Increnat

Uses

Increnat is a GLP-1 agonist used in the management of type 2 diabetes mellitus.

Increnat is indicated for improving glycemic control in adults with type 2 diabetes mellitus along with diet and exercise.

Increnat is also used to associated treatment for these conditions: Type 2 Diabetes Mellitus

How Increnat works

Increnat 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. Increnat also slows gastric emptying and decreases food intake. These effects work synergistically to improve glycemic control by reducing the likelihood of hyper and hypoglycemia.

Toxicity

In animal studies, exenatide was associated with fetal deformities of ribs and vertebrae as well as slowed growth. In humans, uncontrolled hyperglycemia can be associated with an up to 25% risk of miscarriage. 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 risks. 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 humans. The effect of exenatide on breastfed infants is also unknown and so the risk and benefit of breastfeeding while taking exenatide must be weighed. There is no data for the use of exenatide in pediatric patients. 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 effects. 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 cautiously. Increnat is not recommended for patients with creatinine clearance Label. Hepatic impairment is not expected to affect clearance of exenatide though no studies have been performed to confirm this.

Food Interaction

• Take before a meal. Inject subcutaneously within 60 minutes before morning and evening meals.

[Moderate] ADJUST DOSING INTERVAL: Increnat slows gastric emptying and may reduce the extent and rate of absorption of concomitantly administered oral medications.

When acetaminophen 1000 mg was administered simultaneously with exenatide 10 mcg and also one hour, 2 hours, and 4 hours after exenatide injection, acetaminophen systemic exposure (AUC) was decreased by 21%, 23%, 24%, and 14%, respectively; peak plasma concentration (Cmax) was decreased by 37%, 56%, 54%, and 41%, respectively; and time to peak plasma concentration (Tmax) was increased from 0.6 hours in the control period to 0.9 hours, 4.2 hours, 3.3 hours, and 1.6 hours, respectively.

These values were not significantly changed when acetaminophen was given one hour before exenatide injection.

MANAGEMENT: Concomitantly administered oral medications that are dependent on threshold concentrations for efficacy (e.g., antibiotics, contraceptives) or that require rapid gastrointestinal absorption (e.g., hypnotics, pain medications) should be administered at least 1 hour before exenatide.

If such medications are to be administered with food, patients should be advised to take them with a meal or snack when exenatide is not administered.

Increnat Alcohol interaction

[Moderate] GENERALLY AVOID:

Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes.

Hypoglycemia most frequently occurs during acute consumption of alcohol.

Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise.

The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia.

Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion.

By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia.

[Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes.

A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis.

Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan.

Alcohol should not be consumed on an empty stomach or following exercise.

Increnat Drug Interaction

Moderate: insulin lispro, insulin lispro, insulin glargine, insulin glargine, insulin glargine, insulin glargineUnknown: ubiquinone, ubiquinone, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, sitagliptin, sitagliptin, empagliflozin, empagliflozin, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol

Increnat Disease Interaction

Major: severe renal impairment, pancreatitis, thyroid carcinomaModerate: renal dysfunction

Volume of Distribution

28.3L.

Elimination Route

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

Half Life

2.4 hours

Clearance

9.1 L/hour.

Elimination Route

Increnat is mainly eliminated by glomerular filtration followed by proteolysis before finally being eliminated in the urine.

Innovators Monograph

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