Zidovudine/ Lamivudine/ Abacavir

Registered South African indications:

• HIV infection

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Zidovudine
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Abnormally low neutrophil counts (less than 0.75 x 10⁹/litre)  
• Abnormally low haemoglobin levels (< 8 g/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

• Pregnancy
• Breastfeeding
• Severe renal impairment
• Hepatic impairment 
• Elderly

Abacavir
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Moderate to severe hepatic impairment
• Presence of the HLA-B*5701 allele

Cautions

• Breastfeeding
• Severe renal impairment
• Mild hepatic impairment
• Elderly
• 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

Lamivudine
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product

Cautions

• Pregnancy
• Breastfeeding
• Moderate to severe renal impairment
• Hepatic impairment
• Not recommended for use as monotherapy
• Pancreatitis
• Diabetes mellitus
• HIV-1 resistance may emerge in chronic hepatitis B-infection patients with unrecognized or untreated HIV-1 infection

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

HIV infection

Zidovudine/ Abacavir/ Lamivudine
300/300/150 (mg)

• Oral (tab): 1 tab, 12hrly

---

Not suitable for patients <40kg

Not established for use in children below 12 years

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

Recommendations for this combination product as per highest risk category when comparing individual active ingredients

Pregnancy

• FDA Pregnancy Category Not Rated (NR) (Abacavir) 

Breastfeeding

• Caution; not recommended (Zidovudine, Abacavir, Lamivudine)

Renal Impairment

• Severe: Caution; dose adjustment recommended (Zidovudine) 

Hepatic Impairment

• Mild: Caution; dosage adjustment recommended (Zidovudine)
• Moderate to severe: Contraindicated (Abacavir)

Elderly

• Caution; no information available (Zidovudine, Abacavir)

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Zidovudine
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
• Taste disturbance
• Dyspepsia
• Pancreatitis

Hepatobiliary Disorders

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

Genitourinary Disorders

• Urinary frequency
• Gynaecomastia

Endocrine and Metabolic Disorders

• Lactic acidosis in the absence of hypoxaemia
• Anorexia

Musculoskeletal Disorders

• Myalgia
• Myopathy

Skin and Subcutaneous Tissue Disorders

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

Immune, Blood and Lymphatic System Disorders

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

Others

• Fever
• Generalised pain
• Chest pain and influenza-like syndrome
• Chills

Abacavir
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

Lamivudine
Central Nervous System Disorders

• Headache
• Insomnia
• Peripheral neuropathy

Respiratory Disorders

• Cough
• Nasal symptoms

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain 
• Diarrhoea
• Pancreatitis
• Elevations in serum amylase

Hepatobiliary Disorders

• Transient elevations in liver enzymes
• Hepatitis

Endocrine and Metabolic Disorders

• Lactic acidosis

Musculoskeletal Disorders

• Arthralgia
• Muscle disorders
• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Rash
• Alopecia
• Angioedema

Immune, Blood and Lymphatic System Disorders

• Neutropenia
• Anaemia 
• Thrombocytopenia
• Pure red cell aplasia

Others

• Fatigue
• Malaise
• Fever

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Zidovudine

• Rifampicin
• Stavudine
• Probenecid  
• Phenytoin 
• Valproic acid 
• Fluconazole  
• Methadone 
• Ribavirin 
• Nephrotoxic agents 
• Myelosuppressive agents 
• Clarithromycin

Abacavir

• Alcohol
• Rifampicin
• Phenobarbital
• Phenytoin
• Methadone

Lamivudine

• Trimethoprim/sulfamethoxazole
• Cladribine
• Cytidine analogues
• Zalcitabine

• 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

Zidovudine
Zidovudine, a structural analog of thymidine, is a prodrug which is phosphorylated to its active 5′-triphosphate metabolite, zidovudine triphosphate. Zidovudine-TP inhibits HIV-1 reverse transcriptase via DNA chain termination, after incorporation of the nucleotide analogue. 

Abacavir
Abacavir is a nucleotide reverse transcriptase inhibitor. 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.

Lamivudine
Lamivudine is a nucleoside analogue which has activity against human immunodeficiency virus (HIV) and hepatitis B virus (HBV). It is metabolised intracellularly to the active moiety, lamivudine 5'-triphosphate. Its main mode of action is as a chain terminator of viral reverse transcription. The triphosphate has selective inhibitory activity against HIV-1 and HIV-2 replication and is also active against zidovudine-resistant clinical isolates of HIV.

COMBINATION PREPARATIONS

Zidovudine/Abacavir/Lamivudine

Tablet 300mg/300mg/150mg

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