Generic Name: Exenatide
Class: Incretin Mimetics
Molecular Formula: C184H282N50O60S
CAS Number: 141732-76-5
Special Alerts:
[Posted 11/02/2009] FDA notified healthcare professionals of revisions to the prescribing information for exenatide (Byetta) to include information on post-marketing reports of altered kidney function, including acute renal failure and insufficiency. Exenatide, an incretin-mimetic, is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
From April 2005 through October 2008, FDA received 78 cases of altered kidney function (62 cases of acute renal failure and 16 cases of renal insufficiency), in patients using exenatide. Some cases occurred in patients with pre-existing kidney disease or in patients with one or more risk factors for developing kidney problems. Labeling changes include:
Information regarding post-market reports of acute renal failure and insufficiency, highlighting that exenatide should not be used in patients with severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease.
Recommendations to healthcare professionals that caution should be applied when initiating or increasing doses of exenatide from 5 mcg to 10 mcg in patients with moderate renal impairment (creatinine clearance 30 to 50 ml/min).
Recommendations that healthcare professionals monitor patients carefully for the development of kidney dysfunction, and evaluate the continued need for exenatide if kidney dysfunction is suspected while using the product.
Information about kidney dysfunction in the patient Medication Guide to help patients understand the benefits and potential risks associated with exenatide.
For more information visit the FDA website at: and .
REMS:
FDA approved a REMS for exenatide to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().
Introduction
Antidiabetic agent; synthetic glucagon-like peptide-1 (GLP-1) mimetic (incretin mimetic).1 2 3 4
Uses for Byetta
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Diabetes Mellitus
Used in combination with metformin and/or a sulfonylurea or a thiazolidinedione, as an adjunct to diet and exercise for the management of type 2 (noninsulin dependent) diabetes mellitus (NIDDM).1 Should be added to, not substituted for, metformin, sulfonylurea, or thiazolidinedione therapy.1
Safety and efficacy have not been shown in combination with insulin, d-phenylalanine derivatives, meglitinides, or α-glucosidase inhibitors.1
Byetta Dosage and Administration
Administration
Administer by sub-Q injection using the prefilled injection pen.1 7 No data available on safety or efficacy of IV or IM administration.1
Sub-Q Administration
Administer by sub-Q injection twice daily, prior to (i.e., within 60 minutes of) morning and evening meals.1 7 14
Alternatively, administer before 2 main meals of the day, approximately ≥6 hours apart.1 7 14
Do not administer after a meal.1 7 14
Administer into the abdomen, thigh, or upper arm.1 7
Dosage
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Give in combination with metformin and/or sulfonylurea or thiazolidinedione therapy.1 If used in combination with a sulfonylurea, adjustment of sulfonylurea dosage may be necessary.1 No dosage adjustment is required when used in combination with metformin or a thiazolidinedione.1 (See Specific Drugs under Interactions.)
Adults
Diabetes Mellitus
Sub-Q
Initially, 5 mcg twice daily.1 7 14 If needed, may increase to 10 mcg twice daily after 1 month.1 7
Special Populations
Hepatic Impairment
Dosage adjustment not required.1 14
Renal Impairment
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
No dosage adjustment required in patients with mild to moderate impairment (Clcr 30–80 mL/minute); use not recommended in patients with end-stage renal disease or severe renal impairment (Clcr <30 mL/minute).1 9 12
Geriatric Patients
Careful dosage selection recommended due to possible age-related decrease in renal function and concomitant disease and drug therapy; however, dosage requirements generally similar in geriatric patients and younger adults.1
Obese Patients
Dosage adjustment not required.1
Cautions for Byetta
Contraindications
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Known hypersensitivity to exenatide or any ingredient in the formulation.1
Warnings/Precautions
Sensitivity Reactions
Generalized pruritus and/or urticaria, macular or papular rash, and angioedema reported during postmarketing experience.1 Anaphylactic reaction reported rarely.1
General Precautions
Pancreatitis
Acute pancreatitis reported during postmarketing experience with exenatide.1 17 20
Persistent, severe abdominal pain, which may be accompanied by vomiting, is the hallmark symptom of acute pancreatitis.1
Most patients who developed pancreatitis had at least one other risk factor for acute pancreatitis (e.g., gallstones, severe hypertriglyceridemia, alcohol use) and required hospitalization.17
Potentially fatal hemorrhagic or necrotizing pancreatitis requiring hospitalization reported with exenatide.20
Serious complications include dehydration and renal failure, suspected ileus, phlegmon, and ascites; most patients improved upon discontinuance of exenatide.17
Healthcare providers should be alert for signs and symptoms of acute pancreatitis (e.g., unexplained, severe abdominal pain that may radiate to the back; nausea; vomiting; elevated serum amylase or lipase concentrations).17
If pancreatitis is suspected, therapy with exenatide and other potentially suspected drugs should be discontinued, confirmatory tests performed (e.g., serum amylase or lipase concentrations, radiologic imaging), and appropriate therapy initiated.1 17 20 Patients should be carefully monitored until recovery.20
Exenatide should not be resumed if pancreatitis is confirmed and an alternative etiology for pancreatitis has not been identified.1 17 20
Insulin-Requiring Patients
Not a substitute for insulin in insulin-requiring patients.1
Do not use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.1
Renal Effects
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Deterioration of renal function (e.g., increased Scr, renal impairment, worsened chronic renal failure, acute renal failure sometimes requiring hemodialysis) reported rarely with exenatide.1
Exenatide has not been found to be directly nephrotoxic in preclinical or clinical studies.1
Renal effects usually were reversible with supportive treatment and discontinuance of potentially causative agents, including exenatide.1 (See Renal Impairment under Cautions.)
Hypoglycemia
Possible dose-related hypoglycemia with concomitant sulfonylurea therapy;1 3 5 usually mild-to-moderate in intensity and resolves with oral carbohydrate administration.1 (See Specific Drugs under Interactions.)
No alteration of counterregulatory hormone responses to insulin-induced hypoglycemia reported.1 14 15
GI Effects
Adverse GI effects (e.g., nausea, vomiting, diarrhea) reported commonly.1 Use not recommended in patients with severe GI disease (e.g., gastroparesis).1 14
Immunogenicity
Antibodies to exenatide have developed in patients receiving exenatide therapy; clinical relevance is unknown.1 3 9
Antibody titers diminish over time in most patients.1
Formation of high titers of such antibodies could result in failure of adequate glycemic control.1 If inadequate glycemic control or failure to achieve targeted glycemic control occurs, consider alternative antidiabetic therapy.1
Specific Populations
Pregnancy
Category C.1
Pregnancy registry at 800-633-9081.1
Lactation
Distributed into milk in mice; not known whether distributed into human milk.1 Discontinue nursing or the drug.1
Pediatric Use
Safety and efficacy not established in children <17 years of age.1 14
Geriatric Use
No substantial differences in safety and efficacy nor in pharmacokinetics relative to younger adults.1 9
Hepatic Impairment
Pharmacokinetics not evaluated, but impact of hepatic impairment should be minimal.1 14
Renal Impairment
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Decreased clearance in patients with end-stage renal disease (ESRD) receiving dialysis; possible decreased tolerance to therapy due to adverse GI effects.1 12 Use not recommended in patients with ESRD or severe renal impairment (Clcr <30 mL/minute).1 9
Common Adverse Effects
Nausea, hypoglycemia, vomiting, diarrhea, jittery feeling, dizziness, headache, dyspepsia.1
Interactions for Byetta
Orally Administered Drugs
Possible decreased rate and extent of absorption of concomitantly administered oral drugs; use with caution with oral drugs requiring rapid GI absorption.1
Specific Drugs
Drug | Interaction | Comments |
|---|---|---|
Acetaminophen | Decreased acetaminophen AUC and peak plasma concentrations, delayed time to peak plasma concentrations of acetaminophen1 | Administer acetaminophen ≥1 hour prior to exenatide administration1 11 |
Antidiabetic agents (sulfonylureas) | Increased risk of hypoglycemia1 | Consider dosage reduction of sulfonylurea1 |
Anti-infective agents, oral | Possible decreased rate and extent of anti-infective absorption1 | Administer anti-infective agent ≥1 hour prior to exenatide administration1 9 |
Digoxin | Decreased peak plasma digoxin concentrations and delayed time to peak plasma concentration; no change in steady-state AUC and renal clearance of digoxin9 10 | |
Lisinopril | Delayed time to peak plasma lisinopril concentrations; no change in steady-state AUC or peak plasma lisinopril concentrations 1 9 13 | |
Lovastatin | Decreased lovastatin AUC and peak plasma concentrations and delayed time to peak plasma concentration1 9 | Not associated with consistent changes in lipid profiles compared with baseline1 9 |
Metformin | No increased incidence of hypoglycemia reported1 6 | Dosage adjustments not required1 |
Oral contraceptives | Possible decreased rate and extent of oral contraceptive absorption1 | Administer oral contraceptive ≥1 hour prior to exenatide administration1 9 |
Warfarin | Delayed time to peak plasma concentration of warfarin; no change in AUC or peak plasma warfarin concentrations1 |
Byetta Pharmacokinetics
Manufacturer states pharmacokinetics are independent of dose, age, gender, race, and patient weight.1
Absorption
Bioavailability
Following sub-Q administration, peak plasma concentration usually attained in 2.1 hours.1
Absorption is similar when injected into abdomen, thigh, or arm.1
Distribution
Extent
Distributed into milk in mice; not known whether distributed into human milk.1
Elimination
Metabolism
Primarily proteolytic degradation after glomerular filtration.1
Elimination Route
Excreted principally in urine.1
Half-life
2.4 hours.1
Special Populations
Decreased clearance in patients with end-stage renal disease receiving dialysis.1 Clearance is slightly decreased in patients with mild to moderate renal impairment.1
Stability
Storage
Parenteral
Solution for Injection
Before use, 2–8°C.1 After first use, ≤25ºC.1 Do not freeze; protect from light.1 Discard pen 30 days after first use.1
Actions
A synthetic analog of a naturally occurring peptide isolated from the saliva of Heloderma suspectum (Gila monster); is a glucagon-like peptide-1 (GLP-1) mimetic (incretin mimetic).1 2 3 4 5 6 8
Structurally and pharmacologically unrelated to insulin, sulfonylureas, meglitinides, biguanides, thiazolidinediones, and α-glucosidase inhibitors.1
Lowers fasting and postprandial glucose concentrations in patients with type 2 diabetes mellitus.1 2 3 8
Improves pancreatic β-cell function by increasing glucose-dependent insulin synthesis, secretion and acute β-cell responsiveness (i.e., first phase insulin response).1 2 3 4 8 14
Inhibits inappropriately high glucagon secretion (e.g., after a meal) in patients with type 2 diabetes mellitus1 3 8 but does not impair normal glucagon response to hypoglycemia.1
Slows gastric emptying, which reduces the rate of glucose absorption from a meal and reduces food intake.1 2 5 6 8
Advice to Patients
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Importance of adhering to diet and exercise regimen.1 7 Importance of regular monitoring (preferably self-monitoring) of blood glucose and HbA1c.1 7
Importance of informing patients not to administer the drug after a meal.1 7
Importance of providing patient a copy of manufacturer’s patient information.1 7
Inform patients of the potential risks and advantages of exenatide therapy.1
Importance of appropriate management of hypoglycemia and hyperglycemia, and assessment for other diabetes complications.1 Risk of hypoglycemia in patients receiving concomitant sulfonylurea hypoglycemic therapy.1 Provide instructions regarding management of hypoglycemia, including recognition of symptoms, predisposing conditions, and treatment.1
Risk of nausea, particularly upon initiation of therapy.1 7
Provide instructions regarding proper use and storage of the injection pen and injection technique.1 7 Importance of advising patient that if a dose is missed, resume the treatment regimen as prescribed with the next scheduled dose.1 7
Importance of seeking prompt medical attention if unexplained, persistent, severe abdominal pain with or without nausea and vomiting occurs.1 7 17
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 7
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., GI disease, severe kidney disease).1 7 Advise patients regarding the timing of administration with concomitant oral drugs (e.g., oral contraceptives, anti-infective agents).1 7
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for subcutaneous use | 250 mcg/mL | Byetta (available as prefilled cartridge pen) | Amylin |
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Byetta 10 MCG Pen 10MCG/0.04ML Solution (AMYLIN PHARMACEUTICALS): 2/$281.98 or 7/$825.01
Byetta 5 MCG Pen 5MCG/0.02ML Solution (AMYLIN PHARMACEUTICALS): 1/$313.46 or 4/$868.71
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
1. Amylin Pharmaceuticals. Byetta (exenatide) injection prescribing information. San Diego, CA; 2008 Jun.
2. Scott V, Rodgers PT, Scates AC. Incretin mimetics as emerging treatments for type 2 diabetes. Ann Pharmacother. 2005; 39:110-8. [IDIS 534323] [PubMed 15562141]
3. Buse JB, Henry RR, Hans J et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004; 27:2628-35. [IDIS 534649] [PubMed 15504997]
4. Nuack MA. Glucagon-like peptide (GLP-1): a promising approach and a novel treatment for patients with type 2 diabetes. Int J Clin Pract. S138:45-52.
5. Kendall DM, Riddle MC, Rosenstock J et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005; 28:1083-91. [IDIS 538293] [PubMed 15855571]
6. Defronzo RA, Ratner RE, Han J et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005; 28:1092-100. [IDIS 538294] [PubMed 15855572]
7. Amylin Pharmaceuticals. Byetta (exenatide) injection patient information. San Diego, CA; 2008 Jun.
8. Kolterman OG, Kim DD, Shen L et al. Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health- Syst Pharm. 2005; 62:173-81. [IDIS 538343] [PubMed 15700891]
9. Keating GM. Exenatide. Drugs. 2005; 65(12):1681-92; discussion 1693-5. [PubMed 16060703]
10. Kothare PA, Soon DK, Linnebjerg H et al. Effect of exenatide on the steady-state pharmacokinetics of digoxin. J Clin Pharmacol. 2005; 45(9):1032-7. [PubMed 16100297]
11. Blase E, Taylor K, Gao HY et al. Pharmacokinetics of an oral drug (acetaminophen) administered at various times in relation to subcutaneous injection of exenatide (exendin-4) in healthy subjects. J Clin Pharmacol. 2005; 45(5):570-7. [PubMed 15831781]
12. Linnebjerg H, Hothare P, Park S, et al. Exenatide pharmacokinetics in patients with mild to moderate renal dysfunction and end stage renal disease [abstract no. 469-P]. Diabetes. 2005; 54 (Suppl 1):A116.
13. Kothare P, Linnebjerg H, Atkins M, et al. Effect of exenatide on lisinopril pharmacodynamics in patients treated for hypertension [abstract no. PI-24]. Clin Pharmacol Ther. 2005; 77 (2):P14.
14. Amylin Pharmaceuticals, Inc., San Diego, CA: Personal communication.
15. Degn KB, Brock B, Juhl CB et al. Effect of intravenous infusion of exenatide (synthetic exendin-4) on glucose-dependent insulin secretion and counterregulation during hypoglycemia. Diabetes. 2004; 53:2397-403. [PubMed 15331551]
16. Zinman B, Hoogwerf BJ, Garcia SD et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2007; 146:477-85. [PubMed 17404349]
17. Food and Drug Administration, Center for Drug Evaluation and Research. FDA alert: Information for healthcare professional exenatide (marketed as Byetta). Rockville MD: Food and Drug Administration; 2007 Oct 2. Available from FDA website. Accessed 2007 Nov 2.
18. Jones MC. Therapies for diabetes: pramlintide and exenatide. Am Fam Physician. 2007; 75:1831-5. [PubMed 17619527]
19. Mikhail N. Exenatide: a novel approach for treatment of type 2 diabetes. South Med J. 2006; 99:1271-9. [PubMed 17195423]
20. Food and Drug Administration, Center for Drug Evaluation and Research. FDA alert: Information for healthcare professionals exenatide (marketed as Byetta). Rockville MD: Food and Drug Administration; 2008 Aug 18. Available from FDA website. Accessed 2008 Oct 10.
More Byetta resources
- Byetta Side Effects (in more detail)
- Byetta Use in Pregnancy & Breastfeeding
- Byetta Drug Interactions
- Byetta Support Group
- 50 Reviews for Byetta - Add your own review/rating
Compare Byetta with other medications
- Diabetes, Type 2
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