LAMIVUDINE — lamivudine tablet, film coated
Macleods Pharmaceuticals Limited
Exacerbations of Hepatitis B
Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue lamivudine and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.1)].
Important Differences among Lamivudine-Containing Products
Lamivudine tablets (used to treat HIV-1 infection) contain a higher dose of the active ingredient (lamivudine) than EPIVIR-HBV tablets and oral solution (used to treat chronic HBV infection). Patients with HIV-1 infection should receive only dosage forms appropriate for treatment of HIV-1 [see Warnings and Precautions (5.1)].
Lamivudine tablets are nucleoside analogues indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.
Limitations of Use: • The dosage of this product is for HIV-1 and not for HBV.
The recommended dosage of lamivudine in HIV-1-infected adults is 300 mg daily, administered as either 150 mg taken orally twice daily or 300 mg taken orally once daily with or without food. If lamivudine is administered to a patient infected with HIV-1 and HBV, the dosage indicated for HIV-1 therapy should be used as part of an appropriate combination regimen [see Warnings and Precautions (5.1)].
Lamivudine scored tablet is the preferred formulation for HIV-1-infected pediatric patients who weigh at least 14 kg and for whom a solid dosage form is appropriate. Before prescribing lamivudine scored tablets, pediatric patients should be assessed for the ability to swallow tablets. The recommended oral dosage of lamivudine tablets for HIV-1-infected pediatric patients is presented in Table 1.
Table 1. Dosing Recommendations for Lamivudine Scored (150-mg) Tablets in Pediatric Patients
|Weight (kg)||Once-Daily Dosing Regimena||Twice-Daily Dosing Regimen Using Scored 150-mg Tablet|
|AM Dose||PM Dose||Total Daily Dose|
|14 to <20||1 tablet (150 mg)||½ tablet (75 mg)||½ tablet (75 mg)||150 mg|
|≥20 to <25||1½ tablets (225 mg)||½ tablet (75 mg)||1 tablet (150 mg)||225 mg|
|≥25||2 tablets (300mg)b||1 tablet (150 mg)||1 tablet (150 mg)||300 mg|
a Data regarding the efficacy of once-daily dosing is limited to subjects who transitioned from twice-daily dosing to once-daily dosing after 36 weeks of treatment [see Clinical Studies (14.2)].
b Patients may alternatively take one 300-mg tablet, which is not scored.
Dosing of lamivudine is adjusted in accordance with renal function. Dosage adjustments are listed in Table 2 [see Clinical Pharmacology (12.3)].
Table 2. Adjustment of Dosage of Lamivudine in Adults and Adolescents (Greater than or Equal to 25 kg) in Accordance with Creatinine Clearance
|Creatinine Clearance (mL/min)||Recommended Dosage of Lamivudine|
|≥50||150 mg twice daily or 300 mg once daily|
|30-49||150 mg once daily|
|15-29||150 mg first dose, then 100 mg once daily|
|5-14||150 mg first dose, then 50 mg once daily|
|<5||50 mg first dose, then 25 mg once daily|
No additional dosing of lamivudine is required after routine (4-hour) hemodialysis or peritoneal dialysis. Although there are insufficient data to recommend a specific dose adjustment of lamivudine in pediatric patients with renal impairment, a reduction in the dose and/or an increase in the dosing interval should be considered.
• Lamivudine Tablets USP (Scored)
150 mg tablets are white coloured, biconvex, capsule shaped, film-coated tablets, having score on one side and ‘ML 1’ debossed on the other side.
• Lamivudine Tablets USP
300 mg tablets are grey coloured, biconvex, capsule shaped, film-coated tablets, debossed with ‘U27’ on one side and plain on the other side.
Lamivudine tablets are contraindicated in patients with a previous hypersensitivity reaction to lamivudine.
Posttreatment Exacerbations of Hepatitis
Clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of lamivudine. These exacerbations have been detected primarily by serum ALT elevations in addition to re-emergence of HBV DNA. Although most events appear to have been self-limited, fatalities have been reported in some cases. Similar events have been reported from postmarketing experience after changes from lamivudine-containing HIV-1 treatment regimens to non-lamivudine-containing regimens in patients infected with both HIV-1 and HBV. The causal relationship to discontinuation of lamivudine treatment is unknown. Patients should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.
Important Differences among Lamivudine-Containing Products
Lamivudine tablets contain a higher dose of the same active ingredient (lamivudine) than EPIVIR-HBV tablets and EPIVIR-HBV oral solution. EPIVIR-HBV was developed for patients with chronic hepatitis B. The formulation and dosage of lamivudine in EPIVIR-HBV are not appropriate for patients co-infected with HIV-1 and HBV. Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in patients co-infected with HIV-1 and HBV. If treatment with EPIVIR-HBV is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV-1 infection, rapid emergence of HIV-1 resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy HIV-1 treatment. If a decision is made to administer lamivudine to patients co-infected with HIV-1 and HBV, lamivudine tablets, lamivudine oral solution, or another product containing the higher dose of lamivudine should be used as part of an appropriate combination regimen.
Emergence of Lamivudine-Resistant HBV
Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in subjects dually infected with HIV-1 and HBV (see full prescribing information for EPIVIR-HBV). Emergence of hepatitis B virus variants associated with resistance to lamivudine has also been reported in HIV-1-infected subjects who have received lamivudine-containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus.
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