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Lamivudine

FDA Drug Information • Also known as: Epivir, Lamivudine

Brand Names
Epivir, Lamivudine
Dosage Form
POWDER
Product Type
BULK INGREDIENT

⚠ Boxed Warning (Black Box)

BOXED WARNING WA RN ING: LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, EXACERBATIONS OF HEPATITIS B, and RISK OF HIV-1 RESISTANCE IF LAMIVUDINE TABLETS (HBV) IS USED IN PATIENTS WITH UNRECOGNIZED OR UNTREATED HIV-1 Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Discontinue lamivudine tablets (HBV) if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions ( 5.1 )] . Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy (including lamivudine tablets (HBV)). Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions ( 5.2 )]. Lamivudine tablets (HBV) are not approved for the treatment of HIV-1 infection because the lamivudine dosage in lamivudine tablets (HBV) is subtherapeutic and monotherapy is inappropriate for the treatment of HIV-1 infection. HIV-1 resistance may emerge in chronic hepatitis B-infected patients with unrecognized or untreated HIV-1 infection.HIV Counseling and testing should be offered to all patients before beginning treatment with lamivudine tablets (HBV) and periodically during treatment [see Warnings and Precautions ( 5.3)] WARNING: LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, EXACERBATIONS OF HEPATITIS B, and RISK OF HIV-1 RESISTANCE IF LAMIVUDINE TABLETS (HBV) IS USED IN PATIENTS WITH UNRECOGNIZED OR UNTREATED HIV-1 INFECTION See full prescribing information for complete boxed warning

  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues. ( 5.1 )
  • Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy (including lamivudine tablets (HBV) Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment. ( 5.2)
  • Lamivudine tablets (HBV) contain a lower dose of the same active ingredient (lamivudine) as lamivudine tablets and oral solution used to treat HIV-1 infection. HIV-1 resistance may emerge in chronic hepatitis B patients with unrecognized or untreated HIV­1 infection because the lamivudine dosage in lamivudine tablets (HBV) is subtherapeutic and monotherapy is inappropriate for the treatment of HIV-1 infection. HIV counseling and testing should be offered to all patients before beginning treatment with lamivudine tablets (HBV) and periodically during treatment. ( 5.3 )

    • Description

    11 DESCRIPTION Lamivudine tablet (HBV) is a synthetic nucleoside analogue with activity against HBV. The chemical name of lamivudine, USP is 2(1H) - Pyrimidinone, 4-amino-1- [2- (hydroxymethyl)-1,3-oxathio-lan-5-yl], (2R-cis)-.It has a molecular formula of C 8 H 11 N 3 O 3 S and a molecular weight of 229.26. It has the following structural formula: Lamivudine USP is a white to an off white solid and soluble in water. Lamivudine Tablets (HBV) are for oral administration. Each tablet contains 100 mg of lamivudine, USP and the inactive ingredients crospovidone, isomalt, isopropyl alcohol, magnesium stearate and methylene chloride. The tablets are coated with Opadry Pink containing hypromellose, iron oxide red, polyethylene glycol, polysorbate 80, titanium dioxide and yellow iron oxide. structure.jpg

    What Is Lamivudine Used For?

    1 INDICATIONS & USAGE Lamivudine tablets (HBV) are indicated for the treatment of chronic hepatitis B virus (HBV) infection associated with evidence of hepatitis B viral replication and active liver inflammation [see Clinical Studies ( 14.1 , 14.2 )] . The following points should be considered when initiating therapy with lamivudine tablets (HBV): Due to high rates of resistance development in treated patients, initiation of treatment with lamivudine tablets (HBV) should only be considered when the use of an alternative antiviral agent with a higher genetic barrier to resistance is not available or appropriate. Lamivudine tablets (HBV) have not been evaluated in patients co-infected with HIV, hepatitis C virus (HCV), or hepatitis delta virus. Lamivudine tablets (HBV) have not been evaluated in liver transplant recipients or in patients with chronic hepatitis B virus infection with decompensated liver disease.

  • Lamivudine tablets (HBV) are a nucleoside analogue reverse transcriptase inhibitor indicated for the treatment of chronic hepatitis B virus infection associated with evidence of hepatitis B viral replication and active liver inflammation. (1)

    • Dosage and Administration

    2 DOSAGE & ADMINISTRATION

  • Adults: 100 mg, once daily. ( 2.2 )
  • Pediatric Patients aged 2 to 17 years: 3 mg per kg once daily up to 100 mg once daily. Prescribe oral solution for pediatric patients requiring less than 100 mg daily. ( 2.3)
  • Patients with Renal Impairment: Doses of lamivudine tablets (HBV) must be adjusted in accordance with renal function. ( 2.4 )
  • Lamivudine tablets (HBV) should not be used with other medications that contain lamivudine or emtricitabine. ( 2.5) 2.1 HIV Counseling and Testing HIV counseling and testing should be offered to all patients before beginning treatment with lamivudine tablets (HBV) and periodically during treatment because of the risk of emergence of resistant-HIV-1 and limitation of treatment options if lamivudine tablets (HBV) is prescribed to treat chronic hepatitis B infection in a patient who has unrecognized HIV-1 infection or acquires HIV-1 infection during treatment [see Warnings and Precautions ( 5.3 )] . 2.2 Recommended Dosage for Adult Patients The recommended oral dosage of lamivudine tablets (HBV) is 100 mg once daily. 2.3 Recommended Dosage for Pediatric Patients The recommended oral dosage of lamivudine tablets (HBV) for pediatric patients aged 2 to 17 years is 3 mg per kg once daily up to a maximum daily dosage of 100 mg. The oral solution formulation should be prescribed for patients requiring a dosage less than 100 mg or if unable to swallow tablets. 2.4 Patients with Renal Impairment Dosage recommendations for adult patients with reduced renal function are provided in Table 1 [see Clinical Pharmacology ( 12.3 )] . Table 1. Dosage of Lamivudine Tablets (HBV) in Adult Patients with Renal Impairment Cre atinine Clearance ( m L/min) Rec o mme nded Dosage of Lamivudine Tablets (HBV) ≥50 100 mg once daily 30-49 100 mg first dose, then 50 mg once daily 15-29 100 mg first dose, then 25 mg once daily 5-14 35 mg first dose, then 15 mg once daily <5 35 mg first dose, then 10 mg once daily Following correction of the dosage for renal impairment, no additional dosage modification of lamivudine tablets (HBV) is required after routine (4-hour) hemodialysis or peritoneal dialysis [see Clinical Pharmacology ( 12.3) ] . There are insufficient data to recommend a specific dosage of lamivudine tablets (HBV) in pediatric patients with renal impairment. 2.5 Important Administration Instructions
  • Lamivudine tablets (HBV) may be administered with or without food.
  • The tablets and oral solution may be used interchangeably [see Clinical Pharmacology ( 12.3)].
  • The oral solution should be used for doses less than 100 mg.
  • Lamivudine tablets (HBV) should not be used with other medications that contain lamivudine or medications that contain emtricitabine 2.6 Assessing Patients during Treatment Patients should be monitored regularly during treatment by a physician experienced in the management of chronic hepatitis B. During treatment, combinations of events such as return of persistently elevated ALT,...

    • Side Effects (Adverse Reactions)

    6 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 Warnings and Precautions ( 5.1 )].
  • Exacerbations of hepatitis B after discontinuation of treatment [see Warnings and Precautions ( 5.2 )].
  • Risk of emergence of resistant HIV-1 infection [see Warnings and Precautions ( 5.3 )].
  • Risk of emergence of resistant HBV infection [see Warnings and Precautions ( 5.4 )].
  • The most common reported adverse reactions in those receiving lamivudine tablets (HBV) (incidence greater than or equal to 10% and reported at a rate greater than placebo) were ear, nose and throat infections, sore throat, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Clinical Trials Experience in of Adult Subjects with Chronic HBV Infection Clinical adverse reactions (regardless of investigator’s causality assessment) reported in greater than or equal to 10% of subjects who received lamivudine tablets (HBV) and reported at a rate greater than in subjects who received placebo are listed in Table 2. Table 2. Clinical Adverse Reactions a Reported in Greater than or Equal to 10% of Subjects who Received Lamivudine Tablets (HBV) for 52 to 68 Weeks and at an Incidence Greater than Placebo (Trials 1 to 3) Adverse Event Lamivudine Tablets (HBV) (n = 332) P lacebo ( n = 200) Ear, Nose, and Throat Ear, nose, and throat infections 25% 21% Sore throat 13% 8% G astrointestinal Diarrhea 14% 12% a Includes adverse events regardless of severity and causality assessment. Specified laboratory abnormalities reported in subjects who received lamivudine tablets (HBV) and reported at a rate greater than in subjects who received placebo are listed in Table 3. Table 3. Frequencies of Specified Laboratory Abnormalities Reported during Treatment at a Greater Frequency in Subjects Treated with Lamivudine Tablets (HBV) than with Placebo (Trials 1 to 3) a Test(Abnormal Level) Subjects with Abnormality/Subjects with Observations Lamivudine Tablets (HBV) Placebo Serum Lipase ≥2.5 x ULN b 10% 7% CPK ≥7 x baseline 9% 5% Platelets <50,000/mm 3 4% 3% a Includes subjects treated for 52 to 68 weeks. b Includes observations during and after treatment in the 2 placebo-controlled trials that collected this information. ULN = Upper limit of normal. In subjects followed for up to 16 weeks after discontinuation of treatment, posttreatment ALT elevations were observed more frequently in subjects who had received lamivudine tablets (HBV) than in subjects who had received placebo. A comparison of ALT elevations between Weeks 52 and 68 in subjects who discontinued lamivudine tablets (HBV) at Week 52 and subjects in the same trials who received placebo throughout the treatment course is shown in Table 4. Table 4. Posttreatment ALT Elevations with No-Active-Treatment Follow-up (Trials 1 and 3) Abnormal Value Subjects with ALT Elevation/ Subjects with Observations a Lamivudine Tablets (HBV) b P lacebo b ALT ≥2 x baseline value 27% 19% ALT ≥3 x baseline value c 21% 8% ALT ≥2 x baseline value and absolute ALT >500 IU/L 15% 7% ALT ≥2 x baseline value; and bilirubin >2 x ULN and ≥2 x baseline value 0.7% 0.9% a Each subject may be represented in one or more category. b During treatment phase. c Comparable to a Grade 3 toxicity in accordance with modified WHO criteria. ULN = Upper limit of normal. Clinical Trials Experience in Pediatric Subjects with Chronic HBV Infection Most commonly observed adverse reactions in the pediatric trials were similar to those in adult trials....

    • Drug Interactions

    7 DRUG INTERACTIONS Sorbitol: Coadministration of lamivudine and sorbitol may result in decreased lamivudine concentrations; when possible, avoid chronic coadministration. Consider more frequent monitoring of HBV viral load when chronic coadministration cannot be avoided. (7.2) 7.1 Drugs Inhibiting Organic Cation Transporters 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) [see Clinical Pharmacology (12.3)]. No data are available regarding interactions with other drugs that have renal clearance mechanisms similar to that of lamivudine. 7.2 Sorbitol Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol-containing medicines with lamivudine [see Clinical Pharmacology (12.3]. Consider more frequent monitoring of HBV viral load when chronic coadministration cannot be avoided.

    Contraindications

    4 CONTRAINDICATIONS Lamivudine tablets (HBV) are contraindicated in patients with a previous hypersensitivity reaction to lamivudine. Lamivudine tablets (HBV) is contraindicated in patients with previous hypersensitivity reaction to lamivudine. (4)

    Pregnancy and Breastfeeding

    8.1 Pregnancy Teratogenic Effects: Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to lamivudine during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from the APR show no substantial difference in the risk of overall major birth defects for lamivudine compared with the background rate for major birth defects of 2.7% reported in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). The APR uses the MACDP as a U.S. reference population for birth defects in the general population. The MACDP evaluates women and infants from a limited geographic area and does not include outcomes for births that occur at less than 20 weeks gestation. Of over 11,000 women exposed to lamivudine in the APR, less than 1% were treated for HBV. The majority of women exposed to lamivudine in the APR were HIV-1-infected and were treated with higher doses of lamivudine compared with HBV mono-infected women. In addition to lamivudine, HIV-1-infected women were also treated with other concomitant medications for HIV-1 infection [see Data]. The estimated rate of miscarriage for women exposed to lamivudine in the indicated population is unknown. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%. Oral administration of lamivudine to pregnant rabbits during organogenesis resulted in embryolethality at systemic exposure (AUC) similar to the recommended clinical dose; however, no adverse developmental effects were observed with oral administration of lamivudine to pregnant rats during organogenesis at plasma concentrations (C max ) 60 times the recommended clinical dose [see Data]. Data Human Data : Based on prospective reports from the APR of over 11,000 exposures to lamivudine (including over...

    Overdosage

    10 OVERDOSAGE There is no known specific treatment for overdose with lamivudine tablets (HBV). If overdose occurs, the patient should be monitored, and standard supportive treatment applied, as required. 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.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING Lamivudine tablets (HBV), 100 mg are pink colored, capsule shaped, biconvex, film coated tablets, debossed with ‘37’ on one side and ‘I’ on the other side. Bottle of 60 tablets NDC 31722--752-60 Bottle of 600 tablets NDC 31722--752-06 Blister card of 10 Unit-dose tablets NDC 31722--752-31 Blister pack of 100 (10x10) Unit-dose tablets NDC 31722--752-32 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Preserve in well-closed, light-resistant containers.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.