Lamivudine is a synthetic nucleoside analogue. Intracellularly, lamivudine is phosphorylated to its active 5′-triphosphate metabolite, lamivudine triphosphate, 3TC-TP. Incorporation of the monophosphate form into viral DNA by HBV reverse transcriptase results in DNA chain termination. 3TC-TP also inhibits the RNA and DNA-dependent DNA polymerase activities of HIV-1 reverse transcriptase (RT). 3TC-TP is a weak inhibitor of mammalian DNA polymerases.

Lamivudine was rapidly absorbed after oral administration.

The peak serum lamivudine concentration (Cmax) occurs between 0.5 and 2 hours after administration. Bioavailability is about 86% ± 16%

Binding of lamivudine to human plasma proteins is low (<36%). The majority of lamivudine is eliminated unchanged in urine.

 

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

 

LAMIFIX is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of the products.

 

- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including lamivudine and other antiretrovirals. Obesity and prolonged nucleoside exposure may be risk factors.

Particular caution should be excercised when administering LAMIFIX to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors.

Treatment with LAMIFIX should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transminase elevations).

- When patients dually infected with HBV and HIV are treated with LAMIFIX (the higher dosage indicated for HIV therapy should be used as part of an appropriate combination regimen) and HIV counseling and testing should be offered to all patients before beginning LAMIFIX and periodically during treatment because of the risk of rapid emergence of resistant HIV and limitation of hepatitis B in a patient who has unrecognized or untreated HIV infection or acquires HIV infection during treatment.

- Post treatment exacerbations of hepatitis with clinical and laboratory evidence, or the re-emergence of HBV DNA after stopping treatment, so that patients should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.

 - Pancreatitis has been reported in patients receiving lamivudine, particularly in HIV-infected pediatric patients with prior nucleoside exposure.

 

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

The optimal duration of treatment, the durability of HBeAg seroconversions occurring during treatment, and the relationship between treatment response and long term outcomes such as hepatocellular carcinoma ordecompensated cirrhosis are not known.

- Reduction of the dosage of LAMIFIX is recommended for patients with impaired renal function.

- Testing for HIV periodically before and during therapy to avoid inappropriate therapy and development of resistant HIV is recommended.

- Patients should be informed that deterioration of liver disease has occurred in some cases when treatment was discontinued. Patients should be advised to discuss any changes in regimen with their physician.

- Patients should be informed that emergence of resistant hepatitis B virus and worsening of disease can occur during treatment, and they should promptly report any new symptoms to their physician.

- Patients should be advised that treatment with LAMIFIX has not been shown to reduce the risk of transmission of HBV to others through sexual contact or blood contamination

- Diabetic patients should be advised that each 20-mL dose of LAMIFIX Oral Solution contains 4 grams of sucrose.

 

Lamivudine is predominantly eliminated in the urine by active organic cationic secretion. The possibility of interactions with other drugs administered concurrently should be considered, particularly when their main route of elimination is active renal secretion via the organic cationic transport system (e.g., trimethoprim).

TMP 160 mg/SMX 800 mg once daily has been shown to increase lamivudine exposure (AUC) by 44%. No change in dose of either drug is recommended. There is no information regarding the effect on lamivudine pharmacokinetics of higher doses of TMP/SMX such as those used to treat Pneumocystis carinii pneumonia. No data are available regarding interactions with other drugs that have renal clearance mechanisms similar to that of lamivudine.

Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another. Therefore, use of lamivudine in combination with zalcitabine is not recommended.

 

Pregnancy Category C.

- LAMIFIX should be used during pregnancy only if the potential benefits outweigh the risks.

- LAMIFIX has not been shown to affect the transmission of HBV from mother to infant, and appropriate infant immunizations should be used to prevent neonatal acquisition of HBV.

- Mothers should be instructed not to breastfeed if they are receiving LAMIFIX.

 

Safety and efficacy of LAMIFIX for treatment of chronic hepatitis B in children have been studied in pediatric patients from 2 to 17 years of age, but in pediatric patients <2 years of age have not been established.

 

Dosage adjustments should be made in geriatric patients because lamivudine is substantially excreted by the kidney and elderly patients are more likely to have decreased renal function so renal function should be monitored.

 

The most common adverse effects associated with Lamivudine include abdominal pain, nausea, vomiting, diarrhea, headache, fever, rash, malaise and fatigue, fever and chills, arthralgia, ear nose and throat infection, sore throat, myalgia and skin rashes.

Patients taking lamivudine for the treatment of chronic hepatitis B commonly also have increased serum levels of alanine aminotransferase (ALT).

Pancreatitis has been reported rarely. Neutropenia and increase in liver enzymes and amylase elevation have occurred. Lactic acidosis usually associated with hepatomegaly and steatosis has been reported in the treatment with nucleoside reverse transcriptase inhibitors.

Posttreatment ALT elevations were observed more frequently in patients who had received LAMIFIX than in patients who had received placebo.

Nasal signs and symptoms, dizziness, and pancreatitis.

Most commonly observed adverse events in the pediatric trials were similar to those in adult trials; in addition, respiratory symptoms (cough, bronchitis, and viral respiratory infections).

Pancreatitis was observed in 14% to 15% of patients.

 

Adults: The recommended oral dose of LAMIFIX for treatment of chronic hepatitis B in adults is 100 mg once daily.

The formulation and dosage of lamivudine in LAMIFIX are not appropriate for patients dually infected with HBV and HIV. If lamivudine is administered to such patients, the higher dosage indicated for HIV therapy should be used as part of an appropriate combination regimen.

Pediatric Patients: The recommended oral dose of LAMIFIX for pediatric patients 2 to 17 years of age with chronic hepatitis B is 3 mg/kg once daily up to a maximum daily dose of 100 mg.

- No additional dosing of LAMIFIX is required after routine (4-hour) hemodialysis or peritoneal dialysis.

Although there are insufficient data to recommend a specific dose adjustment of LAMIFIX in pediatric patients with renal impairment, a dose reduction should be considered.

-Safety and effectiveness of treatment of adults and pediatrics beyond 1 year have not been established and the optimum duration of treatment is not known.

 

- LAMIFIX - Film Coated Tablets: A Alu/Alu pack of 10 f.c.tablets. Each f.c.tablet contains 100 mg Lamivudine.

- LAMIFIX – Oral Solution: A pack of glass bottle of 100 mL. Each 1 mL contains 5 mg Lamivudine.

 

Store LAMIFIX - Film Coated Tablets and Oral Solution at temperature between (15-30)°C.