Lamivudine

Registered South African indications:

• HIV infection

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Moderate to severe renal impairment (eGFR ≤50ml/min/1.73m²)
• 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
• Fructose intolerance (syr)
• Glucose-galactose malabsorption (syr)
• Sucrase-isomaltase insufficiency (syr)

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

HIV infection

• Oral (tab, syr, sol): 300mg, dly OR 150mg, 12hrly

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In combination with abacavir, lopinavir/ritonavir or efavirenz

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HIV post exposure prophylaxis

• Oral (tab, syr, sol): 150mg, 12hrly; Treatment duration: 4 weeks

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In combination with tenofovir, atazanavir/ritonavir or lopinavir/ritonavir

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Prevention of mother to child transmission of HIV

• Oral (tab, syr, sol): 300mg, daily

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In combination with tenofovir and efavirenz

Do not use as monotherapy

Tablet formulation for patients who weigh at least 14kg 

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See additional prescribing points for changing dosing regimen

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Chronic Hepatitis B infection without HIV co-infection

• Oral (tab, syr, sol): 100-150mg, daily

Chronic Hepatitis B infection with HIV co-infection

• Oral (tab, syr, sol): 300mg, daily OR 150mg, 12hrly

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

HIV infection

Neonates <30 days

• Oral (tab, syr, sol): 2mg/kg, dly

Between 3 months - 12 years

• Oral (tab, syr, sol): 4mg/kg, 12hrly; Max: 300mg/24hrs

OR

>10kg

• Oral (tab, syr, sol): 8mg/kg, dly

HIV post exposure prophylaxis

• Oral (tab, syr, sol): 4mg/kg, 12hrly OR 8mg/kg, dly; Treatment duration: 28 days; Max dose: 150mg if given 12hrly; 300mg if given daily

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In combination with zidovudine or lopinavir/ritonavir

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See additional prescribing points for changing dosing regimen

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. Animal studies with lamivudine showed an increase in early embryonic deaths in rabbits but not in rats. Placental transfer of lamivudine has been shown to occur in humans
• More than 1000 outcomes from first trimester and more than 1000 outcomes from second and third trimester exposure in pregnant women indicate no malformative and foetal/neonatal effect. Lamivudine can be used during pregnancy if clinically needed. The malformative risk is unlikely in humans based on those data. For patients co-infected with hepatitis who are being treated with lamivudine and subsequently become pregnant, consideration should be given to the possibility of a recurrence of hepatitis on discontinuation of lamivudine
• 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 infants exposed in utero and/or post-natally to nucleoside analogues

Breastfeeding

• Compatible
• Breastfeeding following oral administration lamivudine was excreted in breast milk at similar concentrations to those found in serum. Based on more than 200 mother/child pairs treated for HIV, serum concentrations of lamivudine in breastfed infants of mothers treated for HIV are very low and progressively decrease to undetectable levels when breastfed infants reach 24 weeks of age. 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 2nd or 3rd line regimens should not breastfeed, provided the mother fulfills the AFASS (affordable, feasible, acceptable, sustainable and safe) criteria

Renal impairment

• eGFR>50ml/min/1.73m²: No dose adjustment recommended
• eGFR≤50ml/min/1.73m²: Caution; dose adjustment recommended 

eGFR (ml/min/1.73m2)	Adult and Children ≥ 25kg
>50	No adjustment necessary
≥10-50	150mg, dly
<10	50mg, dly
Haemodialysis/ Peritoneal dialysis (PD)	Loading dose: 50mg; Maintenance: 25mg, dly; Administer dose after dialysis

 

eGFR (ml/min/1.73m2)	Children < 25kg
>50	No adjustment necessary
≥30-50	4mg/kg/dose, dly
10-29	2mg/kg/dose, dly
<10	1mg/kg/dose, dly
Intermittent hemodialysis (IHD)/ Peritoneal dialysis (PD)	1mg/kg/dose, dly
Continuous renal replacement therapy (CRRT)	4mg/kg/dose, dly

Hepatic impairment

• Caution; no dose adjustment recommended

Elderly

• No dose adjustment recommended 

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

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

• Trimethoprim/sulfamethoxazole
• Cladribine
• Cytidine analogues
• Zalcitabine

None routine

Changing dosing regimen

Patients changing from the 12hrly dosing regimen to the daily dosing regimen should take the recommended once daily dose approximately 12 hours after the last 12hrly dose, and then continue to take the recommended once daily dose approximately every 24hrs. When changing back to a 12hrly regimen, patients should take the recommended 12hrly dose approximately 24hrs after the last once daily dose

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.

Syrup (per ml) 10mg

• Aspen Lamivudine (Pharmacare)
• Pharma-Q Lamivudine (Pharma Q)

Solution (per ml) 10mg

• 3TC (GSK) originator
• Adco Lamivudine (Adcock)
• Bindolam (Aurobindo)
• Legram (Novagen)
• Cipla Lamivudine (Cipla Medpro)

Tablet 150mg

• 3TC (GSK) originator
• Adco Lamivudine (Adcock)
• Aspen Lamivudine (Pharmacare)
• Cipla Lamivudine (Cipla Medpro)
• Hetlam (Hetero)
• Lamivudine Winthrop (Zentiva) (Discontinued: 16/07/2018)
• Lazena (Mylan)
• Legram (Novagen)
• Macleods Lamivudine (Macleods)
• Sonke-Lamivudine (Ranbaxy)
• Vari-Lamivudine (LeBasi)

Tablet 300mg

• Adco Lamivudine (Adcock Ingram)
• Cipla Lamivudine (Cipla Medpro)
• Lazena (Mylan)

COMBINATION PREPARATIONS

Lamivudine/ Zidovudine

Tablet 150mg/300mg

• Adco Lamivudine and Zidovudine (Adcock)
• Aspen Lamzid (Pharmacare)
• Cipla Duovir (Cipla Medpro)
• Combivir (GSK) originator
• Combozil 150/300 (Hetero)
• Divuwin (Sanofi)
• Lodiz (Novagen)
• Retrovir/3TC starter pack (GSK) originator
• Sonke Lamivudine+Zidovudine (Ranbaxy) originator
• Zovilam (Mylan)

Lamivudine/ Tenofovir

Tablet 300mg/300mg

• Cipla Lamivudine & Tenofovir (Cipla Medpro)

Abacavir/ Lamivudine

Tablet 600mg/300mg

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

Abacavir/ Lamivudine/ Zidovudine

Tablet 300mg/150mg/300mg

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

Stavudine/ Lamivudine/ Nevirapine

Tablet 30mg/150mg/200mg

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

Efavirenz/ Lamivudine/ Tenofovir

Tablet 600mg/300mg/300mg

• Arion (Novagen)
• Eflaten (Mylan)
• Tenarenz (Pharmacare)
• Virlaten (Sandoz)

Efavirenz/ Zidovudine/ Lamivudine

Tablet 600mg/300mg/150mg

• Cipla Duovir and Efavirenz Co-Pack (Cipla Medpro)

Zidovudine/ Lamivudine/ Nevirapine

Tablet 300mg/200mg/150mg

• Mivirido (Mylan)
• Triplavar (Cipla Medpro)

Dolutegravir/ Abacavir/ Lamivudine

Tablet 50mg/600mg/300mg

• Trelavue (GSK) originator