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Byetta (Exenatide Injection) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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.

Hypoglycemia

Table 1 summarizes the incidence and rate of hypoglycemia with BYETTA in six placebo-controlled clinical trials.

Table 1: Incidence (%) and Rate of Hypoglycemia When BYETTA was Used as Monotherapy or With Concomitant Antidiabetic Therapy in Six Placebo-Controlled Clinical TrialsA hypoglycemic episode was recorded if a patient reported symptoms of hypoglycemia with or without a blood glucose value consistent with hypoglycemia. Severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring the assistance of another person and associated with either a blood glucose value consistent with hypoglycemia or prompt recovery after treatment for hypoglycemia.
BYETTA
Placebo twice daily 5 mcg twice daily 10 mcg twice daily
N = The number of Intent-to-Treat subjects in each treatment group.
Monotherapy (24 Weeks)
N 77 77 78
% Overall 1.3% 5.2% 3.8%
Rate (episodes/patient-year) 0.03 0.21 0.52
% Severe 0.0% 0.0% 0.0%
With Metformin (30 Weeks)
N 113 110 113
% Overall 5.3% 4.5% 5.3%
Rate (episodes/patient-year) 0.12 0.13 0.12
% Severe 0.0% 0.0% 0.0%
With a Sulfonylurea (30 Weeks)
N 123 125 129
% Overall 3.3% 14.4% 35.7%
Rate (episodes/patient-year) 0.07 0.64 1.61
% Severe 0.0% 0.0% 0.0%
With Metformin and a Sulfonylurea (30 Weeks)
N 247 245 241
% Overall 12.6% 19.2% 27.8%
Rate (episodes/patient-year) 0.58 0.78 1.71
% Severe 0.0% 0.4% 0.0%
With a Thiazolidinedione (16 Weeks)
N 112 not evaluated 121
% Overall 7.1% not evaluated 10.7%
Rate (episodes/patient-years) 0.56 not evaluated 0.98
% Severe 0.0% not evaluated 0.0%
With Insulin Glargine (30 Weeks) When BYETTA was initiated in combination with insulin glargine, the dose of insulin glargine was decreased by 20% in patients with an HbA1c ≤ 8.0 % to minimize the risk of hypoglycemia. See Table 9 for insulin dose titration algorithm.
N 122 not evaluated 137
% Overall 29.5% not evaluated 24.8%
Rate (episodes/patient-years) 1.58 not evaluated 1.61
% Severe 0.8% not evaluated 0.0%

Immunogenicity

Antibodies were assessed in 90% of subjects in the 30-week, 24-week and 16-week studies of BYETTA. In the 30-week controlled trials of BYETTA add-on to metformin and/or sulfonylurea, antibodies were assessed at 2- to 6-week intervals. The mean antibody titer peaked at week 6 and was reduced by 55% by week 30. Three hundred and sixty patients (38%) had low titer antibodies (<625) to exenatide at 30 weeks. The level of glycemic control (HbA1c) in these patients was generally comparable to that observed in the 534 patients (56%) without antibody titers. An additional 59 patients (6%) had higher titer antibodies (≥625) at 30 weeks. Of these patients, 32 (3% overall) had an attenuated glycemic response to BYETTA; the remaining 27 (3% overall) had a glycemic response comparable to that of patients without antibodies [see Warnings and Precautions ].

In the 16-week trial of BYETTA add-on to thiazolidinediones, with or without metformin, 36 patients (31%) had low titer antibodies to exenatide at 16 weeks. The level of glycemic control in these patients was generally comparable to that observed in the 69 patients (60%) without antibody titer. An additional 10 patients (9%) had higher titer antibodies at 16 weeks. Of these patients, 4 (4% overall) had an attenuated glycemic response to BYETTA; the remaining 6 (5% overall) had a glycemic response comparable to that of patients without antibodies [see Warnings and Precautions ].

In the 24-week trial of BYETTA used as monotherapy, 40 patients (28%) had low titer antibodies to exenatide at 24 weeks. The level of glycemic control in these patients was generally comparable to that observed in the 101 patients (70%) without antibody titers. An additional 3 patients (2%) had higher titer antibodies at 24 weeks. Of these patients, 1 (1% overall) had an attenuated glycemic response to BYETTA; the remaining 2 (1% overall) had a glycemic response comparable to that of patients without antibodies [see Warnings and Precautions].

Antibodies to exenatide were not assessed in the 30-week trial of BYETTA used in combination with insulin glargine.

Two hundred and ten patients with antibodies to exenatide in the BYETTA clinical trials were tested for the presence of cross-reactive antibodies to GLP-1 and/or glucagon. No treatment-emergent cross reactive antibodies were observed across the range of titers.

Other Adverse Reactions

Monotherapy

For the 24-week placebo-controlled study of BYETTA used as a monotherapy, Table 2 summarizes adverse reactions (excluding hypoglycemia) occurring with an incidence ≥2% and occurring more frequently in BYETTA-treated patients compared with placebo-treated patients.

Table 2: Treatment-Emergent Adverse Reactions ≥2% Incidence With BYETTA Used as Monotherapy (Excluding Hypoglycemia)In a 24-week placebo-controlled trial.
Monotherapy Placebo BID
N = 77
%
All BYETTA BID
N = 155
%
BID = twice daily.
Nausea 0 8
Vomiting 0 4
Dyspepsia 0 3

Adverse reactions reported in ≥1.0 to <2.0% of patients receiving BYETTA and reported more frequently than with placebo included decreased appetite, diarrhea, and dizziness. The most frequently reported adverse reaction associated with BYETTA, nausea, occurred in a dose-dependent fashion.

Two of the 155 patients treated with BYETTA withdrew due to adverse reactions of headache and nausea. No placebo-treated patients withdrew due to adverse reactions.

Combination Therapy

Add-on to metformin and/or sulfonylurea

In the three 30-week controlled trials of BYETTA add-on to metformin and/or sulfonylurea, adverse reactions (excluding hypoglycemia) with an incidence ≥2% and occurring more frequently in BYETTA-treated patients compared with placebo-treated patients [see Warnings and Precautions] are summarized in Table 3.

Table 3: Treatment-Emergent Adverse Reactions ≥2% Incidence and Greater Incidence With BYETTA Treatment Used With Metformin and/or a Sulfonylurea (Excluding Hypoglycemia)In three 30-week placebo-controlled clinical trials.
Placebo BID
N = 483
%
All BYETTA BID
N = 963
%
BID = twice daily.
Nausea 18 44
Vomiting 4 13
Diarrhea 6 13
Feeling Jittery 4 9
Dizziness 6 9
Headache 6 9
Dyspepsia 3 6
Asthenia 2 4
Gastroesophageal Reflux Disease 1 3
Hyperhidrosis 1 3

Adverse reactions reported in ≥1.0 to <2.0% of patients receiving BYETTA and reported more frequently than with placebo included decreased appetite. Nausea was the most frequently reported adverse reaction and occurred in a dose-dependent fashion. With continued therapy, the frequency and severity decreased over time in most of the patients who initially experienced nausea. Patients in the long-term uncontrolled open-label extension studies at 52 weeks reported no new types of adverse reactions than those observed in the 30-week controlled trials.

The most common adverse reactions leading to withdrawal for BYETTA-treated patients were nausea (3% of patients) and vomiting (1%). For placebo-treated patients, <1% withdrew due to nausea and none due to vomiting.

Add-on to thiazolidinedione with or without metformin

For the 16-week placebo-controlled study of BYETTA add-on to a thiazolidinedione, with or without metformin, Table 4 summarizes the adverse reactions (excluding hypoglycemia) with an incidence of ≥2% and occurring more frequently in BYETTA-treated patients compared with placebo-treated patients.

Table 4: Treatment-Emergent Adverse Reactions ≥2% Incidence With BYETTA Used With a Thiazolidinedione, With or Without Metformin (Excluding Hypoglycemia)In a 16-week placebo-controlled clinical trial.
With a TZD or TZD/MET Placebo
N = 112
%
All BYETTA BID
N = 121
%
BID = twice daily.
Nausea 15 40
Vomiting 1 13
Dyspepsia 1 7
Diarrhea 3 6
Gastroesophageal Reflux Disease 0 3

Adverse reactions reported in ≥1.0 to <2.0% of patients receiving BYETTA and reported more frequently than with placebo included decreased appetite. Chills (n = 4) and injection-site reactions (n = 2) occurred only in BYETTA-treated patients. The two patients who reported an injection-site reaction had high titers of antibodies to exenatide. Two serious adverse events (chest pain and chronic hypersensitivity pneumonitis) were reported in the BYETTA arm. No serious adverse events were reported in the placebo arm.

The most common adverse reactions leading to withdrawal for BYETTA-treated patients were nausea (9%) and vomiting (5%). For placebo-treated patients, <1% withdrew due to nausea.

Add-on to insulin glargine with or without metformin and/or thiazolidinedione

For the 30-week placebo-controlled study of BYETTA as add-on to insulin glargine with or without oral antihyperglycemic medications, Table 5 summarizes adverse reactions (excluding hypoglycemia) occurring with an incidence ≥2% and occurring more frequently in BYETTA-treated patients compared with placebo-treated patients.

Table 5: Treatment-Emergent Adverse Reactions ≥2% Incidence With BYETTA Used With Insulin Glargine With or Without Oral Antihyperglycemic Medications (Excluding Hypoglycemia)In a 30-week placebo-controlled clinical trial.
With Insulin Glargine Placebo
N = 122
%
All BYETTA BID
N = 137
%
BID = twice daily.
Nausea 8 41
Vomiting 4 18
Diarrhea 8 18
Headache 4 14
Constipation 2 10
Dyspepsia 2 7
Asthenia 1 5
Abdominal Distension 1 4
Decreased Appetite 0 3
Flatulence 1 2
Gastroesophageal Reflux Disease 1 2

The most frequently reported adverse reactions leading to withdrawal for BYETTA-treated patients were nausea (5.1%) and vomiting (2.9%). No placebo-treated patients withdrew due to nausea or vomiting.

Post-Marketing Experience

The following additional adverse reactions have been reported during post-approval use of BYETTA. Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Allergy/Hypersensitivity: injection-site reactions, generalized pruritus and/or urticaria, macular or papular rash, angioedema, anaphylactic reaction [see Warnings and Precautions].

Drug Interactions: International normalized ratio (INR) increased with concomitant warfarin use sometimes associated with bleeding [see Drug Interactions].

Gastrointestinal: nausea, vomiting, and/or diarrhea resulting in dehydration; abdominal distension, abdominal pain, eructation, constipation, flatulence, acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death [see Limitations of Use and Warnings and Precautions].

Neurologic: dysgeusia; somnolence

Renal and Urinary Disorders: altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure or acute renal failure (sometimes requiring hemodialysis), kidney transplant and kidney transplant dysfunction [see Warnings and Precautions].

Skin and Subcutaneous Tissue Disorders: alopecia



REPORTS OF SUSPECTED BYETTA SIDE EFFECTS / ADVERSE REACTIONS

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

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

Reported by a consumer/non-health professional from Germany on 2011-10-03

Patient: 56 year old male weighing 112.0 kg (246.4 pounds)

Reactions: Weight Decreased, Pancreatitis, Hypertriglyceridaemia

Suspect drug(s):
Byetta
    Dosage: 10 ug, bid
    Start date: 2010-11-12
    End date: 2011-07-28

Byetta
    Dosage: 5 ug, bid
    Indication: Type 2 Diabetes Mellitus
    Start date: 2010-10-15
    End date: 2010-11-11

Other drugs received by patient: Aspirin; Metformin HCL; Simvastatin; Metoprolol Succinate; Pantoprazole; Marcumar; Diovan; Metoprolol Succinate; Pravastatin; Diovan; Diclo-Divido



Possible Byetta side effects / adverse reactions in 63 year old male

Reported by a consumer/non-health professional from France on 2011-10-03

Patient: 63 year old male

Reactions: Syncope

Suspect drug(s):
Byetta



Possible Byetta side effects / adverse reactions in 55 year old female

Reported by a physician from United States on 2011-10-03

Patient: 55 year old female

Reactions: Weight Decreased, Fluid Intake Reduced, Renal Failure Acute, Decreased Appetite

Suspect drug(s):
Byetta



See index of all Byetta side effect reports >>

Drug label data at the top of this Page last updated: 2012-03-12

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