lamivudine

Action and Spectrum

Actions and Spectrum: 

Actions: 

lamivudine is a substituted cytidine analogue or cytosine analogue which is effective against both HIV and HBV in vivo and in vitro. Intracellular phosphorylation of lamivudine to triphosphate that shows action with cytidine triphosphate and interferes with DNA of growing HBV or HIV where it inhibits reverse transcriptase action leading to termination of viral DNA chain. 

Spectrum: 

The spectrum of lamivudine is mainly indicated for the treatment of chronic HBV infection. Whereas for HIV infection it is used with other antiretroviral drugs in which lamivudine is taken as oral solution as well as tablets depending up on the condition of patient clinically. lamivudine is also available in multiple mixture with fixed combinations with other antiretroviral agents.

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Headache (35%) 

Fatigue (25 -27%) 

Malaise (25-27%) 

Paresthesia (15%) 

Peripheral neuropathy (15%) 

Neuropathy (12%) 

Insomnia (11%) 

Sleep disorder (11%) 

Skin rash (9-12%) 

Nausea (33%) 

Diarrhea (14 – 18% adults, 8% children) 

Sore throat (13%) 

Vomiting (13%) 

Hepatomegaly (11 % children) 

Cough (15 – 18 %) 

Fever (25% children) 

1-10% 

Dizziness (10%) 

Chills (10%) 

Depression (9%) 

Increased amylase (2 – 4 %) 

Increased serum lipase (3% children, 10% adults) 

Decreased appetite (10%) 

Anorexia (10%) 

Stomatitis (6% children) 

Dyspepsia (5%) 

Lymphadenopathy (9% children)  

Increased serum aspartate aminotransferase (2-4%) 

Increased creatinine phosphokinase (9%) 

Myalgia (8%) 

Arthralgia (5%) 

Ear disease (7%) 

Wheezing (7%) 

Decreased hemoglobin (2-4%) 

<1%  

Alopecia 

Anaphylaxis 

Anemia 

Asthenia 

Cramps 

Hyperbilirubinemia 

Hyperglycemia 

Lactic acidosis 

Liver steatosis 

Muscle cramps 

Myasthenia 

Pruritus 

Rbc aplasia 

urticaria 

Black Box Warning

Black Box Warning: 

Hepatitis b exacerbations is observed in patients with chronic HBV infection and also with patients who are co infected with HIV-1 up on termination of this drug. Only medicine that are suitable for HIV-1 should be used I the treatment of HIV-1 infected patients.

Chances of HIV -1 resistance in chronic HBV infected patients in which treatment for HIV-1 infection is unrecognized. Counselling and lab tests are recommended before starting of the therapy.

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 
• Neonates below 1 month 
• Breast feeding 

Cautions 

• Allergy 
• Pancreatitis 
• HIV infection 
• Hepatomegaly / Lactic acidosis 
• Immune reconstitution syndrome 
• Renal impairment 
• Hepatic impairment 
• Blood diseases 
• Alcohol 
• Marijuana 
• Diabetes 
• Drug interactions 
• Pregnancy  
• Breastfeeding 

Pregnancy / Lactation

Pregnancy consideration:  

High level transfer across human placenta with lamivudine so counselling with your clinician is required. 

Breastfeeding warnings:  

Presence of lamivudine in breast milk and also in plasma of infants. Recommended to discuss with your clinician before therapy. 

Pregnancy category: 

Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

lamivudine is a negative enantiomer of cytidine which is phosphorylated intracellularly to triphosphate by cellular kinases. It is a nucleoside reverse transcriptase inhibitor which is incorporated into viral DNA resulting in the termination of the chain.  lamivudine is effective actively against HIV and HBV infections.  

Pharmacodynamics: 

lamivudine is a nRTI or substituted cytidine analogue or cytosine analogue which is effective against both HIV and HBV in vivo and in vitro. Intracellular phosphorylation of lamivudine to triphosphate that shows action with cytidine triphosphate and interferes with DNA of growing HBV or HIV where it inhibits reverse transcriptase action leading to termination of viral DNA chain. 

Pharmacokinetics: 

Absorption 

Rapid absorption of lamivudine via oral route where bioavailability is >80% with peak concentrations following administration is 30-90 minutes. It shows linear pharmacokinetics with AUC values corresponding to the dosage magnitude.  

Distribution 

lamivudine has high level plasma transfer across human placenta and is present in breast milk. It crosses Blood-brain barrier with CSF levels of 5-8% and serum levels of 8-16% in both populations with volume of distribution of approx. 1.3 L/kg when given IV. Protein binding is 35%. 

Metabolism 

lamivudine binds to plama protein is 35%. It doesnot undergo metabolism via CYP450 pathway. 

Elimination and Excretion 

About 70% of the drug is eliminated via urine which is found as unchanged. Half-life of lamivudine is 5 to 7 hours in which its metabolite that is triphosphate is having prolonged half-life of about 15.5 hours. 

Adminstartion

Administration: 

Oral tablets should not be crushed or chewed it should only be swallowed. Patients who have problem with oral tablets must administer to them via oral solution. Tablets that are crushed should be added to food or liquid and taken immediately after mixing. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: lamivudine  

Pronounced: la-MI-vyoo-deen 

Why do we use lamivudine? 

It is a nucleoside reverse transcriptase inhibitor and cytosine analogue indicated mainly for chronic HBV infection alone. It is also indicated with other anti-retroviral drugs that are used in the treatment of HIV-1 infection. Main action of lamivudine is to decrease the viral load of hepatitis B in the body.