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Hepsera (Adefovir Dipivoxil) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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

  • Severe acute exacerbations of Hepatitis [ see Boxed Warning, Warnings and Precautions]
  • Nephrotoxicity [ see Boxed Warning, Warnings and Precautions ]

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.

Clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of treatment with HEPSERA.

Adverse reactions to HEPSERA identified from placebo-controlled and open label studies include the following: asthenia, headache, abdominal pain, diarrhea, nausea, dyspepsia, flatulence, increased creatinine, and hypophosphatemia.

The incidence of these adverse reactions in studies 437 and 438, where 522 patients with chronic hepatitis B and compensated liver disease received double-blind treatment with HEPSERA (n=294) or placebo (n=228) for 48 weeks is presented in Table 2. Patients who received open-label HEPSERA for up to 240 weeks in Study 438 reported adverse reactions similar in nature and severity to those reported in the first 48 weeks.

Table 2 Adverse Reactions (Grades 1–4) Reported in ≥3% of All HEPSERA-Treated Patients in Pooled Studies 437–438 Studies (0–48 Weeks)In these studies, the overall incidence of adverse reactions with HEPSERA was similar to that reported with placebo. The incidence of adverse reactions is derived from treatment-related events as identified by the study investigators.
Adverse ReactionHEPSERA
10mg
(N=294)
Placebo
(N=228)
Asthenia13%14%
Headache9%10%
Abdominal Pain9%11%
Nausea5%8%
Flatulence4%4%
Diarrhea3%4%
Dyspepsia3%2%

No patients treated with HEPSERA developed a confirmed serum creatinine increase ≥0.5 mg/dL or confirmed phosphorus decrease ≤2 mg/dL from baseline by week 48. By week 96, 2% of HEPSERA-treated patients, by Kaplan-Meier estimate, had increases in serum creatinine ≥0.5 mg/dL from baseline (no placebo-controlled results were available for comparison beyond week 48). For patients who chose to continue HEPSERA for up to 240 weeks in Study 438, 4 of 125 patients (3%) had a confirmed increase of 0.5 mg/dL from baseline. The creatinine elevation resolved in 1 patient who permanently discontinued treatment and remained stable in 3 patients who continued treatment. For 65 patients who chose to continue HEPSERA for up to 240 weeks in Study 437, 6 had a confirmed increase in serum creatinine of ≥0.5 mg/dL from baseline with 2 patients discontinuing from the study due to the elevated serum creatinine concentration. See Adverse Reactions for changes in serum creatinine in patients with underlying renal insufficiency at baseline.

Special Risk Patients

Pre- and Post-Liver Transplantation Patients

Additional adverse reactions observed from an open-label study (study 435) in pre- and post- liver transplantation patients with chronic hepatitis B and lamivudine-resistant hepatitis B administered HEPSERA once daily for up to 203 weeks include: abnormal renal function, renal failure, vomiting, rash, and pruritus.

Changes in renal function occurred in pre-and post-liver transplantation patients with risk factors for renal dysfunction, including concomitant use of cyclosporine and tacrolimus, renal insufficiency at baseline, hypertension, diabetes, and on-study transplantation. Therefore, the contributory role of HEPSERA to these changes in renal function is difficult to assess.

Increases in serum creatinine ≥0.3 mg/dL from baseline were observed in 37% and 53% of pre-liver transplantation patients by weeks 48 and 96, respectively, by Kaplan-Meier estimates. Increases in serum creatinine ≥0.3 mg/dL from baseline were observed in 32% and 51% of post-liver transplantation patients by weeks 48 and 96, respectively, by Kaplan-Meier estimates. Serum phosphorus values <2 mg/dL were observed in 3/226 (1.3%) of pre-liver transplantation patients and in 6/241 (2.5%) of post-liver transplantation patients by last study visit. Four percent (19 of 467) of patients discontinued treatment with HEPSERA due to renal adverse events.

Pediatric Patients

Assessment of adverse reactions is based on a placebo-controlled study (study 518) in which 173 pediatric patients aged 2 to <18 years with chronic hepatitis B and compensated liver disease received double-blind treatment with HEPSERA (n=115), or placebo (n=58) for 48 weeks [see Clinical Studies and Use In Specific Populations].

The safety profile of HEPSERA in patients ≥12 to <18 years of age (n=56) was similar to that observed in adults. No pediatric patients treated with HEPSERA developed a confirmed serum creatinine increase ≥ 0.5 mg/dL or confirmed phosphorus decrease to <2 mg/dL from baseline by Week 48.

Post-Marketing Experience

In addition to adverse reaction reports from clinical trials, the following possible adverse reactions have also been identified during post-approval use of adefovir dipivoxil. Because these events have been reported voluntarily from a population of unknown size, estimates of frequency cannot be made.

Metabolism and Nutrition Disorders: hypophosphatemia

Musculoskeletal System and Connective Tissue Disorders: myopathy, osteomalacia (both associated with proximal renal tubulopathy)

Renal and Urinary Disorders: renal failure, proximal renal tubulopathy, Fanconi syndrome



REPORTS OF SUSPECTED HEPSERA SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Hepsera. The information is not vetted and should not be considered as verified clinical evidence.

Possible Hepsera side effects / adverse reactions in 56 year old male

Reported by a pharmacist from Japan on 2011-07-01

Patient: 56 year old male

Reactions: Multiple Fractures

Suspect drug(s):
Hepsera
    Dosage: 10mg per day
    Administration route: Oral
    Indication: Hepatitis B

Lamivudine (Epivir Hbv)
    Administration route: Oral

Other drugs received by patient: Rilutek; Famotidine; Lioresal



Possible Hepsera side effects / adverse reactions in male

Reported by a physician from Japan on 2011-09-06

Patient: male

Reactions: Fanconi Syndrome

Suspect drug(s):
Lamivudine (Epivir Hbv)
    Administration route: Oral

Hepsera
    Administration route: Oral
    Indication: Hepatitis B



Possible Hepsera side effects / adverse reactions in 79 year old male

Reported by a physician from Spain on 2011-11-15

Patient: 79 year old male

Reactions: Hypophosphataemia, Osteomalacia

Adverse event resulted in: hospitalization

Suspect drug(s):
Hepsera

Other drugs received by patient: Omeprazole; Zolpidem Tartrate; Aspirin; Clonazepam; Urotrol /01350202/; Pantoprazole



See index of all Hepsera side effect reports >>

Drug label data at the top of this Page last updated: 2008-05-27

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