Byetta exenatide 250 ug/mL Injection, 1 cartridge
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the GLP-1 Receptor Agonist class.
Where does this data come from?
🏭 Manufacturer & labeler
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🩺 Clinical
Exenatide injection is used with diet and exercise to lower blood sugar in certain people with type 2 diabetes (condition in which blood sugar is too high because the body does not make or use insulin normally). Exenatide is in a class of medications called incretin mimetics. It works by stimulating the pancreas to secrete insulin when blood sugar levels are high. Insulin helps move sugar from the blood into other body tissues where it is used for energy. Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, s...
Read the full MedlinePlus article ↗- No, exenatide is not insulin. Instead of replacing insulin, it works like a natural gut hormone called GLP-1 to encourage your own pancreas to release insulin — but only when your...
- What exactly does exenatide do — is it the same as insulin?
- Yes, nausea is the most common side effect and it can be pretty bothersome at first, especially when you start or when your dose increases. The good news is that for most people it...
- I feel nauseous when I take it — is that normal, and will it go away?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Exenatide — tap one for details:
Exenatide may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII Q40Q9N063P
Acetic acid is a weak organic acid commonly used in medicines as a buffer and pH adjuster. It helps maintain the proper acidity level to ensure the drug remains stable and effective in its formulation.
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UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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2.2 mg / 1 mL
UNII GGO4Y809LO
Metacresol is a preservative derived from coal tar or petroleum. It prevents bacterial and fungal growth in liquid medicines, helping keep the product safe and stable during storage.
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UNII 4550K0SC9B
Sodium acetate is a salt derived from acetic acid. It acts as a buffer to help maintain the medicine's pH stability and may serve as a preservative or solubilizer in liquid formulations.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
5 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $340.101 | $816.24 / 2.4 ml |
| Medicaid paysCMS SDUD · 12 mo | $342.53 | $822.07 / 2.4 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Exenatide 250 ug/mL 70121-1686-01 | Amneal | 1 cartridge | $300.168 | — | Availability likely | save 12% |
| Byetta 250 ug/mLthis 00310-6524-01 | AstraZeneca | 1 cartridge | $340.101 | — | FDA listed | — |
| Byetta 250 ug/mL 00310-6512-01 | AstraZeneca | 1 cartridge | $681.263 | — | FDA listed | +100% |
| Exenatide 250 ug/mL 70121-1685-01 | Amneal | 1 cartridge | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00310-6524-01 You're viewing this | 1 CARTRIDGE in 1 CARTON (0310-6524-01) / 2.4 mL in 1 CARTRIDGE | 2014-12-12 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE BYETTA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use • BYETTA contains exenatide. Coadministration with other exenatide-containing products is not recommended.
BYETTA (exenatide) is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1 , 14 ) Limitations of Use • Coadministration with other exenatide-containing products is not recommended ( 1 ).
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Inject subcutaneously within 60 minutes prior to morning and evening meals (or before the two main meals of the day, approximately 6 hours or more apart). ( 2.1 ) • Initiate at 5 mcg per dose twice daily; increase to 10 mcg twice daily after 1 month based on clinical response. ( 2.1 )
2.1Recommended Dosing • Initiate BYETTA at 5 mcg administered subcutaneously twice daily at any time within the 60-minute period before the morning and evening meals (or before the two main meals of the day, approximately 6 hours or more apart). Do not administer after a meal. • Based on clinical response, the dose of BYETTA can be increased to 10 mcg twice daily which is recommended after 1 month of therapy, in order to reduce the risk of gastrointestinal adverse reactions [see Warnings and Precautions (5.5) and Adverse Reactions (6.1) ] . • Administer as a subcutaneous injection in the thigh, abdomen, or upper arm. • Rotate injections sites with each dose.
Do not use the same site for each injection. • Inspect visually for particulate matter and discoloration. Only use BYETTA if the solution appears clear, colorless, and contains no particles. • When using BYETTA with insulin, administer as separate injections and never mix. It is acceptable to inject BYETTA and insulin in the same body region, but the injections should not be adjacent to each other. • If a dose is missed, resume the treatment regimen as prescribed with the next scheduled dose.
2.1Recommended Dosing • Initiate BYETTA at 5 mcg administered subcutaneously twice daily at any time within the 60-minute period before the morning and evening meals (or before the two main meals of the day, approximately 6 hours or more apart). Do not administer after a meal. • Based on clinical response, the dose of BYETTA can be increased to 10 mcg twice daily which is recommended after 1 month of therapy, in order to reduce the risk of gastrointestinal adverse reactions [see Warnings and Precautions (5.5) and Adverse Reactions (6.1) ] . • Administer as a subcutaneous injection in the thigh, abdomen, or upper arm. • Rotate injections sites with each dose.
Do not use the same site for each injection. • Inspect visually for particulate matter and discoloration. Only use BYETTA if the solution appears clear, colorless, and contains no particles. • When using BYETTA with insulin, administer as separate injections and never mix. It is acceptable to inject BYETTA and insulin in the same body region, but the injections should not be adjacent to each other. • If a dose is missed, resume the treatment regimen as prescribed with the next scheduled dose.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS BYETTA injection is a clear, colorless solution of exenatide supplied as follows: • 5 mcg per dose in a single-patient-use prefilled pen containing 300 mcg/1.2 mL (250 mcg/mL), 60 doses. • 10 mcg per dose in a single-patient-use prefilled pen containing 600 mcg/2.4 mL (250 mcg/mL), 60 doses. BYETTA injection is supplied as: • 5 mcg per dose, in a single patient use prefilled pen containing 300 mcg/1.2 mL (250 mcg/mL), 60 doses. • 10 mcg per dose, in a single patient use prefilled pen containing 600 mcg/2.4 mL (250 mcg/mL), 60 doses.
⛔ Contraindications ▾
4 CONTRAINDICATIONS BYETTA is contraindicated in patients with: • A prior severe hypersensitivity reaction to exenatide or to any of the excipients in BYETTA. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with BYETTA [see Warnings and Precautions (5.7) ]. • A history of drug-induced immune-mediated thrombocytopenia from exenatide products. Serious bleeding, which may be fatal, from drug-induced immune-mediated thrombocytopenia has been reported with exenatide use [see Warnings and Precautions (5.8) ] . • History of severe hypersensitivity to exenatide or any of the excipients in BYETTA.
(4) • History of drug-induced immune-mediated thrombocytopenia from exenatide products. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Acute Pancreatitis : Has been observed in patients treated with GLP-1 receptor agonists, including BYETTA. Discontinue if pancreatitis is suspected. ( 5.1 ) • Never share a BYETTA pen between patients, even if the needle is changed.
( 5.2 ) • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin: Patients taking an insulin secretagogue or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Reduction in the dose of insulin secretagogues or insulin may be necessary. ( 5.3 ) • Acute Kidney Injury Due to Volume Depletion : Monitor renal function in patients reporting adverse reactions that could lead to volume depletion ( 5.4 ) • Severe Gastrointestinal Adverse Reactions : Use has been associated with gastrointestinal adverse reactions, sometimes severe.
BYETTA is not recommended in patients with severe gastroparesis. ( 5.5 ) • Immunogenicity: Patients may develop antibodies to exenatide. If there is worsening glycemic control or failure to achieve target glycemic control, consider alternative antidiabetic therapy.
( 5.6 ) • Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis and angioedema) have been reported. Discontinue BYETTA and promptly seek medical advice. ( 5.7 ) • Drug-induced Immune-mediated Thrombocytopenia: Serious bleeding which may be fatal has been reported.
Discontinue BYETTA promptly and avoid re-exposure to exenatide. ( 5.8 ) • Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated. ( 5.9 ) • Pulmonary Aspiration During General Anesthesia or Deep Sedation: Has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures.
Instruct patients to inform healthcare providers of any planned surgeries or procedures. ( 5.10 )
5.1Acute Pancreatitis Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with glucagon-like peptide-1 (GLP-1) receptor agonists, including BYETTA [see Adverse Reactions (6.2) ] . After initiation of BYETTA, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue BYETTA and initiate appropriate management.
5.2Never Share a BYETTA Pen Between Patients BYETTA pens must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.
5.3Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin Patients receiving BYETTA in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia including severe hypoglycemia [see Adverse Reactions (6) and Drug Interactions (7) ] . The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
5.4Acute Kidney Injury Due to Volume Depletion There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with GLP-1 receptor agonists, BYETTA [see Adverse Reactions (6.2) ] . The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea [see Adverse Reactions (6) ] . Monitor renal function in patients reporting adverse reactions to BYETTA that could lead to volume depletion, especially during dosage initiation and escalation of BYETTA.
BYETTA is not recommended in patients with severe renal impairment (creatinine clearance <30 mL/min) or end-stage renal disease and should be used with caution in patients with re…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: • Acute Pancreatitis [see Warnings and Precautions (5.1) ] • Never Share a BYETTA Pen Between Patients [see Warnings and Precautions (5.2) ] • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin [see Warnings and Precautions (5.3) ] • Acute Kidney Injury Due to Volume Depletion [see Warnings and Precautions (5.4) ] • Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.5) ] • Immunogenicity [see Warnings and Precautions (5.6) ] • Hypersensitivity [see Warnings and Precautions (5.7) ] • Drug-Induced Thrombocytopenia [see Warnings and Precautions (5.8) ] • Acute Gallbladder Disease [see Warnings and Precautions (5.9) ] • Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions (5.10) ] • Most common (≥5%) and occurring more frequently than placebo in clinical trials: nausea, hypoglycemia, vomiting, diarrhea, feeling jittery, dizziness, headache, dyspepsia, constipation, asthenia.
Nausea usually decreases over time. ( 5.3 , 6 ) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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 Trials A 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 documented blood glucose value <54 mg/dL or prompt recovery after treatment for hypoglycemia. Placebo BID BYETTA 5 mcg BID BYETTA 10 mcg BID 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 with or without Metformin and/or Thiazolidinedione (30 Weeks) When BYETTA was initiated in combination with insulin glargine, the dose of insulin glargine was decreased by 20% in patients with an HbA 1c ≤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% N = number of Intent-to-Treat subjects in each treatment group. 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.
Th…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • May impact absorption of orally administered medications. ( 7 ) • Warfarin: Postmarketing reports of increased INR sometimes associated with bleeding. Monitor INR frequently until stable upon initiation or alteration of BYETTA therapy.
( 7 ) Generic Section Table 6: Clinically Relevant Interactions with BYETTA Concomitant Use of Insulin Secretagogues or Insulin Clinical Impact Exenatide promotes insulin release from pancreatic beta-cells in the presence of elevated glucose concentrations. The risk of hypoglycemia is increased when exenatide is used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin [see Warnings and Precautions (5.3) and Adverse Reactions (6) ] . Intervention When initiating BYETTA, consider reducing the dose of concomitantly administered insulin secretagogue or insulin to reduce the risk of hypoglycemia.
Warfarin Clinical Impact In a drug interaction study, BYETTA did not have a significant effect on INR [see Clinical Pharmacology (12.3) ] . There have been postmarketing reports for BYETTA of increased INR with concomitant use of warfarin, sometimes associated with bleeding [see Adverse Reactions (6.2) ] . Intervention In patients taking warfarin, the prothrombin time should be monitored more frequently after initiation or alteration of BYETTA therapy.
Once a stable prothrombin time has been documented, the prothrombin time can be monitored at the intervals recommended for patients taking warfarin. Orally Administered Drugs (e.g., acetaminophen) Clinical Impact Exenatide slows gastric emptying. Therefore, BYETTA has the potential to reduce the rate of absorption of orally administered drugs [see Clinical Pharmacology (12.3) ].
Intervention Use caution when administering oral medications with BYETTA where a slower rate of oral absorption may be clinically meaningful. 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 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 (12.3) ] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Pregnancy: Use during pregnancy only if the potential benefit justifies the risk to the fetus. (8.1)
8.1Pregnancy Risk Summary Limited data with BYETTA in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations ). Based on animal reproduction studies, there may be risks to the fetus from exposure to BYETTA during pregnancy.
BYETTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal reproduction studies identified increased adverse fetal and neonatal outcomes from exposure to exenatide during pregnancy and lactation in association with maternal effects. In mice, exenatide administered during gestation and lactation caused increased neonatal deaths at systemic exposure 3-times the human exposure resulting from the maximum recommended human dose (MRHD) of 20 mcg/day for BYETTA (see Data ) .
The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with an HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations Disease-associated maternal and/or embryofetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Data Animal Data In studies evaluating reproduction and development in pregnant mice and rabbits, maternal animals were administered exenatide, the active ingredient in BYETTA, by subcutaneous injection twice a day.
In pregnant mice given 6, 68, 460, or 760 mcg/kg/day exenatide during fetal organogenesis, skeletal variations associated with slowed fetal growth, including changes in number of rib pairs or vertebral ossifications sites, and wavy ribs were observed at 760 mcg/kg/day, a dose that produced maternal toxicity and yielded systemic exposure 390-times the human exposure resulting from the MRHD of BYETTA based on AUC comparison. In pregnant rabbits given 0.2, 2, 22, 156, or 260 mcg/kg/day exenatide during fetal organogenesis, irregular fetal skeletal ossifications were observed at 2 mcg/kg/day, a dose yielding systemic exposure up to 12-times the human exposure from the MRHD of BYETTA based on AUC comparison.
In maternal mice given 6, 68, or 760 mcg/kg/day exenatide from gestation day 6 through lactation day 20 (weaning), an increased number of neonatal deaths was observed on postpartum days 2 to 4 in dams given 6 mcg/kg/day, a dose yielding a systemic exposure 3-times the human exposure from the MRHD of BYETTA based on AUC comparison.
8.2Lactation Risk Summary There is no information regarding the presence of BYETTA, in human milk, the effects of BYETTA on the breastfed infant, or the effects of BYETTA on milk production. Exenatide was present in the milk of lactating mice. However, due to species-specific differences in lactation physiology, the clinical relevance of these data is not clear (see Data ) .
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BYETTA and any potential adverse effects on the breastfed child from BYETTA or from the underlying maternal condition. Data In lactating mice subcutaneously injected twice a day with exenatide, the concentration of exenatide in milk was up to 2.5% of the concentration in maternal plasma.
8.4 Pediatric Use The safety and effectiveness of BYETTA…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Limited data with BYETTA in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations ). Based on animal reproduction studies, there may be risks to the fetus from exposure to BYETTA during pregnancy.
BYETTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal reproduction studies identified increased adverse fetal and neonatal outcomes from exposure to exenatide during pregnancy and lactation in association with maternal effects. In mice, exenatide administered during gestation and lactation caused increased neonatal deaths at systemic exposure 3-times the human exposure resulting from the maximum recommended human dose (MRHD) of 20 mcg/day for BYETTA (see Data ) .
The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with an HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations Disease-associated maternal and/or embryofetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Data Animal Data In studies evaluating reproduction and development in pregnant mice and rabbits, maternal animals were administered exenatide, the active ingredient in BYETTA, by subcutaneous injection twice a day.
In pregnant mice given 6, 68, 460, or 760 mcg/kg/day exenatide during fetal organogenesis, skeletal variations associated with slowed fetal growth, including changes in number of rib pairs or vertebral ossifications sites, and wavy ribs were observed at 760 mcg/kg/day, a dose that produced maternal toxicity and yielded systemic exposure 390-times the human exposure resulting from the MRHD of BYETTA based on AUC comparison. In pregnant rabbits given 0.2, 2, 22, 156, or 260 mcg/kg/day exenatide during fetal organogenesis, irregular fetal skeletal ossifications were observed at 2 mcg/kg/day, a dose yielding systemic exposure up to 12-times the human exposure from the MRHD of BYETTA based on AUC comparison.
In maternal mice given 6, 68, or 760 mcg/kg/day exenatide from gestation day 6 through lactation day 20 (weaning), an increased number of neonatal deaths was observed on postpartum days 2 to 4 in dams given 6 mcg/kg/day, a dose yielding a systemic exposure 3-times the human exposure from the MRHD of BYETTA based on AUC comparison.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of BYETTA have not been established in pediatric patients. Effectiveness of BYETTA was not demonstrated in a randomized, double-blind, placebo-controlled study conducted in 120 pediatric patients (78 received BYETTA and 42 received placebo) aged 10 to 17 years with type 2 diabetes mellitus.
🧓 Geriatric Use ▾
8.5Geriatric Use Population pharmacokinetic analysis of patients ranging from 22 to 73 years of age suggests that age does not influence the pharmacokinetic properties of exenatide [see Clinical Pharmacology (12.3) ] . BYETTA was studied in 282 patients 65 years of age or older and in 16 patients 75 years of age or older. No differences in safety or effectiveness were observed between these patients and younger patients.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly based on renal function.
🆘 Overdosage ▾
10 OVERDOSAGE In a clinical study of BYETTA, three patients with type 2 diabetes each experienced a single overdose of 100 mcg SC (10 times the maximum recommended dose). Effects of the overdoses included severe nausea, severe vomiting, and rapidly declining blood glucose concentrations. One of the three patients experienced severe hypoglycemia requiring parenteral glucose administration.
The three patients recovered without complication. In the event of overdose, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Initiate appropriate supportive treatment according to the patient's clinical signs and symptoms.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Incretins, such as glucagon-like peptide-1 (GLP-1), enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. BYETTA is a GLP-1 receptor agonist that enhances glucose-dependent insulin secretion by the pancreatic beta-cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. The amino acid sequence of exenatide partially overlaps that of human GLP-1.
Exenatide has been shown to bind and activate the human GLP-1 receptor in vitro . This leads to an increase in both glucose-dependent synthesis of insulin, and in vivo secretion of insulin from pancreatic beta cells, by mechanisms involving cyclic AMP and/or other intracellular signaling pathways. BYETTA improves glycemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes through the actions described below.
12.2Pharmacodynamics Glucose-Dependent Insulin Secretion BYETTA has acute effects on pancreatic beta-cell responsiveness to glucose leading to insulin release predominantly in the presence of elevated glucose concentrations. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia. However, BYETTA does not impair the normal glucagon response to hypoglycemia.
First-Phase Insulin Response In healthy individuals, robust insulin secretion occurs during the first 10 minutes following intravenous (IV) glucose administration. This secretion, known as the "first-phase insulin response," is characteristically absent in patients with type 2 diabetes. The loss of the first-phase insulin response is an early beta-cell defect in type 2 diabetes.
Administration of BYETTA at therapeutic plasma concentrations restored first-phase insulin response to an IV bolus of glucose in patients with type 2 diabetes (Figure 1). Both first-phase insulin secretion and second-phase insulin secretion were significantly increased in patients with type 2 diabetes treated with BYETTA compared with saline (p<0.001 for both). Figure 1: Mean (+SEM) Insulin Secretion Rate during Infusion of BYETTA or Saline in Patients with Type 2 Diabetes and during Infusion of Saline in Healthy Subjects Figure 1 Glucagon Secretion In patients with type 2 diabetes, BYETTA moderates glucagon secretion and lowers serum glucagon concentrations during periods of hyperglycemia.
Lower glucagon concentrations lead to decreased hepatic glucose output and decreased insulin demand. Gastric Emptying BYETTA slows gastric emptying, thereby reducing the rate at which meal-derived glucose appears in the circulation. Food Intake In both animals and humans, administration of exenatide has been shown to reduce food intake.
Postprandial Glucose In patients with type 2 diabetes, BYETTA reduces postprandial plasma glucose concentrations (Figure 2). Figure 2: Mean (+SEM) Postprandial Plasma Glucose Concentrations on Day 1 of BYETTA a Treatment in Patients with Type 2 Diabetes Treated with Metformin, a Sulfonylurea, or Both (N=54) Figure 2 Fasting Glucose In a single-dose crossover study in patients with type 2 diabetes and fasting hyperglycemia, immediate insulin release followed injection of BYETTA. Plasma glucose concentrations were significantly reduced with BYETTA compared with placebo (Figure 3).
Figure 3: Mean (+SEM) Serum Insulin and Plasma Glucose Concentrations Following a One-Time Injection of BYETTA a or Placebo in Fasting Patients with Type 2 Diabetes (N=12) Figure 3 Cardiac Electrophysiology The effect of exenatide 10 µg subcutaneously on QTc interval was evaluated in a randomized, placebo-, and active-controlled (moxifloxacin 400 mg) crossover thorough QTc study in 62 healthy subjects. In this study with demonstrated ability to detect small effects, the upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc was below 10 msec.
Thus, BYETT…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Incretins, such as glucagon-like peptide-1 (GLP-1), enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. BYETTA is a GLP-1 receptor agonist that enhances glucose-dependent insulin secretion by the pancreatic beta-cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. The amino acid sequence of exenatide partially overlaps that of human GLP-1.
Exenatide has been shown to bind and activate the human GLP-1 receptor in vitro . This leads to an increase in both glucose-dependent synthesis of insulin, and in vivo secretion of insulin from pancreatic beta cells, by mechanisms involving cyclic AMP and/or other intracellular signaling pathways. BYETTA improves glycemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes through the actions described below.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied BYETTA (exenatide) Injection is a clear, colorless solution supplied as: • 5 mcg per dose, in a single-patient-use prefilled pen containing 300 mcg/1.2 mL (250 mcg/mL), 60 doses, NDC 0310-6512-01. • 10 mcg per dose, in a single-patient-use prefilled pen containing 600 mcg/2.4 mL (250 mcg/mL), 60 doses, NDC 0310-6524-01.
16.2Storage and Handling • Store BYETTA in the refrigerator at 36°F to 46°F (2°C to 8°C). • After first use, BYETTA can be kept at a temperature not to exceed 77°F (25°C). • Do not freeze. Do not use BYETTA if it has been frozen. • Protect BYETTA from light. • Discard the pen 30 days after first use, even if some drug remains in the pen. • Use a puncture-resistant container to discard the needles. Do not reuse or share needles.
16.1How Supplied BYETTA (exenatide) Injection is a clear, colorless solution supplied as: • 5 mcg per dose, in a single-patient-use prefilled pen containing 300 mcg/1.2 mL (250 mcg/mL), 60 doses, NDC 0310-6512-01. • 10 mcg per dose, in a single-patient-use prefilled pen containing 600 mcg/2.4 mL (250 mcg/mL), 60 doses, NDC 0310-6524-01.
📦 Storage and Handling ▾
16.2Storage and Handling • Store BYETTA in the refrigerator at 36°F to 46°F (2°C to 8°C). • After first use, BYETTA can be kept at a temperature not to exceed 77°F (25°C). • Do not freeze. Do not use BYETTA if it has been frozen. • Protect BYETTA from light. • Discard the pen 30 days after first use, even if some drug remains in the pen. • Use a puncture-resistant container to discard the needles. Do not reuse or share needles.
📋 Description ▾
11 DESCRIPTION BYETTA (exenatide) is a synthetic peptide, GLP-1 receptor agonist, that was originally identified in the lizard Heloderma suspectum . Exenatide is a 39-amino acid peptide amide. Exenatide has the empirical formula C 184 H 282 N 50 O 60 S and molecular weight of 4186.6 Daltons.
The amino acid sequence for exenatide is shown below. H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH 2 BYETTA injection is supplied for subcutaneous administration as a sterile, preserved isotonic solution in a glass cartridge that has been assembled in a pen-injector (pen). Each milliliter (mL) contains 250 micrograms (mcg) synthetic exenatide, 2.2 mg metacresol as an antimicrobial preservative, mannitol as a tonicity-adjusting agent, and glacial acetic acid and sodium acetate trihydrate in water for injection as a buffering solution at pH 4.5.
Two prefilled pens are available to deliver unit doses of 5 mcg per dose or 10 mcg per dose. Each prefilled pen will deliver 60 doses to provide for 30 days of twice daily administration (BID). Each prefilled device is filled with volume to allow delivery of 1.2 mL or 2.4 mL.
Each device contains additional volume to allow for troubleshooting the device 4 times.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Acute Pancreatitis Inform patients of the potential risk for acute pancreatitis and its symptoms: severe abdominal pain that may radiate to the back, and which may or may not be accompanied by vomiting. Instruct patients to discontinue BYETTA promptly and contact their physician if pancreatitis is suspected [see Warnings and Precautions (5.1) ].
Never Share a BYETTA Pen Between Patients Advise patients that they must never share a BYETTA pen with another person, even if the needle is changed, because doing so carries a risk for transmission of blood-borne pathogens [see Warnings and Precautions (5.2) ]. Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin Inform patients that the risk of hypoglycemia is increased when BYETTA is used in combination with an agent that induces hypoglycemia, such as a sulfonylurea or insulin. Educate patients on the signs and symptoms of hypoglycemia [see Warnings and Precautions (5.3) ].
Acute Kidney Injury Due to Volume Depletion Inform patients of the potential risk of acute kidney injury due to dehydration associated with gastrointestinal adverse reactions. Advise patients to take precautions to avoid fluid depletion. Inform patients of the signs and symptoms of acute kidney injury and instruct them to promptly report any of these signs or symptoms or persistent (or extended) nausea, vomiting, and diarrhea to their healthcare provider [see Warnings and Precautions (5.4) ].
Severe Gastrointestinal Adverse Reactions Inform patients of the potential risk of severe gastrointestinal adverse reactions. Instruct patients to contact their healthcare provider if they have severe or persistent gastrointestinal symptoms [see Warnings and Precautions (5.5) ]. Drug-Induced Thrombocytopenia Inform patients that drug-induced immune mediated thrombocytopenia has been reported during use of exenatide.
Inform patients that if symptoms of thrombocytopenia occur, stop taking BYETTA and seek medical advice promptly [see Warnings and Precautions (5.8) ]. Hypersensitivity Reactions Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of BYETTA. If symptoms of hypersensitivity reactions occur, instruct patients to stop taking BYETTA and seek medical advice promptly [see Warnings and Precautions (5.7) ].
Acute Gallbladder Disease Inform patients of the potential risk for cholelithiasis or cholecystitis. Instruct patients to contact their physician if cholelithiasis or cholecystitis is suspected for appropriate clinical follow-up [see Warnings and Precautions (5.9) ]. Pulmonary Aspiration During General Anesthesia or Deep Sedation Inform patients that BYETTA may cause their stomach to empty more slowly which may lead to complications with anesthesia or deep sedation during planned surgeries or procedures.
Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking BYETTA [see Warnings and Precautions (5.10) ]. Pregnancy Advise patients to inform their physicians if they are pregnant or intend to become pregnant. Instructions Instruct patients to administer BYETTA as a subcutaneous injection in the thigh, abdomen, or upper arm at any time within the 60-minute period before the morning and evening meals (or before the two main meals of the day, approximately 6 hours or more apart).
Do not administer BYETTA after a meal. If a dose is missed, resume the treatment regimen as prescribed with the next scheduled dose. Distributed by: AstraZeneca Pharmaceuticals LP Wilmington, DE 19850 BYETTA ® is a registered trademark of the AstraZeneca group of companies.
💬 Medication Guide ▾
MEDICATION GUIDE BYETTA® (bye-A-tuh) (exenatide) injection, for subcutaneous use Read this Medication Guide and the Instructions for Use that comes with BYETTA before you start using it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking with your healthcare provider about your medical condition or your treatment.
If you have questions about BYETTA after reading this information, ask your healthcare provider or pharmacist. What is the most important information I should know about BYETTA? • Serious side effects can happen in people who take BYETTA, including inflammation of your pancreas (pancreatitis). Stop using BYETTA and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting.
You may feel the pain from your abdomen to your back. What is BYETTA? • BYETTA is an injectable prescription medicine that is used along with diet and exercise to improve blood sugar (glucose) in adults with type 2 diabetes mellitus. • BYETTA is not recommended for people who take exenatide or other medicines called glucagon-like peptide 1 (GLP-1) receptor agonist. • It is not known if BYETTA is safe and effective in children. Who should not use BYETTA?
Do not use BYETTA if: • you have had a severe allergic reaction to exenatide or any of the other ingredients in BYETTA. See the end of this Medication Guide for a complete list of ingredients in BYETTA. See “ What are the possible side effects of BYETTA? ” for symptoms of a serious allergic reaction. • you have a history of low blood platelet count from using exenatide medicines (drug-induced thrombocytopenia).
Before taking BYETTA, tell your healthcare provider about all of your medical conditions, including if you: • have or have had problems with your pancreas. • have severe problems with your stomach, such as delayed emptying of your stomach (gastroparesis) or problems with digesting food. • are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). • are pregnant or plan to become pregnant. It is not known if BYETTA will harm your unborn baby. Tell your healthcare provider if you become pregnant while taking BYETTA.
Talk to your healthcare provider about the best way to control your blood sugar if you plan to become pregnant or while you are pregnant. • are breastfeeding or plan to breastfeed. It is not known if BYETTA passes into your breast milk. You should talk with your healthcare provider about the best way to feed your baby while taking BYETTA.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. BYETTA may affect the way some medicines work and some other medicines may affect the way BYETTA works. Before using BYETTA, talk to your healthcare provider about low blood sugar and how to manage it.
Tell your healthcare provider if you are taking other medicines to treat diabetes, including insulin or sulfonylureas. Especially tell your healthcare provider if you take: • birth control pills that are taken by mouth (oral contraceptives). BYETTA may lower the amount of the medicine in your blood from your birth control pills and they may not work as well to prevent pregnancy.
Take your birth control pills at least one hour before your injection of BYETTA. If you must take your birth control pills with food, take it with a meal or snack at a time when you do not also take BYETTA. • antibiotics. Take antibiotic medicines at least one hour before taking BYETTA.
If you must take your antibiotic with food, take it with a meal or snack at a time when you do not also take BYETTA. • warfarin • lovastatin Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use BYETTA? • Read the Instructions for Use that comes with BYETTA. •…