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.
Adults With Impaired Hepatic Function
No dose adjustment for lamivudine is required for patients with impaired hepatic function.

CONTRAINDICATIONS
LAMIVIR Tablets and Oral Solution are contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of the product.

WARNINGS AND PRECAUTIONS
In pediatric patients with a history of prior antiretroviral nucleoside exposure, a history of pancreatitis, or other significant risk factors for the development of pancreatitis, lamivudine should be used with caution. Treatment with lamivudine should be stopped immediately if clinical signs, symptoms or laboratory abnormalities suggestive of pancreatitis occur (see UNDESIRABLE EFFECTS ).

Lactic Acidosis/Severe Hepatomegaly With Steatosis
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of antiretroviral nucleoside analogues alone or in combination, including lamivudine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering lamivudine 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 lamivudine 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 transaminase elevations).

Important Differences Among Lamivudine-Containing Products
LAMIVIR Tablets and Oral Solution contain a higher dose of the same active ingredient (lamivudine) than in LAMIVIR-HBV Tablets. LAMIVIR-HBV was developed for patients with chronic hepatitis B. The formulation and dosage of lamivudine in LAMIVIR-HBV are not appropriate for patients dually infected with HIV and HBV. Lamivudine has not been adequately studied for treatment of chronic hepatitis B in patients dually infected with HIV and HBV. If treatment with LAMIVIR-HBV is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV infection, rapid emergence of HIV resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy HIV treatment. If a decision is made to administer lamivudine to patients dually infected with HIV and HBV, LAMIVIR Tablets, LAMIVIR Oral Solution, or Duovir Tablets should be used as part of an appropriate combination regimen. Duovir (a fixed-dose combination tablet of lamivudine and zidovudine) should not be administered concomitantly with LAMIVIR, LAMIVIR-HBV or Zidovir .

Post- treatment Exacerbations of Hepatitis
In clinical trials in non-HIV-infected patients treated with lamivudine for chronic hepatitis B, 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 post-marketing experience after changes from lamivudine-containing HIV treatment regimens to non-lamivudine-containing regimens in patients infected with both HIV 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. There is insufficient evidence to determine whether re-initiation of lamivudine alters the course of post-treatment exacerbations of hepatitis.

Use With Interferon- and Ribavirin-Based Regimens
In vitro studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues such as lamivudine. Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV/HCV virologic suppression) was seen when ribavirin was co-administered with lamivudine in HIV/HCV co-infected patients, hepatic decompensation (some fatal) has occurred in HIV/HCV co-infected patients receiving combination antiretroviral therapy for HIV and interferon alfa with or without ribavirin. Patients receiving interferon alfa with or without ribavirin and lamivudine should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. Discontinuation of lamivudine should be considered as medically appropriate. Dose reduction or discontinuation of interferon alfa, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Childs Pugh >6) (see the complete prescribing information for interferon and ribavirin).

Patients With HIV and Hepatitis B Virus Co-infection
Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in patients dually infected with HIV and HBV.
In non-HIV-infected patients treated with lamivudine for chronic hepatitis B, emergence of lamivudine-resistant HBV has been detected and has been associated with diminished treatment response. Emergence of hepatitis B virus variants associated with resistance to lamivudine has also been reported in HIV-infected patients who have received lamivudine-containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus. Post-treatment exacerbations of hepatitis have also been reported.

Immune Reconstitution Syndrome:
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including lamivudine. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Differences Between Dosing Regimens:
Trough levels of lamivudine in plasma and of intracellular lamivudine triphosphate were lower with once-daily dosing than with twice-daily dosing. The clinical significance of this observation is not known.

Fat Redistribution
Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance”, have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established .

Drug Interactions
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).
Trimethoprim 160 mg and sulfamethoxazole 800 mg (TMP/SMX) once daily has been shown to increase lamivudine exposure (AUC) by 43%. 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 PCP. 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.

Renal Impairment
Reduction of the dose of lamivudine is recommended for patients with impaired renal function (see DOSAGE AND ADMINISTRATION ).

Pregnancy
Pregnancy Category C. In two clinical studies conducted in South Africa, pharmacokinetic measurements were performed on samples from pregnant women who received lamivudine beginning at Week 38 of gestation (10 women who received 150 mg twice daily in combination with zidovudine and 10 who received lamivudine 300 mg twice daily without other antiretrovirals) or beginning at Week 36 of gestation (16 women who received lamivudine 150 mg twice daily in combination with zidovudine). These studies were not designed or powered to provide efficacy information. Lamivudine pharmacokinetics in the pregnant women were similar to those obtained following birth and in non-pregnant adults. Lamivudine concentrations were generally similar in maternal, neonatal, and cord serum samples. In a subset of subjects from whom amniotic fluid specimens were obtained following natural rupture of membranes, amniotic fluid concentrations of lamivudine ranged from 1.2 to 2.5 mcg/mL (150 mg twice daily) and 2.1 to 5.2 mcg/mL (300 mg twice daily) and were typically greater than 2 times the maternal serum levels. See the “UNDESIRABLE EFFECTS ” section for the limited late-pregnancy safety information available from these studies. Lamivudine should be used during pregnancy only if the potential benefits outweigh the risks.

Lactation
It is recommended that HIV-infected mothers do not breastfeed their infants to avoid risking post-natal transmission of HIV infection. Lamivudine is excreted in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast feed if they are receiving lamivudine.

Pediatric Use
The safety and effectiveness of twice-daily lamivudine in combination with other antiretroviral agents have been established in pediatric patients 3 months of age and older.

UNDESIRABLE EFFECTS
Body as a Whole: Redistribution/accumulation of body fat
Digestive : Stomatitis.
Endocrine and Metabolic: Hyperglycemia.

General: Weakness.
Hemic and Lymphatic: Anemia (including pure red cell aplasia and severe anemia progressing on therapy), lymphadenopathy, splenomegaly.
Hepatic and Pancreatic : Lactic acidosis and hepatic steatosis, pancreatitis, post-treatment exacerbation of hepatitis B (see WARNINGS AND PRECAUTIONS ).
Hypersensitivity: Anaphylaxis, urticaria.
Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis.
Nervous: Paresthesia, peripheral neuropathy.
Respiratory: Abnormal breath sounds/wheezing.
Skin: Alopecia, rash, pruritus.

OVERDOSAGE
There is no known antidote for lamivudine. One case of an adult ingesting 6 g of lamivudine was reported; there were no clinical signs or symptoms noted and hematological tests remained normal. Two cases of pediatric overdose have been reported. One case was a single dose of 7 mg/kg of lamivudine; the second case involved use of 5 mg/kg of lamivudine twice daily for 30 days. There were no clinical signs or symptoms noted in either case. Because a negligible amount of lamivudine was removed via 4-hour hemodialysis, continuous ambulatory peritoneal dialysis, and automated peritoneal dialysis, it is not known if continuous hemodialysis would provide clinical benefit in a lamivudine overdose event. If overdose occurs, the patient should be monitored, and standard supportive treatment applied as required.

PRESENTATION
LAMIVIR -150 Tablets Blister pack of 10 tablets
LAMIVIR Oral Solution Bottle of 100 ml with syringe