Lamivudine/ Zidovudine/ Nevirapine

Registered South African indications: 

• HIV-1  infection

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

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

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

Nevirapine
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Severe hepatic impairment  
• Readministration to patients who have had prior severe rash, rash accompanied by constitutional symptoms, hypersensitivity reactions, or clinical hepatitis due to nevirapine
• AST or ALT >5 times ULN (pretreatment or during prior nevirapine therapy)
• Coadministration with St. John's wort

Cautions

• Breastfeeding
• Renal impairment
• Moderate hepatic impairment
• Elderly
• Should not be used as monotherapy
• Dose must be strictly adhered to, especially the 14-days lead-in period
• Chronic hepatitis B or C 
• Post exposure prophylaxis 

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

HIV infection

Lamivudine/ Zidovudine/ Nevirapine
150/300/200 (mg)

• Oral (tab): 1 tab, 12hrly

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 C (Zidovudine, Lamivudine) 

Breastfeeding

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

Renal Impairment

• Caution; dose adjustment recommended (Nevirapine) 

Hepatic Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Contraindicated (Nevirapine)

Elderly

• Caution; no information available (Zidovudine, Nevirapine)

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

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

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

Nevirapine
Central Nervous System Disorders

• Headache
• Fatigue

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain
• Diarrhoea

Hepatobiliary Disorders

• Hepatitis 
• Life-threatening hepatotoxicity
• Jaundice
• Hepatitis fulminant (which may be fatal)

Musculoskeletal Disorders

• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Rash 
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis 
• Angioedema
• Urticaria

Immune, Blood and Lymphatic System Disorders

• Granulocytopenia
• Anaemia
• Hypersensitivity 
• Anaphylactic reaction
• Drug reaction with eosinophilia and systemic symptoms

Others

• Pyrexia

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

Lamivudine

• Trimethoprim/sulfamethoxazole
• Cladribine
• Cytidine analogues
• Zalcitabine

Zidovudine

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

Nevirapine

• P450 substrates
• Zidovudine
• Non-nucleoside reverse transcriptase inhibitors
• Indinavir
• Atazanavir/ritonavir
• Fosamprenavir
• Lopinavir/ritonavir
• Elvitegravir/ cobicistat
• Clarithromycin
• Rifabutin
• Rifampicin
• Fluconazole
• Itraconazole
• Ketoconazole
• Boceprevir
• Telaprevir
• Warfarin
• Oral hormonal contraceptives
• Methadone
• St. John's Wort

• Full blood count
• Hepatic function

Specific cases may require

• Lipid profile
• Blood glucose

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.

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. 

Nevirapine
Nevirapine is a non-competitive, non-nucleoside reverse transcriptase inhibitor of HIV-1. It binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities.

COMBINATION PREPARATIONS

Lamivudine/ Zidovudine/ Nevirapine

Tablet 150mg/300mg/200mg

• Mivirdo (Mylan)
• Triplavar (Cipla)