Lamivudine
Generic: LAMIVUDINE
Basic Information
Manufacturer
Camber Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
6bd6b9da-df69-46db-813e-4e7f3bdecf95
Indications & Usage
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)
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)
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.
Posttreatment transaminase elevations were observed in some subjects followed after cessation of lamivudine tablets (HBV).
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of lamivudine tablets (HBV).
Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to lamivudine.
Blood and Lympatic Anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, splenomegaly, thrombocytopenia.
Digestive Stomatitis.
Endocrine and Metabolic Hyperglycemia.
General Weakness.
Hepatic and Pancreatic Lactic acidosis and steatosis [see Warnings and Precautions ( 5.1)] , posttreatment exacerbations of hepatitis [see Warnings and Precautions ( 5.2)] , pancreatitis.
Hypersensitivity Anaphylaxis, urticaria.
Musculoskeletal Cramps, rhabdomyolysis.
Nervous Paresthesia, peripheral neuropathy.
Respiratory Abnormal breath sounds/wheezing.
Skin Alopecia, pruritus, rash.
• 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.
Posttreatment transaminase elevations were observed in some subjects followed after cessation of lamivudine tablets (HBV).
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of lamivudine tablets (HBV).
Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to lamivudine.
Blood and Lympatic Anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, splenomegaly, thrombocytopenia.
Digestive Stomatitis.
Endocrine and Metabolic Hyperglycemia.
General Weakness.
Hepatic and Pancreatic Lactic acidosis and steatosis [see Warnings and Precautions ( 5.1)] , posttreatment exacerbations of hepatitis [see Warnings and Precautions ( 5.2)] , pancreatitis.
Hypersensitivity Anaphylaxis, urticaria.
Musculoskeletal Cramps, rhabdomyolysis.
Nervous Paresthesia, peripheral neuropathy.
Respiratory Abnormal breath sounds/wheezing.
Skin Alopecia, pruritus, rash.