Long term exposure to combination antiretroviral therapy
• Myocardial infarction
• Opportunistic infections
• Co-infection with chronic hepatitis B or C virus
• Fructose intolerance (sol)

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

First line treatment of HIV infection with contraindication to tenofovir 

• Oral (tab): 300-600mg, 12-24hrly, plus lamivudine and efavirenz or nevirapine
• Oral (sol): 15-30ml, 12-24hrly, plus lamivudine and efavirenz or nevirapine

Second line treatment with anaemia and renal failure

• Oral (tab): 300-600mg, 12-24hrly, plus lamivudine and lopinavir/ritonavir
• Oral (sol): 15-30ml, 12-24hrly, plus lamivudine and lopinavir/ritonavir

Do not use as monotherapy

Has the potential to cause a life-threatening hypersensitivity reaction

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

HIV infection

Younger than 3 months

• Not established for use 

Between 3 months - 12 years

• Oral (sol): 8mg/kg, 12hrly OR 16mg/kg, dly; Max: 600mg/24hrs

Older than 12 years

• See adult dosage

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 HIV infection in pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, both animal data, as well as clinical experience in pregnant women, should be taken into account
• Animal studies have shown toxicity to the developing embryo and foetus in rats, but not in rabbits. Abacavir has been shown to be carcinogenic in animal models. Clinical relevance in human of these data is unknown. Placental transfer of abacavir and/or its related metabolites have been shown to occur in humans  
• In pregnant women, more than 800 outcomes after first-trimester exposure and more than 1000 outcomes after second and third-trimester exposure indicate no malformative and foetal/neonatal effect of abacavir. The malformative risk is unlikely in humans based on those data
• 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

• Caution
• Abacavir and its metabolites are excreted into the milk of lactating rats. Abacavir is also excreted into human milk
• 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 2nd or 3rd line regimens should not breastfeed, provided the mother fulfils the AFASS (affordable, feasible, acceptable, sustainable and safe) criteria

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended
  Reduce dose to 200mg, 12hrly
• Severe: Contraindicated 

Elderly

• No dose adjustment recommended 

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Lethargy 
• Fatigue

Gastrointestinal Disorders

• Nausea and vomiting 
• Diarrhoea
• Pancreatitis

Endocrine and Metabolic Disorders

• Anorexia 
• Lactic acidosis
• Weight changes
• Changes in blood lipid levels
• Changes in blood glucose levels

Skin and Subcutaneous Tissue Disorders

• Rash  
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis

Immune, Blood and Lymphatic System Disorders

• Abacavir hypersensitivity reactions

Other

• Fever

• Alcohol
• Rifampicin
• Phenobarbital
• Phenytoin
• Methadone

• HLA-B*5701 genotype status prior to initiation of therapy and prior to reinitiation of therapy in patients of unknown HLA-B*5701 status
• Full blood count
• Hepatic function  
• Blood glucose
• Lipid profile

Abacavir is a nucleotide reverse transcriptase inhibitor (NRTI). It is a potent selective inhibitor of HIV-1 and HIV-2. It is metabolised intracellularly to the active moiety, carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.

Tablet 60mg

• Kavimun Paed (Mylan) originator

Tablet 300mg

• Adco Abacavir (Adcock)
• Aspen Abacavir (Pharmacare)
• Bavir (Aurobindo)
• Cipla Abacavir (Cipla Medpro)
• Hetacav 300 (Hetero Drugs)
• Invertron (Novagen)
• Kavimun (Mylan)
• Sonke Abacavir (Ranbaxy)
• Ziagen (GSK) originator

Oral solution (per ml) 20mg

• Adco Abacavir (Adcock)
• Aspen Abacavir (Pharmacare)
• Bavir oral solution (Aurobindo)
• Cipla Abacavir (Cipla Medpro)
• Hetacav Oral Solution Hetero (Hetero Drugs)
• Invertron Oral solution ( Novagen)
• Ziagen (GSK) originator

COMBINATION PREPARATIONS

Abacavir/ Lamivudine

Tablet 600mg/300mg

• Abacavir & Lamivudine Cipla (Cipla Medpro)
• Auro Abacavir Lamivudine (Aurobindo Pharma)
• Dumiva (Mylan)
• Heteruam 600/300mg (Hetero)
• Kivexa (GSK)

Abacavir/ Lamivudine/ Zidovudine

Tablet 300mg/150mg/300mg

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

Dolutegravir/ Abacavir/ Lamivudine

Tablet 50mg/600mg/300mg

• Trelavue (GSK) originator