Lamivudine/ Stavudine/ 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

Stavudine
Contraindications

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

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• History of severe hyperlactatemia with a nucleotide reverse transcriptase inhibitor
• Co-infection with hepatitis B or C
• History of or risk factors for neuropathy
• History of or risk factors for pancreatitis  
• Long term  exposure to combination antiretroviral therapy

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/ Stavudine/ Nevirapine
150/30/200 (mg)

• Oral (tab): 1 tab, 12hrly

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Not suitable for patients < 30kg or > 60kg

Not established for use in children

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 (Lamivudine, Stavudine) 

Breastfeeding

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

Renal Impairment

• Moderate to severe: Caution; dose adjustment recommended (Lamivudine) 

Hepatic Impairment

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

Elderly

• Caution; no information available (Stavudine, Nevirapine)

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

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
• Fever

Lamivudine
Central Nervous System Disorders

• Headache
• Insomnia
• Peripheral neuropathy
• Malaise

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
• Fever

Stavudine
Central Nervous System Disorders

• Depression
• Anxiety
• Emotional lability 
• Peripheral neuropathy
• Paresthesia
• Peripheral neuritis
• Dizziness
• Abnormal dreams
• Headache
• Insomnia
• Abnormal thinking
• Somnolence
• Motor weakness
• Fatigue

Gastrointestinal Disorders

• Diarrhoea
• Abdominal pain
• Nausea and vomiting
• Dyspepsia
• Pancreatitis

Hepatobiliary Disorders

• Hepatitis
• Jaundice
• Hepatic steatosis
• Hepatic failure

Endocrine and Metabolic Disorders

• Gynaecomastia 
• Lipoatrophy
• Asymptomatic hyperlactatemia
• Lactic acidosis 
• Anorexia
• Hyperglycaemia
• Diabetes mellitus
• Increase in blood lipid levels 
• Increase in blood glucose levels 
• Mitochondrial dysfunction

Musculoskeletal Disorders

• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Rash 
• Prutitis
• Urticaria

Immune, Blood and Lymphatic System Disorders

• Anaemia 
• Neutropenia
• Thrombocytopenia 

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

Lamivudine

• Trimethoprim/sulfamethoxazole
• Cladribine
• Cytidine analogues
• Zalcitabine

Stavudine

• Didanosine
• Medicinal products which are actively secreted by the renal tubules  
• Zidovudine
• Doxorubicin
• Ribavirin
• Drugs known to cause pancreatitis or peripheral neuropathy

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 at 2, 4, 8 weeks; and periodically thereafter

Specific cases may require

• Renal function
• 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.

Stavudine
Stavudine is a synthetic thymidine nucleoside analogue. It enters cells by diffusion and is phosphorylated by cellular kinases to the active metabolite stavudine triphosphate. It inhibits HIV reverse transcriptase by competing with the natural substrate, thymidine triphosphate. It also inhibits viral DNA synthesis by causing DNA chain termination due to a lack of the 3'-hydroxyl group necessary for DNA elongation. It further inhibits cellular DNA polymerase and gamma, and markedly reduces the synthesis of mitochondrial DNA.

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/ Stavudine/ Nevirapine

Tablet 150mg/30mg/200mg

• Nevasta (Emcure)
• Sonke-Laminevstav 30 (Ranbaxy)
• Triomune (Cipla)
• Tri-Nestlam (Adcock Ingram)
• Virtrium 30/150/200 (Pharmacare)