Baraclude

Baraclude Side Effects Center

Medical Editor: Charles Patrick Davis, MD, PhD

Baraclude (entecavir) is available in generic form. Baraclude is an antiviral nucleoside drug indicated for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals.

Baraclude tablets are available for oral administration in strengths of 0.5 mg and 1 mg. Baraclude should be administered on an empty stomach (at least 2 hours after a meal and 2 hours before the next meal). There are no adequate and well-controlled studies of Baraclude in pregnant women. Baraclude should be used during pregnancy or breastfeeding only if clearly needed and after careful consideration of the risks and benefits.

Our Baraclude (entecavir) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Baraclude in Detail - Patient Information: Side Effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

This medication may cause lactic acidosis (a build-up of lactic acid in the body, which can be fatal). Lactic acidosis can start slowly and get worse over time. Get emergency medical help if you have even mild symptoms of lactic acidosis, such as:

  • muscle pain or weakness;
  • numb or cold feeling in your arms and legs;
  • trouble breathing;
  • feeling dizzy, light-headed, tired, or very weak;
  • stomach pain, nausea with vomiting; or
  • slow or uneven heart rate.

Entecavir may also cause severe liver symptoms. Call your doctor at once if you have any of these liver symptoms:

  • low fever;
  • nausea, stomach pain, loss of appetite;
  • dark urine, clay-colored stools; or
  • jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

  • mild nausea, vomiting, diarrhea, upset stomach;
  • temporary hair loss;
  • headache;
  • skin rash; or
  • sleep problems (insomnia).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Baraclude (Entecavir) »

What is Patient Information Overview?

A concise overview of the drug for the patient or caregiver from First DataBank.

Baraclude Overview - Patient Information: Side Effects

SIDE EFFECTS: See also Warning section.

Headache, fatigue, dizziness, and nausea may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the entire patient information overview for Baraclude (Entecavir)»

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Baraclude FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

The following adverse reactions are discussed in other sections of the labeling:

Clinical Trial 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.

Compensated Liver Disease

Assessment of adverse reactions is based on four studies (AI463014, AI463022, AI463026, and AI463027) in which 1720 subjects with chronic hepatitis B virus infection and compensated liver disease received double-blind treatment with BARACLUDE 0.5 mg/day (n=679),

BARACLUDE 1 mg/day (n=183), or lamivudine (n=858) for up to 2 years. Median duration of therapy was 69 weeks for BARACLUDE-treated subjects and 63 weeks for lamivudine-treated subjects in Studies AI463022 and AI463027 and 73 weeks for BARACLUDE-treated subjects and 51 weeks for lamivudine-treated subjects in Studies AI463026 and AI463014. The safety profiles of BARACLUDE and lamivudine were comparable in these studies.

The most common adverse reactions of any severity ( ≥ 3%) with at least a possible relation to study drug for BARACLUDE-treated subjects were headache, fatigue, dizziness, and nausea. The most common adverse reactions among lamivudine-treated subjects were headache, fatigue, and dizziness. One percent of BARACLUDE-treated subjects in these four studies compared with 4% of lamivudine-treated subjects discontinued for adverse events or abnormal laboratory test results.

Clinical adverse reactions of moderate-severe intensity and considered at least possibly related to treatment occurring during therapy in four clinical studies in which BARACLUDE was compared with lamivudine are presented in Table 2.

Table 2: Clinical Adverse Reactionsa of Moderate-Severe Intensity (Grades 2-4) Reported in Four Entecavir Clinical Trials Through 2 Years

Body System/ Adverse Reaction Nucleoside-Naiveb Lamivudine-Refractoryc
BARACLUDE 0.5 mg
n=679
Lamivudine 100 mg
n=668
BARACLUDE 1 mg
n=183
Lamivudine 100 mg
n=190
Any Grade 2-4 adverse reactiona 15% 18% 22% 23%
Gastrointestinal
  Diarrhea < 1% 0 1% 0
  Dyspepsia < 1% < 1% 1% 0
  Nausea < 1% < 1% < 1% 2%
  Vomiting < 1% < 1% < 1% 0
General
  Fatigue 1% 1% 3% 3%
Nervous System
  Headache 2% 2% 4% 1%
  Dizziness < 1% < 1% 0 1%
  Somnolence < 1% < 1% 0 0
  Psychiatric Insomnia < 1% < 1% 0 < 1%
a Includes events of possible, probable, certain, or unknown relationship to treatment regimen.
b Studies AI463022 and AI463027.
c Includes Study AI463026 and the BARACLUDE 1 mg and lamivudine treatment arms of Study AI463014, a Phase 2 multinational, randomized, double-blind study of three doses of BARACLUDE (0.1, 0.5, and 1 mg) once daily versus continued lamivudine 100 mg once daily for up to 52 weeks in subjects who experienced recurrent viremia on lamivudine therapy.

Laboratory Abnormalities

Frequencies of selected treatment-emergent laboratory abnormalities reported during therapy in four clinical trials of BARACLUDE compared with lamivudine are listed in Table 3.

Table 3: Selected Treatment-Emergenta Laboratory Abnormalities Reported in Four Entecavir Clinical Trials Through 2 Years

Test Nucleoside--Naiveb Lamivudine-Refractoryc
BARACLUDE 0.5 mg
n=679
Lamivudine 100 mg
n=668
BARACLUDE 1 mg
n=183
Lamivudine 100 mg
n=190
Any Grade 3-4 laboratory abnormalityd 35% 36% 37% 45%
ALT > 10 x ULN and > 2 x baseline 2% 4% 2% 11%
ALT > 5.0 x ULN 11% 16% 12% 24%
Albumin < 2.5 g/dL < 1% < 1% 0 2%
Total bilirubin > 2.5 x ULN 2% 2% 3% 2%
Lipase ≥ 2.1 x ULN 7% 6% 7% 7%
Creatinine > 3.0 x ULN 0 0 0 0
Confirmed creatinine increase ≥ 0.5 mg/dL 1% 1% 2% 1%
Hyperglycemia, fasting > 250 mg/dL 2% 1% 3% 1%
Glycosuriae 4% 3% 4% 6%
Hematuriaf 9% 10% 9% 6%
3 Platelets < 50,000/mm < 1% < 1% < 1% < 1%
a On-treatment value worsened from baseline to Grade 3 or Grade 4 for all parameters except albumin (any on-treatment value < 2.5 g/dL), confirmed creatinine increase ≥ 0.5 mg/dL, and ALT > 10 x ULN and > 2 x baseline.
b Studies AI463022 and AI463027.
c Includes Study AI463026 and the BARACLUDE 1 mg and lamivudine treatment arms of Study AI463014, a Phase 2 multinational, randomized, double-blind study of three doses of BARACLUDE (0.1, 0.5, and 1 mg) once daily versus continued lamivudine 100 mg once daily for up to 52 weeks in subjects who experienced recurrent viremia on lamivudine therapy.
d Includes hematology, routine chemistries, renal and liver function tests, pancreatic enzymes, and urinalysis.
e Grade 3 = 3+, large, ≥ 500 mg/dL; Grade 4 = 4+, marked, severe.
f Grade 3 = 3+, large; Grade 4 = ≥ 4+, marked, severe, many.
ULN=upper limit of normal.

Among BARACLUDE-treated subjects in these studies, on-treatment ALT elevations greater than 10 times the upper limit of normal (ULN) and greater than 2 times baseline generally resolved with continued treatment. A majority of these exacerbations were associated with a ≥ 2 log10/mL reduction in viral load that preceded or coincided with the ALT elevation. Periodic monitoring of hepatic function is recommended during treatment.

Exacerbations of Hepatitis after Discontinuation of Treatment

An exacerbation of hepatitis or ALT flare was defined as ALT greater than 10 times ULN and greater than 2 times the subject's reference level (minimum of the baseline or last measurement at end of dosing). For all subjects who discontinued treatment (regardless of reason), Table 4 presents the proportion of subjects in each study who experienced post-treatment ALT flares. In these studies, a subset of subjects was allowed to discontinue treatment at or after 52 weeks if they achieved a protocol-defined response to therapy. If BARACLUDE is discontinued without regard to treatment response, the rate of post-treatment flares could be higher. [See also WARNINGS AND PRECAUTIONS]

Table 4: Exacerbations of Hepatitis During Off-Treatment Follow-up, Subjects in Studies AI463022, AI463027, and AI463026

  Subjects with ALT Elevations > 10 x ULN and > 2 x Referencea
BARACLUDE Lamivudine
Nucleoside-naive
  HBeAg-positive 4/174 (2%) 13/147 (9%)
  HBeAg-negative 24/302 (8%) 30/270 (11%)
Lamivudine-refractory 6/52 (12%) 0/16
a Reference is the minimum of the baseline or last measurement at end of dosing. Median time to off-treatment exacerbation was 23 weeks for BARACLUDE-treated subjects and 10 weeks for lamivudine-treated subjects.

Decompensated Liver Disease

Study AI463048 was a randomized, open-label study of BARACLUDE 1 mg once daily versus adefovir dipivoxil 10 mg once daily given for up to 48 weeks in adult subjects with chronic HBV infection and evidence of hepatic decompensation, defined as a Child-Turcotte-Pugh (CTP) score of 7 or higher [see Clinical Studies]. Among the 102 subjects receiving BARACLUDE, the most common treatment-emergent adverse events of any severity, regardless of causality, occurring through Week 48 were peripheral edema (16%), ascites (15%), pyrexia (14%), hepatic encephalopathy (10%), and upper respiratory infection (10%). Clinical adverse reactions not listed in Table 2 that were observed through Week 48 include blood bicarbonate decreased (2%) and renal failure ( < 1%).

Eighteen of 102 (18%) subjects treated with BARACLUDE and 18/89 (20%) subjects treated with adefovir dipivoxil died during the first 48 weeks of therapy. The majority of deaths (11 in the BARACLUDE group and 16 in the adefovir dipivoxil group) were due to liver-related causes such as hepatic failure, hepatic encephalopathy, hepatorenal syndrome, and upper gastrointestinal hemorrhage. The rate of hepatocellular carcinoma (HCC) through Week 48 was 6% (6/102) for subjects treated with BARACLUDE and 8% (7/89) for subjects treated with adefovir dipivoxil. Five percent of subjects in either treatment arm discontinued therapy due to an adverse event through Week 48.

No subject in either treatment arm experienced an on-treatment hepatic flare (ALT > 2 x baseline and > 10 x ULN) through Week 48. Eleven of 102 (11%) subjects treated with BARACLUDE and 11/89 (13%) subjects treated with adefovir dipivoxil had a confirmed increase in serum creatinine of 0.5 mg/dL through Week 48.

HIV/HBV Co-Infected

The safety profile of BARACLUDE 1 mg (n=51) in HIV/HBV co-infected subjects enrolled in Study AI463038 was similar to that of placebo (n=17) through 24 weeks of blinded treatment and similar to that seen in non-HIV infected subjects [see WARNINGS AND PRECAUTIONS].

Liver Transplant Recipients

Among 65 subjects receiving BARACLUDE in an open-label, post-liver transplant trial [see Use In Specific Populations], the frequency and nature of adverse events were consistent with those expected in patients who have received a liver transplant and the known safety profile of BARACLUDE.

Postmarketing Experience

The following adverse reactions have been reported during postmarketing use of BARACLUDE. Because these reactions were reported voluntarily from a population of unknown size, it is not possible to reliably estimate their frequency or establish a causal relationship to BARACLUDE exposure.

Immune system disorders: Anaphylactoid reaction.

Metabolism and nutrition disorders: Lactic acidosis.

Hepatobiliary disorders: Increased transaminases.

Skin and subcutaneous tissue disorders: Alopecia, rash.

Read the entire FDA prescribing information for Baraclude (Entecavir) »

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Baraclude - User Reviews

Baraclude User Reviews

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