Lamivudine and Zidovudine
Generic: LAMIVUDINE AND ZIDOVUDINE
Basic Information
Manufacturer
Exelan Pharmaceuticals Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
4cf565c3-bdec-4c18-93c1-cc7fa8331c90
Indications & Usage
1 INDICATIONS AND USAGE Lamivudine and Zidovudine Tablet, USP a combination of two nucleoside analogues, is indicated in combination with other antiretrovirals for the treatment of HIV-1 infection.
Lamivudine and Zidovudine Tablets USP, a combination of two nucleoside analogue reverse transcriptase inhibitors, are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
(1)
Lamivudine and Zidovudine Tablets USP, a combination of two nucleoside analogue reverse transcriptase inhibitors, are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
(1)
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Hematologic toxicity, including neutropenia and anemia [see Boxed Warning , Warnings and Precautions (5.1) ].
Symptomatic myopathy [see Boxed Warning , Warnings and Precautions (5.2) ].
Lactic acidosis and hepatomegaly with steatosis [see Boxed Warning , Warnings and Precautions (5.3) ].
Acute exacerbations of hepatitis B [see Boxed Warning , Warnings and Precautions (5.4) ].
Hepatic decompensation in patients co-infected with HIV-1 and hepatitis C [see Warnings and Precautions (5.6) ].
Exacerbation of anemia in HIV-1/HCV co-infected patients receiving ribavirin and zidovudine [see Warnings and Precautions (5.6) ].
Pancreatitis [see Warnings and Precautions (5.7) ].
Most commonly reported adverse reactions (incidence greater than or equal to 15%) in adult and pediatric HIV-1 clinical studies of combination lamivudine and zidovudine were headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Exelan Pharmaceuticals, Inc., 1-855-295-7455 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Lamivudine Plus Zidovudine Administered As Separate Formulations: In 4 randomized, controlled trials of lamivudine 300 mg per day plus zidovudine 600 mg per day, the following selected adverse reactions and laboratory abnormalities were observed (see Tables 1 and 2).
Table 1.
Selected Clinical Adverse Reactions (≥5% Frequency) in 4 Controlled Clinical Trials With lamivudine 300 mg/day and zidovudine 600 mg/day Adverse Reaction Lamivudine plus Zidovudine (n = 251) Body as a whole Headache 35% Malaise & fatigue 27% Fever or chills 10% Digestive Nausea 33% Diarrhea 18% Nausea & vomiting 13% Anorexia and/or decreased appetite 10% Abdominal pain 9% Abdominal cramps 6% Dyspepsia 5% Nervous system Neuropathy 12% Insomnia & other sleep disorders 11% Dizziness 10% Depressive disorders 9% Respiratory Nasal signs & symptoms 20% Cough 18% Skin Skin rashes 9% Musculoskeletal Musculoskeletal pain 12% Myalgia 8% Arthralgia 5% Pancreatitis was observed in 9 of the 2,613 adult patients (0.3%) who received lamivudine in controlled clinical trials [see Warnings and Precautions (5.7) ].
Selected laboratory abnormalities observed during therapy are listed in Table 2.
Table 2.
Frequencies of Selected Laboratory Abnormalities Among Adults in 4 Controlled Clinical Trials of lamivudine 300 mg/day plus zidovudine 600 mg/day a Test (Abnormal Level) Lamivudine plus Zidovudine % (n) ULN = Upper limit of normal.
ANC = Absolute neutrophil count.
n = Number of patients assessed.
* Frequencies of these laboratory abnormalities were higher in patients with mild laboratory abnormalities at baseline.
Neutropenia (ANC<750/mm 3 ) 7.2% (237) Anemia (Hgb<8 g/dL) 2.9% (241) Thrombocytopenia (platelets<50,000/mm 3 ) 0.4% (240) ALT (>5.0 x ULN) 3.7% (241) AST (>5.0 x ULN) 1.7% (241) Bilirubin (>2.5x ULN) 0.8% (241) Amylase (>2.0 x ULN) 4.2% (72) 6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following reactions have been identified during post-approval use of lamivudine, zidovudine, and/or lamivudine and zidovudine tablet.
Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made.
These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to lamivudine, zidovudine, and/or lamivudine and zidovudine tablet.
Body as a Whole: Redistribution/accumulation of body fat [see Warnings and Precautions (5.9) ].
Cardiovascular: Cardiomyopathy.
Endocrine and Metabolic: Gynecomastia, hyperglycemia.
Gastrointestinal: Oral mucosal pigmentation, stomatitis.
General: Vasculitis, weakness.
Hemic and Lymphatic: Anemia, (including pure red cell aplasia and anemias progressing on therapy), lymphadenopathy, splenomegaly.
Hepatic and Pancreatic: Lactic acidosis and hepatic steatosis, pancreatitis, posttreatment exacerbation of hepatitis B [see Boxed Warning , Warnings and Precautions (5.3) , (5.4) , (5.7) ].
Hypersensitivity: Sensitization reactions (including anaphylaxis), urticaria.
Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis.
Nervous: Paresthesia, peripheral neuropathy, seizures.
Respiratory: Abnormal breath sounds/wheezing.
Skin: Alopecia, erythema multiforme, Stevens-Johnson syndrome.
Symptomatic myopathy [see Boxed Warning , Warnings and Precautions (5.2) ].
Lactic acidosis and hepatomegaly with steatosis [see Boxed Warning , Warnings and Precautions (5.3) ].
Acute exacerbations of hepatitis B [see Boxed Warning , Warnings and Precautions (5.4) ].
Hepatic decompensation in patients co-infected with HIV-1 and hepatitis C [see Warnings and Precautions (5.6) ].
Exacerbation of anemia in HIV-1/HCV co-infected patients receiving ribavirin and zidovudine [see Warnings and Precautions (5.6) ].
Pancreatitis [see Warnings and Precautions (5.7) ].
Most commonly reported adverse reactions (incidence greater than or equal to 15%) in adult and pediatric HIV-1 clinical studies of combination lamivudine and zidovudine were headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Exelan Pharmaceuticals, Inc., 1-855-295-7455 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Lamivudine Plus Zidovudine Administered As Separate Formulations: In 4 randomized, controlled trials of lamivudine 300 mg per day plus zidovudine 600 mg per day, the following selected adverse reactions and laboratory abnormalities were observed (see Tables 1 and 2).
Table 1.
Selected Clinical Adverse Reactions (≥5% Frequency) in 4 Controlled Clinical Trials With lamivudine 300 mg/day and zidovudine 600 mg/day Adverse Reaction Lamivudine plus Zidovudine (n = 251) Body as a whole Headache 35% Malaise & fatigue 27% Fever or chills 10% Digestive Nausea 33% Diarrhea 18% Nausea & vomiting 13% Anorexia and/or decreased appetite 10% Abdominal pain 9% Abdominal cramps 6% Dyspepsia 5% Nervous system Neuropathy 12% Insomnia & other sleep disorders 11% Dizziness 10% Depressive disorders 9% Respiratory Nasal signs & symptoms 20% Cough 18% Skin Skin rashes 9% Musculoskeletal Musculoskeletal pain 12% Myalgia 8% Arthralgia 5% Pancreatitis was observed in 9 of the 2,613 adult patients (0.3%) who received lamivudine in controlled clinical trials [see Warnings and Precautions (5.7) ].
Selected laboratory abnormalities observed during therapy are listed in Table 2.
Table 2.
Frequencies of Selected Laboratory Abnormalities Among Adults in 4 Controlled Clinical Trials of lamivudine 300 mg/day plus zidovudine 600 mg/day a Test (Abnormal Level) Lamivudine plus Zidovudine % (n) ULN = Upper limit of normal.
ANC = Absolute neutrophil count.
n = Number of patients assessed.
* Frequencies of these laboratory abnormalities were higher in patients with mild laboratory abnormalities at baseline.
Neutropenia (ANC<750/mm 3 ) 7.2% (237) Anemia (Hgb<8 g/dL) 2.9% (241) Thrombocytopenia (platelets<50,000/mm 3 ) 0.4% (240) ALT (>5.0 x ULN) 3.7% (241) AST (>5.0 x ULN) 1.7% (241) Bilirubin (>2.5x ULN) 0.8% (241) Amylase (>2.0 x ULN) 4.2% (72) 6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following reactions have been identified during post-approval use of lamivudine, zidovudine, and/or lamivudine and zidovudine tablet.
Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made.
These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to lamivudine, zidovudine, and/or lamivudine and zidovudine tablet.
Body as a Whole: Redistribution/accumulation of body fat [see Warnings and Precautions (5.9) ].
Cardiovascular: Cardiomyopathy.
Endocrine and Metabolic: Gynecomastia, hyperglycemia.
Gastrointestinal: Oral mucosal pigmentation, stomatitis.
General: Vasculitis, weakness.
Hemic and Lymphatic: Anemia, (including pure red cell aplasia and anemias progressing on therapy), lymphadenopathy, splenomegaly.
Hepatic and Pancreatic: Lactic acidosis and hepatic steatosis, pancreatitis, posttreatment exacerbation of hepatitis B [see Boxed Warning , Warnings and Precautions (5.3) , (5.4) , (5.7) ].
Hypersensitivity: Sensitization reactions (including anaphylaxis), urticaria.
Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis.
Nervous: Paresthesia, peripheral neuropathy, seizures.
Respiratory: Abnormal breath sounds/wheezing.
Skin: Alopecia, erythema multiforme, Stevens-Johnson syndrome.