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 (exenatide injection) in five placebo-controlled clinical trials.

Table 1: Incidence (%) and Rate of Hypoglycemia When BYETTA (exenatide injection) was Used as Monotherapy or With Concomitant Antidiabetic Therapy in Five Placebo-Controlled Clinical Trials*

Immunogenicity

In the 30-week controlled trials of BYETTA (exenatide injection) add-on to metformin and/or sulfonylurea, 38% of patients had low titer antibodies to exenatide at 30 weeks. For this group, the level of glycemic control (hemoglobin A1c [HbA1c]) was generally comparable to that observed in those without antibody titers. An additional 6% of patients had higher titer antibodies at 30 weeks. In about half of this 6% (3% of the total patients given BYETTA (exenatide injection) in the 30-week controlled studies), the glycemic response to BYETTA (exenatide injection) was attenuated; the remainder had a glycemic response comparable to that of patients without antibodies.

In the 16-week trial of BYETTA (exenatide injection) add-on to thiazolidinediones, with or without metformin, 9% of patients had higher titer antibodies at 16 weeks. In the 24-week trial of BYETTA (exenatide injection) used as monotherapy, 3% of patients had higher titer antibodies at 24 weeks. Compared with patients who did not develop antibodies to BYETTA (exenatide injection) , on average the glycemic response in patients with higher titer antibodies was attenuated [see WARNINGS AND PRECAUTIONS].

Other Adverse Reactions

Monotherapy

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

Table 2: Treatment-Emergent Adverse Reactions ≥ 2% Incidence With BYETTA (exenatide injection) Used as Monotherapy (Excluding Hypoglycemia)*

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

Two of the 155 patients treated with BYETTA (exenatide injection) 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 (exenatide injection) add-on to metformin and/or sulfonylurea, adverse reactions (excluding hypoglycemia) with an incidence ≥ 2% and occurring more frequently in BYETTA (exenatide injection) -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 (exenatide injection) Treatment Used With Metformin and/or a Sulfonylurea (Excluding Hypoglycemia)*

Adverse reactions reported in ≥ 1.0 to < 2.0% of patients receiving BYETTA (exenatide injection) 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 (exenatide injection) -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 (exenatide injection) 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 (exenatide injection) -treated patients compared with placebo-treated patients.

Table 4: Treatment-Emergent Adverse Reactions ≥ 2% Incidence With BYETTA (exenatide injection) Used With a Thiazolidinedione, With or Without Metformin (Excluding Hypoglycemia)*

Adverse reactions reported in ≥ 1.0 to < 2.0% of patients receiving BYETTA (exenatide injection) and reported more frequently than with placebo included decreased appetite. Chills (n = 4) and injection-site reactions (n = 2) occurred only in BYETTA (exenatide injection) -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 (exenatide injection) arm. No serious adverse events were reported in the placebo arm.

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

Post-Marketing Experience

The following additional adverse reactions have been reported during post-approval use of BYETTA (exenatide injection) . 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

Read the Byetta (exenatide injection) Side Effects Center for a complete guide to possible side effects »

Orally Administered Drugs

The effect of BYETTA (exenatide injection) to slow gastric emptying can reduce the extent and rate of absorption of orally administered drugs. BYETTA (exenatide injection) should be used with caution in patients receiving oral medications that have narrow therapeutic index or require rapid gastrointestinal absorption [see ADVERSE REACTIONS]. For oral medications that are dependent on threshold concentrations for efficacy, such as contraceptives and antibiotics, patients should be advised to take those drugs at least 1 hour before BYETTA (exenatide injection) injection. If such drugs are to be administered with food, patients should be advised to take them with a meal or snack when BYETTA is not administered [see CLINICAL PHARMACOLOGY].

Warfarin

There are postmarketing reports of increased INR sometimes associated with bleeding, with concomitant use of warfarin and BYETTA [see ADVERSE REACTIONS]. In a drug interaction study, BYETTA (exenatide injection) did not have a significant effect on INR [see CLINICAL PHARMACOLOGY]. In patients taking warfarin, prothrombin time should be monitored more frequently after initiation or alteration of BYETTA (exenatide injection) therapy. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on warfarin.

Last reviewed on RxList: 6/20/2012
This monograph has been modified to include the generic and brand name in many instances.