EPIVIR-HBV SIDE EFFECTS
- Generic Name: lamivudine tablets and oral solution
- Brand Name: Epivir-HBV
SIDE EFFECTS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Lactic acidosis and severe hepatomegaly with steatosis.
- Exacerbation of hepatitis B after discontinuation of treatment.
- Risk of emergence of resistant HIV-1 infection.
- Risk of emergence of resistant HBV infection.
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 practice.
Adverse Reactions In Clinical Trials Of Adults With Chronic Hepatitis B Virus Infection
Clinical adverse reactions (regardless of investigator’s causality assessment) reported in greater or equal to 10% of subjects who received EPIVIR-HBV and reported at a rate greater than placebo are listed in Table 1.
Table 1. Clinical Adverse Reactionsa Reported in Greater than or Equal to 10% of Subjects who Received EPIVIR-HBV for 52 to 68 Weeks and at an Incidence Greater than Placebo (Trials 1-3)
| Adverse Event | EPIVIR-HBV (n = 332) |
Placebo (n = 200) |
| Ear, Nose, and Throat | ||
| Ear, nose, and throat infections | 25% | 21% |
| Sore throat | 13% | 8% |
| Gastrointestinal | ||
| Diarrhea | 14% | 12% |
| a Includes adverse events regardless of severity and causality assessment. | ||
Specified laboratory abnormalities reported in subjects who received EPIVIR-HBV and reported at a rate greater than in subjects who received placebo are listed in Table 3.
Table 2. Frequencies of Specified Laboratory Abnormalities Reported during Treatment at a Greater Frequency in Subjects Treated with EPIVIR-HBV than with Placebo (Trials 1-3)a
| Test (Abnormal Level) |
Subjects with Abnormality/Subjects with Observations | |
| EPIVIR-HBV | Placebo | |
| Serum Lipase ≥2.5 x ULNb | 10% | 7% |
| CPK ≥7 x baseline | 9% | 5% |
| Platelets <50,000/mm3 | 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. |
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In subjects followed for up to 16 weeks after discontinuation of treatment, posttreatment ALT elevations were observed more frequently in subjects who had received EPIVIR-HBV than in subjects who had received placebo. A comparison of ALT elevations between Weeks 52 and 68 in subjects who discontinued EPIVIR-HBV at Week 52 and subjects in the same trials who received placebo throughout the treatment course is shown in Table 4.
Table 3. Posttreatment ALT Elevations with No-Active-Treatment Follow-up (Trials 1 and 3)
| Abnormal Value | Subjects with ALT Elevation/ Subjects with Observationsa | |
| EPIVIR-HBVb | Placebob | |
| ALT ≥2 x baseline value | 27% | 19% |
| ALT ≥3 x baseline valuec | 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. |
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Adverse Reactions In Clinical Trials Of Pediatric Subjects With Chronic Hepatitis B Virus 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 EPIVIR-HBV.
Postmarketing Experience
In addition to adverse reactions reported from clinical trials, the following adverse reactions have been reported during postmarketing use of EPIVIR-HBV. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate the 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 Lymphatic System Disorders
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, posttreatment exacerbation of hepatitis [see BOX WARNING], pancreatitis.
Hypersensitivity
Anaphylaxis, urticaria.
Musculoskeletal
Cramps, rhabdomyolysis.
Nervous
Paresthesia, peripheral neuropathy.
Respiratory
Abnormal breath sounds/wheezing.
Skin
Alopecia, pruritus, rash.
SRC: NLM .