Dosage Form: tablet, film coated and oral solution
FULL PRESCRIBING INFORMATION
Lactic Acidosis and Severe Hepatomegaly: 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. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions (5.1).
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 Epivir. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue Epivir and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.2)].
Important Differences Among Lamivudine-Containing Products: Epivir Tablets and Oral Solution (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 (5.2)
Indications and Usage for Epivir
Epivir is a nucleoside analogue indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection. Limitation of use: The dosage of this product is for HIV-1 and not for HBV.
Epivir Dosage and Administration
Adults and Adolescents >16 years of age
The recommended oral dose of Epivir in HIV-1-infected adults and adolescents >16 years of age is 300 mg daily, administered as either 150 mg twice daily or 300 mg once daily, in combination with other antiretroviral agents. 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 (5.2)].
Pediatric Patients
The recommended oral dose of Epivir Oral Solution in HIV-1-infected pediatric patients 3 months to 16 years of age is 4 mg/kg twice daily (up to a maximum of 150 mg twice a day), administered in combination with other antiretroviral agents.
Epivir is also available as a scored tablet for HIV-1-infected pediatric patients who weigh ≥14 kg and for whom a solid dosage form is appropriate. Before prescribing Epivir Tablets, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow Epivir Tablets, the oral solution formulation should be prescribed. The recommended oral dosage of Epivir Tablets for HIV-1-infected pediatric patients is presented in Table 1.
Weight (kg) | Dosage Regimen Using Scored 150-mg Tablet | Total Daily Dose | |
| AM Dose | PM Dose | ||
| 14 to 21 | ½ tablet (75 mg) | ½ tablet (75 mg) | 150 mg |
| >21 to <30 | ½ tablet (75 mg) | 1 tablet (150 mg) | 225 mg |
| ≥30 | 1 tablet (150 mg) | 1 tablet (150 mg) | 300 mg |
Patients With Renal Impairment
Dosing of Epivir is adjusted in accordance with renal function. Dosage adjustments are listed in Table 2 [see Clinical Pharmacology (12.3)].
| Creatinine Clearance (mL/min) | Recommended Dosage of Epivir |
| ≥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 Epivir is required after routine (4-hour) hemodialysis or peritoneal dialysis.
Although there are insufficient data to recommend a specific dose adjustment of Epivir in pediatric patients with renal impairment, a reduction in the dose and/or an increase in the dosing interval should be considered.
Dosage Forms and Strengths
- Epivir Scored Tablets
150 mg, are white, diamond-shaped, scored, film-coated tablets debossed with “GX CJ7” on both sides.
- Epivir Tablets
300 mg, are gray, modified diamond-shaped, film-coated tablets engraved with “GX EJ7” on one side and plain on the reverse side.
- Epivir Oral Solution
A clear, colorless to pale yellow, strawberry-banana flavored liquid, containing 10 mg of lamivudine per 1 mL.
Contraindications
Epivir Tablets and Oral Solution are contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., anaphylaxis) to any of the components of the products.
Warnings and Precautions
Lactic Acidosis/Severe Hepatomegaly With Steatosis
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. 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 Epivir to any patient with known risk factors for liver disease; however, cases also have been reported in patients with no known risk factors. Treatment with Epivir 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).
Patients With HIV-1 and Hepatitis B Virus Co-infection
Posttreatment Exacerbations of Hepatitis: In clinical trials in non-HIV-1-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 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. There is insufficient evidence to determine whether re-initiation of lamivudine alters the course of posttreatment exacerbations of hepatitis.
Important Differences Among Lamivudine-Containing Products: Epivir Tablets and Oral Solution 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, Epivir Tablets, Epivir Oral Solution, COMBIVIR® (lamivudine/zidovudine) Tablets, EPZICOM® (abacavir sulfate and lamivudine) Tablets, or TRIZIVIR® (abacavir sulfate, lamivudine, and zidovudine) Tablets should be used as part of an appropriate combination regimen.
Emergence of Lamivudine-Resistant HBV: In non–HIV-1-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 (see full prescribing information for Epivir-HBV for additional information). Emergence of hepatitis B virus variants associated with resistance to lamivudine has also been reported in HIV-1-infected patients who have received lamivudine-containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus.
Use With Other Lamivudine- and Emtricitabine-Containing Products
Epivir should not be administered concomitantly with other lamivudine-containing products including Epivir-HBV Tablets, Epivir Oral Solution, COMBIVIR (lamivudine/zidovudine) Tablets, EPZICOM (abacavir sulfate and lamivudine) Tablets, or TRIZIVIR (abacavir sulfate, lamivudine, and zidovudine) or emtricitabine-containing products, including ATRIPLA® (efavirenz, emtricitabine, and tenofovir), EMTRIVA® (emtricitabine), TRUVADA® (emtricitabine and tenofovir), or COMPLERA™ (rilpivirine/emtricitabine/tenofovir).
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-1/HCV virologic suppression) was seen when ribavirin was coadministered with lamivudine in HIV-1/HCV co-infected patients [see Clinical Pharmacology (12.3)], hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin. Patients receiving interferon alfa with or without ribavirin and Epivir should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. Discontinuation of Epivir 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., Child-Pugh >6). See the complete prescribing information for interferon and ribavirin.
Pancreatitis
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, Epivir should be used with caution. Treatment with Epivir should be stopped immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur [see Adverse Reactions (6.1)].
Immune Reconstitution Syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Epivir. 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.
Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment.
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.
Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Lactic acidosis and severe hepatomegaly with steatosis [see Boxed Warning, Warnings and Precautions (5.1)].
- Severe acute exacerbations of hepatitis B [see Boxed Warning, Warnings and Precautions (5.2)].
- Hepatic decompensation in patients co-infected with HIV-1 and hepatitis C [see Warnings and Precautions (5.4)].
- Pancreatitis [see Warnings and Precautions (5.5)].
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adults - Clinical Trials in HIV-1: The safety profile of Epivir in adults is primarily based on 3,568 HIV-1-infected patients in 7 clinical trials.
The most common adverse reactions are headache, nausea, malaise, fatigue, nasal signs and symptoms, diarrhea and cough.
Selected clinical adverse reactions in ≥5% of patients during therapy with Epivir 150 mg twice daily plus RETROVIR® 200 mg 3 times daily for up to 24 weeks are listed in Table 3.
| Adverse Reaction | Epivir 150 mg Twice Daily plus RETROVIR (n = 251) | RETROVIRa (n = 230) |
| Body as a Whole | ||
| Headache | 35% | 27% |
| Malaise & fatigue | 27% | 23% |
| Fever or chills | 10% | 12% |
| Digestive | ||
| Nausea | 33% | 29% |
| Diarrhea | 18% | 22% |
| Nausea & vomiting | 13% | 12% |
| Anorexia and/or decreased appetite | 10% | 7% |
| Abdominal pain | 9% | 11% |
| Abdominal cramps | 6% | 3% |
| Dyspepsia | 5% | 5% |
| Nervous System | ||
| Neuropathy | 12% | 10% |
| Insomnia & other sleep disorders | 11% | 7% |
| Dizziness | 10% | 4% |
| Depressive disorders | 9% | 4% |
| Respiratory | ||
| Nasal signs & symptoms | 20% | 11% |
| Cough | 18% | 13% |
| Skin | ||
| Skin rashes | 9% | 6% |
| Musculoskeletal | ||
| Musculoskeletal pain | 12% | 10% |
| Myalgia | 8% | 6% |
| Arthralgia | 5% | 5% |
| a Either zidovudine monotherapy or zidovudine in combination with zalcitabine. | ||
Pancreatitis: Pancreatitis was observed in 9 out of 2,613 adult patients (0.3%) who received Epivir in controlled clinical trials EPV20001, NUCA3001, NUCB3001, NUCA3002, NUCB3002, and NUCB3007 [see Warnings and Precautions (5.5)].
Epivir 300 mg Once Daily: The types and frequencies of clinical adverse reactions reported in patients receiving Epivir 300 mg once daily or Epivir 150 mg twice daily (in 3-drug combination regimens in EPV20001 and EPV40001) for 48 weeks were similar.
Selected laboratory abnormalities observed during therapy are summarized in Table 4.
Test (Threshold Level) | 24-Week Surrogate Endpoint Studiesa | Clinical Endpoint Studya | ||
Epivir plus RETROVIR | RETROVIRb | Epivir plus Current Therapy | Placebo plus Current Therapyc | |
Absolute neutrophil count (<750/mm3) | 7.2% | 5.4% | 15% | 13% |
Hemoglobin (<8.0 g/dL) | 2.9% | 1.8% | 2.2% | 3.4% |
Platelets (<50,000/mm3) | 0.4% | 1.3% | 2.8% | 3.8% |
ALT (>5.0 x ULN) | 3.7% | 3.6% | 3.8% | 1.9% |
AST (>5.0 x ULN) | 1.7% | 1.8% | 4.0% | 2.1% |
Bilirubin (>2.5 x ULN) | 0.8% | 0.4% | ND | ND |
Amylase (>2.0 x ULN) | 4.2% | 1.5% | 2.2% | 1.1% |
| a The median duration on study was 12 months. | ||||
| b Either zidovudine monotherapy or zidovudine in combination with zalcitabine. | ||||
| c Current therapy was either zidovudine, zidovudine plus didanosine, or zidovudine plus zalcitabine. | ||||
| ULN = Upper limit of normal. | ||||
| ND = Not done. | ||||
The frequencies of selected laboratory abnormalities reported in patients receiving Epivir 300 mg once daily or Epivir 150 mg twice daily (in 3-drug combination regimens in EPV20001 and EPV40001) were similar.
Pediatric Patients – Clinical Trials in HIV-1: Epivir Oral Solution has been studied in 638 pediatric patients 3 months to 18 years of age in 3 clinical trials.
Selected clinical adverse reactions and physical findings with a ≥5% frequency during therapy with Epivir 4 mg/kg twice daily plus RETROVIR 160 mg/m2 3 times daily in therapy-naive (≤56 days of antiretroviral therapy) pediatric patients are listed in Table 5.
Adverse Reaction | Epivir plus RETROVIR (n = 236) | Didanosine (n = 235) |
Body as a Whole | ||
Fever | 25% | 32% |
Digestive | ||
Hepatomegaly | 11% | 11% |
Nausea & vomiting | 8% | 7% |
Diarrhea | 8% | 6% |
Stomatitis | 6% | 12% |
Splenomegaly | 5% | 8% |
Respiratory | ||
Cough | 15% | 18% |
Abnormal breath sounds/wheezing | 7% | 9% |
Ear, Nose, and Throat | ||
Signs or symptoms of earsa | 7% | 6% |
Nasal discharge or congestion | 8% | 11% |
Other | ||
Skin rashes | 12% | 14% |
Lymphadenopathy | 9% | 11% |
| a Includes pain, discharge, erythema, or swelling of an ear. | ||
Pancreatitis: Pancreatitis, which has been fatal in some cases, has been observed in antiretroviral nucleoside-experienced pediatric patients receiving Epivir alone or in combination with other antiretroviral agents. In an open-label dose-escalation study (NUCA2002), 14 patients (14%) developed pancreatitis while receiving monotherapy with Epivir. Three of these patients died of complications of pancreatitis. In a second open-label study (NUCA2005), 12 patients (18%) developed pancreatitis. In Study ACTG300, pancreatitis was not observed in 236 patients randomized to Epivir plus RETROVIR. Pancreatitis was observed in 1 patient in this study who received open-label Epivir in combination with RETROVIR and ritonavir following discontinuation of didanosine monotherapy [see Warnings and Precautions (5.5)].
Paresthesias and Peripheral Neuropathies: Paresthesias and peripheral neuropathies were reported in 15 patients (15%) in Study NUCA2002, 6 patients (9%) in Study NUCA2005, and 2 patients (<1%) in Study ACTG300.
Selected laboratory abnormalities experienced by therapy-naive (≤56 days of antiretroviral therapy) pediatric patients are listed in Table 6.
Test (Threshold Level) | Epivir plus RETROVIR | Didanosine |
Absolute neutrophil count (<400/mm3) | 8% | 3% |
Hemoglobin (<7.0 g/dL) | 4% | 2% |
Platelets (<50,000/mm3) | 1% | 3% |
ALT (>10 x ULN) | 1% | 3% |
AST (>10 x ULN) | 2% | 4% |
Lipase (>2.5 x ULN) | 3% | 3% |
Total Amylase (>2.5 x ULN) | 3% | 3% |
| ULN = Upper limit of normal. | ||
Neonates - Clinical Trials in HIV-1: Limited short-term safety information is available from 2 small, uncontrolled studies in South Africa in neonates receiving lamivudine with or without zidovudine for the first week of life following maternal treatment starting at Week 38 or 36 of gestation [see Clinical Pharmacology (12.3)]. Selected adverse reactions reported in these neonates included increased liver function tests, anemia, diarrhea, electrolyte disturbances, hypoglycemia, jaundice and hepatomegaly, rash, respiratory infections, and sepsis; 3 neonates died (1 from gastroenteritis with acidosis and convulsions, 1 from traumatic injury, and 1 from unknown causes). Two other nonfatal gastroenteritis or diarrhea cases were reported, including 1 with convulsions; 1 infant had transient renal insufficiency associated with dehydration. The absence of control groups limits assessments of causality, but it should be assumed that perinatally exposed infants may be at risk for adverse reactions comparable to those reported in pediatric and adult HIV-1-infected patients treated with lamivudine-containing combination regimens. Long-term effects of in utero and infant lamivudine exposure are not known.
Postmarketing Experience
In addition to adverse reactions reported from clinical trials, the following adverse reactions have been reported during postmarketing use of Epivir. Because these reactions are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to lamivudine.
Body as a Whole: Redistribution/accumulation of body fat [see Warnings and Precautions (5.7)].
Endocrine and Metabolic: Hyperglycemia.
General: Weakness.
Hemic and Lymphatic: Anemia (including pure red cell aplasia and severe anemias progressing on therapy).
Hepatic and Pancreatic: Lactic acidosis and hepatic steatosis, posttreatment exacerbation of hepatitis B [see Boxed Warning, Warnings and Precautions (5.1, 5.2)].
Hypersensitivity: Anaphylaxis, urticaria.
Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis.
Skin: Alopecia, pruritus.
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). No data are available regarding interactions with other drugs that have renal clearance mechanisms similar to that of lamivudine.
Interferon- and Ribavirin-Based Regimens
Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV-1/HCV virologic suppression) was seen when ribavirin was coadministered with lamivudine in HIV-1/HCV co-infected patients, hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin [see Warnings and Precautions (5.4), Clinical Pharmacology (12.3)].
Zalcitabine
Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another. Therefore, use of lamivudine in combination with zalcitabine is not recommended.
Trimethoprim/Sulfamethoxazole (TMP/SMX)
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.
Drugs with No Observed Interactions With Epivir
A drug interaction study showed no clinically significant interaction between Epivir and zidovudine.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category C. There are no adequate and well-controlled studies of Epivir in pregnant women. Animal reproduction studies in rats and rabbits revealed no evidence of teratogenicity. Increased early embryolethality occurred in rabbits at exposure levels similar to those in humans. Epivir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lamivudine pharmacokinetics were studied in pregnant women during 2 clinical studies conducted in South Africa. The study assessed pharmacokinetics in: 16 women at 36 weeks gestation using 150 mg lamivudine twice daily with zidovudine, 10 women at 38 weeks gestation using 150 mg lamivudine twice daily with zidovudine, and 10 women at 38 weeks gestation using lamivudine 300 mg twice daily without other antiretrovirals. These studies were not designed or powered to provide efficacy information. Lamivudine pharmacokinetics in pregnant women were similar to those seen in non-pregnant adults and in postpartum women. Lamivudine concentrations were generally similar in maternal, neonatal, and umbilical cord serum samples. In a subset of subjects, lamivudine amniotic fluid specimens were collected following natural rupture of membranes. Amniotic fluid concentrations of lamivudine were typically 2 times greater than maternal serum levels and 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). It is not known whether risks of adverse events associated with lamivudine are altered in pregnant women compared with other HIV-1-infected patients.
Animal reproduction studies performed at oral doses up to 130 and 60 times the adult dose in rats and rabbits, respectively, revealed no evidence of teratogenicity due to lamivudine. Increased early embryolethality occurred in rabbits at exposure levels similar to those in humans. However, there was no indication of this effect in rats at exposure levels up to 35 times those in humans. Based on animal studies, lamivudine crosses the placenta and is transferred to the fetus [see Nonclinical Toxicology (13.2)].
Antiretroviral Pregnancy Registry: To monitor maternal-fetal outcomes of pregnant women exposed to lamivudine, a Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.
Nursing Mothers
The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. Because of the potential for serious adverse reactions in nursing infants and HIV-1 transmission, mothers should be instructed not to breastfeed if they are receiving lamivudine.
Lamivudine is excreted into human milk. Samples of breast milk obtained from 20 mothers receiving lamivudine monotherapy (300 mg twice daily) or combination therapy (150 mg lamivudine twice daily and 300 mg zidovudine twice daily) had measurable concentrations of lamivudine.
Pediatric Use
The safety and effectiveness of twice-daily Epivir in combination with other antiretroviral agents have been established in pediatric patients 3 months and older [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.2)].
Geriatric Use
Clinical studies of Epivir did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. In particular, because lamivudine is substantially excreted by the kidney and elderly patients are more likely to have decreased renal function, renal function should be monitored and dosage adjustments should be made accordingly [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)].
Patients With Impaired Renal Function
Reduction of the dosage of Epivir is recommended for patients with impaired renal function [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)].
Overdosage
There is no known antidote for Epivir. One case of an adult ingesting 6 g of Epivir was reported; there were no clinical signs or symptoms noted and hematologic tests remained normal. Two cases of pediatric overdose were reported in Study ACTG300. One case involved a single dose of 7 mg/kg of Epivir; the second case involved use of 5 mg/kg of Epivir 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.
Epivir Description
Epivir (also known as 3TC) is a brand name for lamivudine, a synthetic nucleoside analogue with activity against HIV-1 and HBV. The chemical name of lamivudine is (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one. Lamivudine is the (-)enantiomer of a dideoxy analogue of cytidine. Lamivudine has also been referred to as (-)2′,3′-dideoxy, 3′-thiacytidine. It has a molecular formula of C8H11N3O3S and a molecular weight of 229.3. It has the following structural formula:
Lamivudine is a white to off-white crystalline solid with a solubility of approximately 70 mg/mL in water at 20°C.
Epivir Tablets are for oral administration. Each scored 150-mg film-coated tablet contains 150 mg of lamivudine and the inactive ingredients hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, sodium starch glycolate, and titanium dioxide.
Each 300-mg film-coated tablet contains 300 mg of lamivudine and the in
