Epivir Side Effects
Generic Name: lamivudine
Please note - some side effects for Epivir may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
Side Effects of Epivir - for the Consumer
Epivir
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Epivir:
Seek medical attention right away if any of these SEVERE side effects occur when using Epivir:Cough; diarrhea; dizziness; general body discomfort; headache; loss of appetite; mild mouth pain or swelling; muscle or joint pain; nausea; runny/stuffy nose; stomach pain or cramps; tiredness; trouble sleeping; vomiting.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); burning, numbness, or tingling sensation; dark urine; ear pain or discharge; fever, chills, or sore throat; mental or mood changes; pale stools; persistent loss of appetite; severe or persistent muscle pain, ache, or tenderness; severe or persistent nausea, vomiting, or diarrhea; severe or persistent stomach pain or tenderness; swollen lymph nodes; symptoms of lactic acidosis (eg, fast or difficult breathing; fast, slow, or irregular heartbeat; severe or persistent weakness or tiredness; unusual drowsiness, dizziness, or lightheadedness; unusual feeling of cold in the arms or legs; wheezing); yellowing of the skin or eyes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
Epivir-HBV
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Epivir-HBV:
Seek medical attention right away if any of these SEVERE side effects occur when using Epivir-HBV:Changes in body fat; chills; coughing; decreased appetite; diarrhea; difficulty sleeping; dizziness; ear, nose, and throat infection; general body discomfort; headache; indigestion; joint pain; muscle pain; nausea; sinus drainage; sore throat; stomach discomfort; tiredness.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); dark urine; depression (mental or mood changes); enlarged stomach; increased heart rate; numbness or tingling in the arms or legs; persistent sore throat, chills, or fever; severe muscle or joint pain; stomach tenderness or pain; unusual bleeding or bruising; unusual weakness or exhaustion; vomiting; yellowing of the skin or eyes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
Epivir-HBV Solution
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Epivir-HBV Solution:
Seek medical attention right away if any of these SEVERE side effects occur when using Epivir-HBV Solution:Changes in body fat; chills; coughing; decreased appetite; diarrhea; difficulty sleeping; dizziness; ear, nose, and throat infection; general body discomfort; headache; indigestion; joint pain; muscle pain; nausea; sinus drainage; sore throat; stomach discomfort; tiredness.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); dark urine; depression (mental or mood changes); enlarged stomach; increased heart rate; numbness or tingling in the arms or legs; persistent sore throat, chills, or fever; severe muscle or joint pain; stomach tenderness or pain; unusual bleeding or bruising; unusual weakness or exhaustion; vomiting; yellowing of the skin or eyes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
Epivir Solution
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Epivir Solution:
Seek medical attention right away if any of these SEVERE side effects occur when using Epivir Solution:Cough; diarrhea; dizziness; general body discomfort; headache; loss of appetite; mild mouth pain or swelling; muscle or joint pain; nausea; runny/stuffy nose; stomach pain or cramps; tiredness; trouble sleeping; vomiting.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); burning, numbness, or tingling sensation; dark urine; ear pain or discharge; fever, chills, or sore throat; mental or mood changes; pale stools; persistent loss of appetite; severe or persistent muscle pain, ache, or tenderness; severe or persistent nausea, vomiting, or diarrhea; severe or persistent stomach pain or tenderness; swollen lymph nodes; symptoms of lactic acidosis (eg, fast or difficult breathing; fast, slow, or irregular heartbeat; severe or persistent weakness or tiredness; unusual drowsiness, dizziness, or lightheadedness; unusual feeling of cold in the arms or legs; wheezing); yellowing of the skin or eyes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
TopEpivir Side Effects - for the Professional
Epivir
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.
TopSide Effects by Body System - for Healthcare Professionals
General
The most common side effects reported with lamivudine have included headache, nausea, malaise, fatigue, nasal signs and symptoms, diarrhea, and cough. During clinical studies, HIV-1-infected patients received lamivudine plus zidovudine. Patients with hepatitis B received lamivudine monotherapy.
The adverse effects of lamivudine are sometimes difficult to distinguish from the symptomatology observed during the clinical course of AIDS, as well as from the possible adverse effects of other drugs used in the treatment of HIV-1 infection. Many of the side effects associated with nucleoside reverse transcriptase inhibitor therapy (myopathy, pancreatitis, liver failure, lactic acidosis, etc.) are attributable to their direct toxic effect on mitochondria which causes decreased mitochondrial energy generating capacity.
Nervous system
Nervous system side effects have included headache (up to 35%), neuropathy (12%), insomnia and other sleep disorders (11%), and dizziness (10%). Peripheral neuropathy and paresthesia have been reported during postmarketing experience.
Gastrointestinal
Gastrointestinal side effects have included nausea (33%), diarrhea (up to 18%), abdominal discomfort and pain (16%), nausea and vomiting (up to 15%), anorexia and/or decreased appetite (10%), abdominal pain (9%), abdominal cramps (6%), and dyspepsia (5%). Oral ulcerations and lesions have been observed. Pancreatitis has been rarely reported in adults (less than 0.5%), but may be more common in pediatric patients (up to 18% in 2 limited studies). Pancreatitis and stomatitis have been reported during postmarketing experience.
Hepatic
Hepatic side effects have included elevated ALT (greater than 3 times ULN: 11%; greater than 5 times ULN: up to 3.8%), AST (greater than 5 times ULN; up to 4%), and bilirubin (greater than 2.5 times ULN; up to 0.8%). Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of lamivudine and other nucleoside analogs alone or in combination with other antiretroviral agents. Severe acute exacerbations of hepatitis B, including fatalities, have been reported in patients with HBV (including those coinfected with HIV-1) who have discontinued lamivudine. The causal relationship to stopping lamivudine treatment is unknown. Hepatic decompensation (some fatal) has been reported in patients coinfected with HIV-1 and hepatitis C receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin. Lactic acidosis and hepatic steatosis and posttreatment exacerbation of hepatitis B have been reported during postmarketing experience.
Other
Other side effects have included malaise and fatigue (up to 27%); ear, nose, and throat infections (25%); sore throat (13%); and fever or chills (up to 10%). Weakness has been reported during postmarketing experience.
Respiratory
Respiratory side effects have included nasal signs and symptoms (20%) and cough (18%). Abnormal breath sounds/wheezing have been reported during postmarketing experience.
Hematologic
Hematologic side effects have included decreased absolute neutrophil count (less than 750/mm3; up to 15%), platelets (less than 50,000/mm3; up to 4%), and hemoglobin (less than 8 g/dL; up to 2.9%). Anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, and splenomegaly have been reported during postmarketing experience.
Musculoskeletal
Musculoskeletal side effects have included myalgia (up to 14%), musculoskeletal pain (12%), increased creatine phosphokinase (greater than or equal to 7 times baseline; 9%), and arthralgia (up to 7%). Muscle weakness, elevated creatine phosphokinase, and rhabdomyolysis have been reported during postmarketing experience.
Metabolic
Although progressive subcutaneous fat wasting has been attributed to the use of protease inhibitors, nucleoside reverse transcriptase inhibitors may have an independent contribution. This syndrome has been observed in patients naive to protease inhibitors, however, not to the same degree as in patients on a combination regimen that includes a protease inhibitor.
Metabolic side effects have included increased serum lipase (greater than or equal to 2.5 times ULN; 10%) and amylase (greater than 2 times ULN: up to 4.2%; greater than 3 times ULN: less than 1%). Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral agents; however, a causal relationship has not been established. Progressive subcutaneous fat wasting has been reported. Hyperglycemia and redistribution/accumulation of body fat have been reported during postmarketing experience.
Dermatologic
Dermatologic side effects have included skin rashes (up to 9%). Paronychia and periungual pyogenic granulomata have been reported. Alopecia, rash, and pruritus have been reported during postmarketing experience.
Psychiatric
Psychiatric side effects have included depressive disorders (9%).
Hypersensitivity
Hypersensitivity side effects have infrequently included angioedema and anaphylactoid reaction. Anaphylaxis and urticaria have been reported during postmarketing experience.
Immunologic
Immunologic side effects have included immune reconstitution syndrome. Autoimmune disorders (e.g., Graves' disease, polymyositis, and Guillain-Barre syndrome) have been reported in the setting of immune reconstitution.
Renal
Renal side effects have included at least one case of Fanconi syndrome.
Ocular
Ocular side effects have included eye redness.
TopMore Epivir resources
- Epivir Prescribing Information (FDA)
- Epivir Consumer Overview
- Epivir Advanced Consumer (Micromedex) - Includes Dosage Information
- Epivir MedFacts Consumer Leaflet (Wolters Kluwer)
- Lamivudine Prescribing Information (FDA)
- Lamivudine Monograph (AHFS DI)
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