Inside BCise

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF THYROID C-CELL TUMORS

  • Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON BCise causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of exenatide extended-release-induced rodent thyroid C-cell tumors has not been determined
  • BYDUREON BCise is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with the use of BYDUREON BCise and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for detection of MTC in patients treated with BYDUREON BCise

CONTRAINDICATIONS

  • Personal or family history of MTC, patients with MEN 2
  • Prior serious hypersensitivity reactions to exenatide or product components

WARNINGS AND PRECAUTIONS

  • Acute Pancreatitis including fatal and non-fatal hemorrhagic or necrotizing pancreatitis has been reported. After initiation, observe patients carefully for symptoms of pancreatitis. If suspected, discontinue promptly and do not restart if confirmed. Consider other antidiabetic therapies in patients with a history of pancreatitis
  • Hypoglycemia Risk of hypoglycemia is increased when exenatide is coadministered with insulin or insulin secretagogues. Consider lowering the dose of these agents when coadministered with BYDUREON BCise
  • Acute Kidney Injury and Impairment of Renal Function Altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation have been reported. Not recommended in patients with severe renal impairment or end-stage renal disease. Use caution in patients with renal transplantation or moderate renal impairment
  • Gastrointestinal Disease Because exenatide is commonly associated with gastrointestinal adverse reactions, not recommended in patients with severe gastrointestinal disease (eg, gastroparesis)
  • Immunogenicity Patients may develop antibodies to exenatide. Patients with higher titer antibodies may have an attenuated HbA1c response. In clinical trials, attenuated glycemic response was associated with BYDUREON BCise-treated patients. If worsening of or failure to achieve adequate glycemic control occurs, consider alternative antidiabetic therapy
  • Hypersensitivity Reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema). If this occurs, patients should discontinue BYDUREON BCise and promptly seek medical advice
  • Injection-Site Reactions Serious reactions (eg, abscess, cellulitis, and necrosis), with or without subcutaneous nodules, have been reported
  • Macrovascular Outcomes No clinical studies establishing conclusive evidence of macrovascular risk reduction with exenatide

ADVERSE REACTIONS

Most common (≥5%) in clinical trials: injection-site nodule (10.5%), nausea (8.2%).

DRUG INTERACTIONS

  • Oral Medications BYDUREON BCise slows gastric emptying and may reduce the rate of absorption of orally administered drugs
  • Warfarin Increased international normalized ratio (INR) sometimes associated with bleeding has been reported with concomitant use of exenatide with warfarin. Monitor INR frequently until stable upon initiation of BYDUREON BCise

PREGNANCY

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

INDICATION AND LIMITATIONS OF USE

BYDUREON BCise is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
  • Not recommended as first-line therapy for patients inadequately controlled on diet and exercise
  • Not a substitute for insulin. Should not be used to treat type 1 diabetes or diabetic ketoacidosis
  • Not recommended for use with insulin
  • Do not coadminister with other exenatide-containing products
  • Not studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis

Discover What’s Inside

BYDUREON BCise

FOR ADULTS WITH TYPE 2 DIABETES UNCONTROLLED ON ONE OR MORE ORAL ANTIDIABETIC AGENTS

Dramatization

Unlike other GLP-1 RAs, BYDUREON BCise has a unique continuous-release delivery system.1

Dramatization

Featuring the innovation of microsphere technology1 shown here, inside the BYDUREON BCise device

Dramatization

Each microsphere is approximately 60 microns in size1…the diameter of a human hair

Dramatization

Containing exenatide within a biodegradable polymer matrix1 similar to that used in dissolvable sutures

Dramatization

Once injected, the microspheres containing exenatide aggregate, and initial diffusion of surface exenatide occurs1

Dramatization

The microspheres continue to degrade over time, allowing for the continuous release of exenatide1,2

IMPORTANT SAFETY INFORMATION

open isi

WARNING: RISK OF THYROID C-CELL TUMORS

  • Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON (exenatide extended-release) or BYDUREON BCise (exenatide extended-release) cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of exenatide extended-release-induced rodent thyroid C-cell tumors has not been determined

  • BYDUREON and BYDUREON BCise are contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with the use of BYDUREON or BYDUREON BCise and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for detection of MTC in patients treated with BYDUREON or BYDUREON BCise

CONTRAINDICATIONS

  • For BYDUREON and BYDUREON BCise: Personal or family history of MTC, patients with MEN 2

  • Prior serious hypersensitivity reactions to exenatide or product components

WARNINGS AND PRECAUTIONS

  • Acute Pancreatitis including fatal and non-fatal hemorrhagic or necrotizing pancreatitis has been reported. After initiation, observe patients carefully for symptoms of pancreatitis. If suspected, discontinue promptly and do not restart if confirmed. Consider other antidiabetic therapies in patients with a history of pancreatitis

  • Never Share Injection Device or Needle Between Patients Sharing poses a risk for transmission of blood-borne pathogens, even if the needle is changed

  • Hypoglycemia Risk of hypoglycemia is increased when exenatide is coadministered with insulin or insulin secretagogues. Consider lowering the dose of these agents when coadministered with BYDUREON, BYDUREON BCise or BYETTA (exenatide)

  • Acute Kidney Injury and Impairment of Renal Function Altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation have been reported. Not recommended in patients with severe renal impairment or end-stage renal disease. Use caution in patients with renal transplantation or moderate renal impairment

  • Gastrointestinal Disease Because exenatide is commonly associated with gastrointestinal adverse reactions, not recommended in patients with severe gastrointestinal disease (eg, gastroparesis)

  • Immunogenicity Patients may develop antibodies to exenatide. Patients with higher titer antibodies may have an attenuated HbA1c response. In clinical trials, attenuated glycemic response was associated with BYDUREON-, BYDUREON BCise-, or BYETTA-treated patients. If worsening of or failure to achieve adequate glycemic control occurs, consider alternative antidiabetic therapy

  • Hypersensitivity Reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema). If this occurs, patients should discontinue BYDUREON, BYDUREON BCise or BYETTA and promptly seek medical advice

  • Injection-Site Reactions Serious reactions (eg, abscess, cellulitis, and necrosis), with or without subcutaneous nodules, have been reported with extended-release exenatide

  • Macrovascular Outcomes No clinical studies establishing conclusive evidence of macrovascular risk reduction with exenatide

ADVERSE REACTIONS

  • Most common (=5%) and occurring more frequently than comparator in BYDUREON clinical trials: nausea (16.9%), diarrhea (12.7%), headache (8.0%), vomiting (6.8%), constipation (5.9%), injection-site pruritus (5.9%), injection-site nodule (5.3%), dyspepsia (5.1%)

  • Most common (=5%) in BYDUREON BCise clinical trials: injection-site nodule (10.5%), nausea (8.2%)

  • Most common (=5%) and occurring more frequently than placebo in BYETTA clinical trials: nausea (8%-44%), hypoglycemia (3.8%-35.7%), vomiting (4%-18%), diarrhea (6%-18%), feeling jittery (9%), dizziness (9%), headache (9%-14%), dyspepsia (3%-7%), constipation (10%), asthenia (4%-5%)

DRUG INTERACTIONS

  • Oral Medications BYDUREON, BYDUREON BCise and BYETTA slow gastric emptying and may reduce the rate of absorption of orally administered drugs

  • Warfarin Increased international normalized ratio (INR) sometimes associated with bleeding has been reported with concomitant use of exenatide with warfarin. Monitor INR frequently until stable upon initiation of BYDUREON, BYDUREON BCise, or BYETTA

PREGNANCY

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

INDICATION AND LIMITATIONS OF USE

BYDUREON, BYDUREON BCise and BYETTA are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

  • BYDUREON or BYDUREON BCise is not recommended as first-line therapy for patients inadequately controlled on diet and exercise

  • BYDUREON, BYDUREON BCise or BYETTA is not a substitute for insulin. Should not be used to treat type 1 diabetes or diabetic ketoacidosis

  • BYDUREON and BYETTA have not been studied with prandial insulin. BYDUREON BCise is not recommended for use with insulin

  • Do not coadminister with other exenatide-containing products

  • Not studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis

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Abbreviation: GLP-1 RA, glucagon-like peptide-1 receptor agonist.

References:

  1. BYDUREON® BCise® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. Data on file, REF-14053. AstraZeneca Pharmaceuticals LP.

Abbreviations: FDA, US Food and Drug Administration; GLP-1 RA, glucagon-like peptide-1 receptor agonist.

References:

  1. BYETTA® ([exenatide] injection) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2015.

  2. BYDUREON® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.

  3. BYDUREON® BCise® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  4. Data on file, REF-14053. AstraZeneca Pharmaceuticals LP.

  5. Data on file, REF-33646. AstraZeneca Pharmaceuticals LP.

  6. Data on file, US-20428. AstraZeneca Pharmaceuticals LP.

Abbreviation: GLP-1 RA, glucagon-like peptide-1 receptor agonist.

References:

  1. Bunck MC, Diamant M, Cornér A, et al. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care. 2009;32(5):762-768.

  2. Bunck MC, Corner A, Eliasson B, et al. Effects of exenatide on measures of beta-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care. 2011;34(9):2041-2047.

  3. DeFronzo RA. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58(4):773-795.

  4. BYDUREON® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.

  5. BYETTA® ([exenatide] injection) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2015.

  6. Van Bloemendaal L, IJzerman RG, Ten Kulve JS, et al. GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans. Diabetes. 2014;63(12):4186-4196.

  7. Larsson H, Holst JJ, Ahrén B. Glucagon-like peptide-1 reduces hepatic glucose production indirectly through insulin and glucagon in humans. Acta Physiol Scand. 1997;160(4):413-422.

  8. Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013;17(6):819-837.

  9. DeFronzo RA, Eldor R, Abdul-Ghani M. Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes. Diabetes Care. 2013;36(suppl 2):S127-S138.

  10. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2018 executive summary. Endocr Pract. 2018;24(1):91-120.

  11. Aronoff SL, Berkowitz K, Shreiner B, Want L. Glucose metabolism and regulation: beyond insulin and glucagon. Diabetes Spectrum. 2004;17(3):183-190.

  12. Prasad-Reddy L, Isaacs D. A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond. Drugs Context. 2015;4:212283. doi:10.7573/dic.212283. Accessed April 19, 2018.

Abbreviations: BL, baseline; GLP-1 RA, glucagon-like peptide-1 receptor agonist; PK, pharmacokinetic.

References:

  1. BYDUREON® BCise® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. Data on file, REF-14053. AstraZeneca Pharmaceuticals LP.

Abbreviations: BID, twice daily; BL, baseline; GLP-1 RA, glucagon-like peptide-1 receptor agonist; ITT, intent-to-treat; QW, once weekly; SU, sulfonylurea; TZD, thiazolidinedione.

References:

  1. DeYoung MB, MacConell L, Sarin V, Trautmann M, Herbert P. Encapsulation of exenatide in poly-(D,L-lactide-co-glycolide) microspheres produced an investigational long-acting once-weekly formulation for type 2 diabetes. Diabetes Technol Ther. 2011;13(11):1145-1154.

  2. Data on file, REF-19541. AstraZeneca Pharmaceuticals LP.

Abbreviations: FPG, fasting plasma glucose; GLP-1 RA, glucagon-like peptide-1 receptor agonist; PK, pharmacokinetic; SE, standard error.

References:

  1. BYDUREON® BCise® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. Data on file, REF-19541. AstraZeneca Pharmaceuticals LP.

  3. Data on File, REF-33652. AstraZeneca Pharmaceuticals LP.

  4. Wysham CH, Rosenstock J, Vetter M, Dong F, Öhman P, Iqbal N. Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes. Diabetes Obes Metab. 2018;20(1):165-172.

Abbreviations: BID, twice daily; BL, baseline; ITT, intent-to-treat; QD, once daily; QW, once weekly; SU, sulfonylurea; TZD, thiazolidinedione.

References:

  1. BYDUREON® BCise® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. Data on file, REF-22126. AstraZeneca Pharmaceuticals LP.

  3. Diamant M, Van Gaal L, Stranks S, et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010;375(9733):2234-2243.

  4. Bergenstal RM, Wysham C, MacConell L, et al; for the DURATION-2 Study Group. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010;376(9739):431-439.

  5. Russell-Jones D, Cuddihy RM, Hanefeld M, et al; on behalf of the DURATION-4 Study Group. Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): a 26-week double-blind study. Diabetes Care. 2012;35(2):252-258.

  6. Blevins T, Pullman J, Malloy J, et al. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011;96(5):1301-1310.

  7. Gadde KM, Vetter ML, Iqbal N, et al. DURATION-NEO-2 study investigators. Efficacy and safety of autoinjected exenatide once-weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: the DURATION-NEO-2 randomized clinical study. Diabetes Obes Metab. 2017;19(7):979-988.

  8. Wysham CH, Rosenstock J, Vetter M, Dong F, Öhman P, Iqbal N. Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes. Diabetes Obes Metab. 2018;20(1):165-172.

Abbreviations: AE, adverse event; BID, twice daily; ITT, intent-to-treat; QW, once weekly; SU, sulfonylurea; TZD, thiazolidinedione.

References:

  1. Data on file, US-20428. AstraZeneca Pharmaceuticals LP.

  2. BYDUREON® BCise® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  3. DeYoung MB, MacConell L, Sarin V, Trautmann M, Herbert P. Encapsulation of exenatide in poly-(D,L-lactide-co-glycolide) microspheres produced an investigational long-acting once-weekly formulation for type 2 diabetes. Diabetes Technol Ther. 2011;13(11):1145-1154.

  4. BYDUREON® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.

  5. Data on file, REF-5087. AstraZeneca Pharmaceuticals LP.

  6. Wysham CH, Rosenstock J, Vetter M, Dong F, Öhman P, Iqbal N. Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes. Diabetes Obes Metab. 2018;20(1):165-172.

References:

  1. BYDUREON® BCise® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. Data on file, REF-14053. AstraZeneca Pharmaceuticals LP.

Abbreviations: CGM, continuous glucose monitoring; FPG, fasting plasma glucose; MET, metformin; mITT, modified intent-to-treat; MXR, metformin extended-release; PPG, postprandial glucose.

References:

  1. Data on file, REF-5039. AstraZeneca Pharmaceuticals LP.

  2. Frias JP, Nakhle S, Ruggles JA, et al. Exenatide once weekly improved 24-hour glucose control and reduced glycaemic variability in metformin-treated participants with type 2 diabetes: a randomized, placebo-controlled trial [published online ahead of print August 16, 2016]. Diabetes Obes Metab. doi:10.1111/dom.12763.

Abbreviations: BL, baseline; IG, insulin glargine; LS, least squares; MET, metformin; SU, sulfonylurea; TZD, thiazolidinediones.

References:

  1. BYDUREON® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.

  2. Diamant M, Van Gaal L, Stranks S, et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010;375(9733):2234-2243.

  3. Frías JP, Guja C, Hardy E, et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2016;4(12):1004-1016.

Abbreviations: BID, twice daily; IU, international unit; QW, once weekly.

References:

  1. BYDUREON® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.

  2. Data on file, REF-7842. AstraZeneca Pharmaceuticals LP.

  3. Drucker DJ, Buse JB, Taylor K, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008;372(9645):1240-1250.

  4. Wysham CH, Philis-Tsimikas A, Klein EJ, et al. DURATION-1 extension in patients with type 2 diabetes: efficacy and tolerability of exenatide once weekly over 7 years [poster]. Presented at: 76th Annual Scientific Sessions of American Diabetes Association; June 10-14, 2016; New Orleans, LA. Poster 1041-P.

  5. Diamant M, Van Gaal L, Guerci B, et al. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial. Lancet Diabetes Endocrinol. 2014;2(6):464-473.

  6. Data on file, REF-5090. AstraZeneca Pharmaceuticals LP.

  7. Data on file, REF-4977. AstraZeneca Pharmaceuticals LP.

Abbreviations: PK, pharmacokinetics.

Reference:

  1. BYDUREON® ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.

Abbreviation: GF, glucose fluctuation.