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| Primary information |
|---|
| ID | 10505 |
| Therapeutic ID | Th1098 |
| Protein Name | Exenatide |
| Sequence | >Th1098_Exenatide
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS
|
| Molecular Weight | 4186.6 |
| Chemical Formula | C184H282N50O60S |
| Isoelectric Point | 4.86 |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Mean terminal half-life is 2.4 hours. |
| Description | Derived from a compound found in the saliva of the Gila monster, a large lizard native to the southwestern United States. It is a functional analog of Glucagon-Like Peptide-1 (GLP-1) peptide. |
| Indication/Disease | Indicated as adjunctive therapy to improve glycemic control in patients with Type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of both, but have not achieved adequate glycemic control. |
| Pharmacodynamics | Exenatide is an incretin mimetic, which has glucoregulatory effects. While it is has blood-sugar lowering actions alone, it can also be combined with other medications such as pioglitazone, metformin, sulfonylureas, and/or insulin to improve glucose control. The approved use of exenatide is with either sulfonylureas, metformin and thiazolinediones. The medication is injected twice per day using a pre-filled pen device. Typical human responses to exenatide plus eating include improvements in the initial rapid release of endogenous insulin, suppression of glucagon release by the pancreas, regulation of gastric empyting and reduced appetite; all behaviors more typical of individuals without blood sugar control problems. Exenatide is self-regulating in that in lowers blood sugar when levels are elevated but does not continue to lower blood sugar when levels return to normal, unlike with sulfonylureas or insulins. |
| Mechanism of Action | Exenatide is a functional analog of the human incretin Glucagon-Like Peptide-1 (GLP-1). Incretins enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. The GLP-1 system increases insulin secretion only in the presence of elevated plasma glucose levels, avoiding inappropriately high insulin levels during fasting. The drug also moderates peak serum glucagon levels during hyperglycemic periods following meals, but does not interfere with glucagon release in response to hypoglycemia. Secondary effects of drug administration reduces the rate of gastric emptying and decreases food intake, mitigating the potential severity of hyperglycemic events after meals. |
| Toxicity | In animal studies, exenatide was associated with fetal deformities of ribs and vertebrae as well as slowed growthLabel. In humans, uncontrolled hyperglycemia can be associated with an up to 25% risk of miscarriageLabel. No human studies in pregnancy have been performed with exenatide and so exenatide should only be prescribed in pregnancy if the benefit to the mother and fetus outweigh the risksLabel. In mice, exenatide is excreted in the milk at a concentration 2.5% of the plasma concentration though this data may not be applicable to humansLabel. The effect of exenatide on breastfed infants is also unknown and so the risk and benefit of breastfeeding while taking exenatide must be weighedLabel. There is no data for the use of exenatide in pediatric patientsLabel. Geriatric patients do not have different results for safety and efficacy of exenatide though caution should still be used in this group as they are at higher risk of renal impairment or other comorbidities that may affect the liklihood of adverse effectsLabel. No dosage adjustments are necessary for patients with creatinine clearance ≥50mL/min, though prescribing to patients with creatinine clearance 30-50mL/min should be done cautiouslyLabel. Exenatide is not recommended for patients with creatinine clearance <30mL/minLabel. Hepatic impairment is not expected to affect clearance of exenatide though no studies have been performed to confirm thisLabel. |
| Metabolism | Exenatide is filtered through the glomerulus before being degraded to smaller peptides and amino acids by dipeptidyl peptidase-4, metalloproteases, endopeptidase 24-11, amino proteases, and serine proteases. It is currently believed that the metalloproteases are responsible for most of the degradation of exenatide3. Exenatide is metabolised to small peptides <3 amino acids in length by enzymes in the kidney |
| Absorption | Exenatide reaches a peak plasma concentration in 2.1 hoursLabel. Because exenatide is administerd subcutaneously, the bioavailability is 1 |
| 28.3 L |
| Clearance | Apparent cl=9.1 L/hr |
| Categories | Hypoglycemic Agents |
| Patents Number | US6872700 |
| Date of Issue | 29-Mar-2005 |
| Date of Expiry | 29-Mar-2005 |
| Drug Interaction | NA |
| Target | Glucagon-like peptide 1 receptor |
| Brand Name | BYETTA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | BYETTA (exenatide injection) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. |
| Chemical Name | NA |
| Formulation | BYETTA (exenatide injection) is supplied for SC injection 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 or 10 mcg. Each prefilled pen will deliver 60 doses to provide for 30 days of twice daily administration (BID). |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | BYETTA (exenatide injection) should be initiated at 5 mcg administered 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). BYETTA (exenatide injection) should not be administered after a meal. Based on clinical response, the dose of BYETTA (exenatide injection) can be increased to 10 mcg twice daily after 1 month of therapy. Initiation with 5 mcg reduces the incidence and severity of gastrointestinal side effects. Use BYETTA (exenatide injection) only if it is clear, colorless and contains no particles. |
| Contraindication | BYETTA (exenatide injection) is not a substitute for insulin. BYETTA (exenatide injection) should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings. The concurrent use of BYETTA (exenatide injection) with insulin has not been studied and cannot be recommended.Based on postmarketing data BYETTA (exenatide injection) has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. BYETTA (exenatide injection) has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using BYETTA (exenatide injection) . Other antidiabetic therapies should be considered in patients with a history of pancreatitis. |
| Side Effects | Severe allergic reactions include severe rash or itching, swelling of your face, lips, and throat that may cause difficulty breathing or swallowing, feeling faint or dizzy and very rapid heartbeat. Inflammation of the pancreas (pancreatitis) may happen, which may be severe and lead to death. Your risk for getting low blood sugar (hypoglycemia) is higher. Signs and symptoms of low blood sugar may include headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, fast heartbeat, sweating, and feeling jittery. |
| Useful Link 1 | NA |
| Useful Link 2 | NA |
| Remarks | NA |