Antiretroviral Presentation

Lamivudine

BY

TEHREEM KHAN
Anti-Retroviral Drugs Classification
NRTIs NNRTIs Protease Fusion Inhibitors
Inhibitors
Zidovudine (AZT)

Lamivudine(3TC)
Lamivudine(3TC)
Emtricitabine(FTC)

Stavudine(d4T)

Didanosine(ddI)

Tenofovir(TDF)

Abacavir(ABV)

Zalcitabine(ddC)
 Lamivudine

• Cytosine nucleoside analogue

• Active against HIV-1, HIV-2 and HBV
• Inhibits HIV reverse transcriptase and HBV DNA Polymerase.
• Has been approved as part of Multidrug regimen for the treatment of HIV in
adults and children
• Also used for HIV post exposure prophylaxis in the alternative regime.
 Mechanism of action

• NRTIs block the RNA dependent DNA polymerase,

reverse transcriptase, from synthesizing cDNA from
viral RNA.
• Intracellular phosphorylation to the triphosphate
forms
• competition with the natural substrate nucleoside
triphosphate and binding to the extending cDNA
causing chain termination.

Image source : Drugs for HIV infection,

Infectious diseases.
www. sciencedirect.com
 Pharmacology

• Absorption: Rapid
• Oral bioavailability ~ 80%
• Protein bound :<36%
• Elimination half life: 5-7 hours (Adults)
~2 hours(children)
• Excretion: Primarily unchanged in urine
Indications
• Used in combination with other ARTs for treatment of HIV
Co-formulations
ABACAVIR + LAMIVUDINE
•abacavir 600 mg + lamivudine 300 mg tablet, 30

ABACAVIR + LAMIVUDINE + ZIDOVUDINE

•abacavir 300 mg + lamivudine 150 mg + zidovudine 300 mg tablet, 60

DOLUTEGRAVIR + ABACAVIR + LAMIVUDINE

•dolutegravir 50 mg + abacavir 600 mg + lamivudine 300 mg tablet, 30

LAMIVUDINE + ZIDOVUDINE
•lamivudine 150 mg + zidovudine 300 mg tablet, 60
 Adverse effects
• Most favourable toxicity profile
• Common to other ARTs: Nausea, vomiting ,Headache, malaise, fatigue,
• Common to all NRTIs: Pancreatitis, Peripheral neuropathy, lactic acidosis,
lipodystrophy, immune reconstitution syndrome
Specific to Lamivudine
• Severe acute exacerbation of HBV in HIV-HBV c0-infected pts on
discontinuation of drug.
• Emergence of resistance
• Hepatic decompensation (some fatal) reported in HIV-1/HCV co-infected
patients receiving interferon and ribavirin-based regimens
Resistance and cross-resistance
Dosage in Special Circumstances

• The dose of lamivudine should be modified in patients with renal impairment.

• No dose adjustment is necessary in patients with hepatic impairment, although
the safety and efficacy have not been established in patients with decompensated
liver disease.
• Lamivudine is pregnancy category C.
 Relevant studies

• ARROW Trial
• Pediatric subjects who received lamivudine oral solution concomitantly with other
antiretroviral oral solutions at any time in the ARROW trial had

• lower rates of virologic suppression

• lower plasma lamivudine exposure

• developed viral resistance more frequently than those receiving lamivudine tablets

• Recommendation: lamivudine scored tablet is the preferred formulation for HIV-1-

infected pediatric patients who weigh at least 14 kg

• more frequent monitoring of HIV-1 viral load when treating with lamivudine oral
solution.
Summary
• Lamivudine is an NRTI used with other ARTs as first line treatment for HIV
• Various co-formulations available
• Most favorable toxicity profile among all NRTIs
• Dose adjustment necessary in renal impairment
• Don’t use with emtricitabine
 References:
• Starting Antiretroviral treatment for HIV. Available from: https://www.avert.org/living-with-hiv/starting-treatment. [Accessed:
31/8/2017].

• WHO (2015) 'Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV‘

• Public Health England (2016), HIV in the UK

• Evans-Jones JG., et al, (2010) ‘Recognition of risk of clinically significant drug interactions among HIV-infected patients receiving
antiretroviral therapy’, Clinical Infectious Diseases, 50: 1419-21

• Koczor, C. A. and W. Lewis (2010). "Nucleoside reverse transcriptase inhibitor toxicity and mitochondrial DNA." Expert Opin Drug Metab
Toxicol 6(12): 1493-1504.

• Eckhardt, B. J. and R. M. Gulick (2017). 152 - Drugs for HIV Infection A2 - Cohen, Jonathan. Infectious Diseases (Fourth Edition). W. G.
Powderly and S. M. Opal, Elsevier: 1293-1308.e1292.

• The Pharmaceutical Benefits Scheme, Australian Government Department of Health . Lamivudine. Available from:
http://www.pbs.gov.au/pbs/search?term=lamivudine. [Accessed: 31/8/2017].
Thank You