Drug information of Exenatide

Exenatide


Exenatide is a glucagon-like peptide-1 (GLP-1) analog. It functions to activate the GLP-1 receptor and increases insulin secretion, decrease glucagon secretion, and slow gastric emptying to improve glycemic control.

Mechanism of effect

Exenatide is a human glucacon-like peptide-1(GLP-1) receptor agonist. By activating this receptor, insulin secretion is increased and glucagon secretion is decreased in a glucose dependant manner. Exenatide also slows gastric emptying and decreases food intake. These effects work synergistically to improve glycemic control by reducing the likelihood of hyper and hypoglycemia.

Pharmacodynamic

When patients take exenatide the body's natural response to glucose is modulated. More insulin and less glucagon are released in response to glucose, though in cases of hypoglycemia a normal amount of glucagon is released. Exenatide also slows gastric emptying, leading to a slower and prolonged release of glucose into the systemic circulation. Together these effects prevent hyper and hypoglycemia.

Pharmacokinetics

Absorption: Exenatide reaches a peak plasma concentration in 2.1 hours. Because exenatide is administerd subcutaneously, the bioavailability is 1.

Volume of distribution: 28.3L.

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 exenatide. Exenatide is metabolised to small peptides <3 amino acids in length by enzymes in the kidney.

Route of elimination: urine

Half life: 2.4 hours

Clearance: 9.1 L/hour

Dosage

Usual Adult Dose for Diabetes Type 2

Immediate release: Initial: 5 mcg twice daily within 60 minutes prior to morning and evening meals (or before the two main meals of the day, ≥6 hours apart); after 1 month, may be increased to 10 mcg twice daily (based on response).

Extended release: 2 mg once weekly at any time of day, with or without meals

Safety and efficacy have not been established in patients younger than 18 years.

Alerts

  • Anti-exenatide antibodies: Use may be associated with the development of anti-exenatide antibodies. Low titers are not associated with a loss of efficacy; however, high titers (observed in 6% to 12% of patients in clinical studies) may result in an attenuation of response.
  • Hypersensitivity: Serious hypersensitivity reactions (eg, anaphylaxis, angioedema) have been reported; discontinue therapy in the event of a hypersensitivity reaction. Serious injection-site reactions (eg, abscess, cellulitis, necrosis), with or without subcutaneous nodules have been reported with use. Isolated cases required surgical intervention.
  • Gallbladder disease: Cases of cholelithiasis and cholecystitis have been reported; gallbladder studies and further clinical assessment are indicated if cholelithiasis is suspected.
  • GI symptoms: Most common reactions are GI related; these symptoms may be dose-related and may decrease in frequency/severity with gradual titration and continued use.
  • Pancreatitis: Cases of acute pancreatitis (including hemorrhagic and necrotizing with some fatalities) have been reported; monitor for signs and symptoms of pancreatitis (eg, persistent severe abdominal pain that may radiate to the back, and that may or may not be accompanied by vomiting). Prior to initiating therapy, consider other factors associated with pancreatitis that may be present (eg, hypertriglyceridemia, ethanol abuse, cholelithiasis); it is unknown if exenatide increases the risk for pancreatitis in these patients. If pancreatitis is suspected, discontinue use. Do not resume unless an alternative etiology of pancreatitis is confirmed. Consider alternative antidiabetic therapy in patients with a history of pancreatitis.
  • Renal effects: Cases of acute renal failure and chronic renal failure exacerbation, including severe cases requiring hemodialysis or kidney transplantation, have been reported. May cause nausea/vomiting/diarrhea with transient hypovolemia that can worsen renal function. Renal dysfunction was usually reversible with appropriate corrective measures, including discontinuation of exenatide. Risk may be increased in patients receiving concomitant medications affecting renal function and/or hydration status.
  • Thyroid tumors: Thyroid C-cell tumors have developed in animal studies with exenatide ER; it is not known if exenatide ER causes thyroid C-cell tumor, including medullary thyroid carcinoma (MTC) in humans. Patients should be counseled on the potential risk of MTC with the use of exenatide and informed of symptoms of thyroid tumors (eg, neck mass, dysphagia, dyspnea, persistent hoarseness). Use of exenatide ER is contraindicated in patients with a personal or a family history of medullary thyroid cancer and in patients with multiple endocrine neoplasia syndrome type 2 (MEN2).

Points of recommendation

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use exenatide in larger or smaller amounts or for longer than recommended.

Do not use Exenatide  after eating a meal.

Never share an injection pen, cartridge, or syringe with another person, even if the needle has been changed. Sharing these devices can allow infections or disease to pass from one person to another.

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, irritability, dizziness, nausea, fast heart rate, and feeling anxious or shaky. To quickly treat low blood sugar, always keep a fast-acting source of sugar with you such as fruit juice, hard candy, crackers, raisins, or non-diet soda.

Your doctor can prescribe a glucagon emergency injection kit to use in case you have severe hypoglycemia and cannot eat or drink. Be sure your family and close friends know how to give you this injection in an emergency.

Also watch for signs of high blood sugar (hyperglycemia) such as increased thirst or urination, blurred vision, headache, and tiredness.

Blood sugar levels can be affected by stress, illness, surgery, exercise, alcohol use, or skipping meals. Ask your doctor before changing your dose or medication schedule.

Exenatide  is only part of a complete treatment program that may also include diet, exercise, weight control, regular blood sugar testing, and special medical care. Follow your doctor's instructions very closely.

Storing unopened (not in use) Exenatide : Keep the medicine in its original container. Refrigerate and use until expiration date. Protect from light.

Do not freeze Exenatide , and throw away the medicine if it has been frozen.

Storing opened (in use) Exenatide : Store at room temperature and use within 30 days. Protect from heat and bright light. Do not store the injection pen with a needle attached.

Use the missed dose as soon as you remember, but only if you have not yet eaten a meal. Skip the missed dose if you have already eaten a meal, or if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.


Ask a Pharmacist


User's questions
    No comments yet.