Lamivudine

Uses

Lamivudine is used for the treatment of chronic hepatitis B associated with evidence of hepatitis B viral replication and active liver inflammation.

Lamivudine is also used to associated treatment for these conditions: Hepatitis B Chronic Infection, Human Immunodeficiency Virus (HIV) Infections

How Lamivudine works

Lamivudine is a synthetic nucleoside analogue and is phosphorylated intracellularly to its active 5'-triphosphate metabolite, lamivudine triphosphate (L-TP). This nucleoside analogue is incorporated into viral DNA by HIV reverse transcriptase and HBV polymerase, resulting in DNA chain termination.

Dosage

Lamivudine dosage

The recommended oral dose of Lamivudine for the treatment of chronic hepatitis B in adults is 100 mg once daily.

Side Effects

Several serious adverse events reported with lamivudine (lactic acidosis and severe hepatomegaly with steatosis, post treatment exacerbations of hepatitis B, pancreatitis, and emergence of viral mutants associated with reduced drug susceptibility and diminished treatment response). Malaise, fatigue, fever, ENT infections, sore throat, nausea, vomiting, abdominal discomfort, pain, diarrhea, myalgia, arthralgia, headache, skin rashes may occur. Lactic acidosis and severe hepatomegaly with steatosis, have been reported.

Toxicity

The most common reported adverse reactions (incidence ≥15%) in adults were headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough.

Precaution

Patients should be assessed before beginning treatment and during treatment with lamivudine by a physician experienced in the management of chronic hepatitis B.

Interaction

Trimethoprim 160 mg / Sulfamethoxazole 800 mg once daily has been shown to increase lamivudine exposure (AUC). The effect of higher doses of trimethoprim /sulfamethoxazole on lamivudine pharmacokinetics has not been investigated.

Food Interaction

• Take with or without food. Food delays drug absorption, but not to a clinically significant extent.

Lamivudine Cholesterol interaction

[Major] The reverse transcriptase inhibitors, didanosine (ddI), zalcitabine (ddC), stavudine (d4T) and lamivudine (3TC), may cause pancreatitis.

The incidence is generally low but is approximately 7% with ddI, and up to 15% in pediatric patients given 3TC.

Patients with a history of or known risk factors for pancreatitis, such as alcohol abuse or hypertriglyceridemia, should be monitored closely during therapy with these agents.

Therapy should be discontinued at the first signs or symptoms suggestive of pancreatitis (e.g., nausea, vomiting, abdominal pain, hyperamylasemia with dysglycemia, rising triglycerides, decreasing serum calcium), and preferably permanently discontinued if clinical pancreatitis develops.

Lamivudine Drug Interaction

Unknown: rosuvastatin, rosuvastatin, raltegravir, raltegravir, ritonavir, ritonavir, acetaminophen, acetaminophen, dolutegravir, dolutegravir, valproic acid, valproic acid, cyanocobalamin, cyanocobalamin, pyridoxine, pyridoxine, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Lamivudine Disease Interaction

Major: hepatotoxicity, pancreatitis, renal dysfunction

Volume of Distribution

Apparent volume of distribution, IV administration = 1.3 ± 0.4 L/kg. Volume of distribution was independent of dose and did not correlate with body weight.

Elimination Route

Lamivudine was rapidly absorbed after oral administration in HIV-infected patients. Absolute bioavailability in 12 adult patients was 86% ± 16% (mean ± SD) for the 150-mg tablet and 87% ± 13% for the oral solution. The peak serum lamivudine concentration (Cmax) was 1.5 ± 0.5 mcg/mL when an oral dose of 2 mg/kg twice a day was given to HIV-1 patients. When given with food, absorption is slower, compared to the fasted state.

Half Life

5 to 7 hours (healthy or HBV-infected patients)

Clearance

• Renal clearance = 199.7 ± 56.9 mL/min [300 mg oral dose, healthy subjects]
• Renal clearance = 280.4 ± 75.2 mL/min [single IV dose, HIV-1-infected patients]
• Total clearance = 398.5 ± 69.1 mL/min [HIV-1-infected patients]

Elimination Route

The majority of lamivudine is eliminated unchanged in urine by active organic cationic secretion. 5.2% ± 1.4% (mean ± SD) of the dose was excreted as the trans-sulfoxide metabolite in the urine. Lamivudine is excreted in human breast milk and into the milk of lactating rats.

Pregnancy & Breastfeeding use

There is no adequate and well-controlled study in pregnant women. Lamivudine should be used during pregnancy only if the potential benefits outweigh the risks. Although it is not known if lamivudine is excreted in human milk, there is the potential for adverse effects from lamivudine in nursing infants. Mothers should be instructed not to breast feed if they are receiving lamivudine.

Contraindication

Lamivudine is contraindicated in patients hypersensitive to any of the components of the product.

Special Warning

It is recommended that doses of Lamivudine should be adjusted in accordance with renal function. Dosage adjustment of Lamivudine in accordance with creatinine clearance is as follows:

• CrCl 50 ml/min: 100 mg once daily
• CrCl 30-49 ml/min: 100 mg first dose, then 50 mg once daily
• CrCl 15-29 ml/min: 100 mg first dose, then 25 mg once daily
• CrCl 5-14 ml/min: 35 mg first dose, then 15 mg once daily
• CrCl <5 ml/min: 35 mg first dose, then 10 mg once daily

Use in children: Safety and efficacy of lamivudine for the treatment of chronic hepatitis B in children have not been established.

Storage Condition

Store below 30˚C. Protect from light. Keep out of the reach of children.

Innovators Monograph

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