Saxagliptina

Uses

Monotherapy And Combination Therapy: Saxagliptina is used for an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Limitation Of Use: Saxagliptina is not used for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis, as it would not be effective in these settings.

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

How Saxagliptina works

Saxagliptina is a dipeptidyl peptidase-4 (DPP-4) inhibitor antidiabetic for the treatment of type 2 diabetes. DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver. [Bristol-Myers Squibb Press Release] DPP-4 is a membrane associated peptidase which is found in many tissues, lymphocytes and plasma. DPP-4 has two main mechanisms of action, an enzymatic function and another mechanism where DPP-4 binds adenosine deaminase, which conveys intracellular signals via dimerization when activated. Saxagliptina forms a reversible, histidine-assisted covalent bond between its nitrile group and the S630 hydroxyl oxygen on DPP-4. The inhibition of DPP-4 increases levels active of glucagon like peptide 1 (GLP-1), which inhibits glucagon production from pancreatic alpha cells and increases production of insulin from pancreatic beta cells.

Dosage

Saxagliptina dosage

Recommended Dosage: The recommended dosage of Saxagliptina is 2.5 mg or 5 mg once daily taken regardless of meals. Saxagliptina tablets must not be split or cut.

Dosage In Patients With Renal Impairment: No dosage adjustment for Saxagliptina is recommended for patients with mild renal impairment (CrCl >50 mL/min).

The dosage of Saxagliptina is 2.5 mg once daily (regardless of meals) for patients with moderate or severe renal impairment, or with end-stage renal disease (ESRD) requiring hemodialysis (CrCl ≤ 50 mL/min). Saxagliptina should be administered following hemodialysis. Saxagliptina has not been studied in patients undergoingperitoneal dialysis.

Because the dosage of Saxagliptina should be limited to 2.5 mg based upon renal function, assessment of renal function is recommended prior to initiation of Saxagliptina and periodically thereafter. Renal function can be estimated from serum creatinine using the Cockcroft-Gault formula or Modification of Diet in Renal Disease formula.

Dosage Adjustment With Concomitant Use Of Strong CYP3A4/5 Inhibitors: The dosage of Saxagliptina is 2.5 mg once daily when coadministered with strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitors (e.g., ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin)

Concomitant Use With An Insulin Secretagogue (e.g., Sulfonylurea) Or With Insulin When Saxagliptina is used in combination with aninsulinsecretagogue (e.g.,sulfonylurea) or with insulin, a lower dose of the insulin secretagogue or insulin may be required to minimize the risk ofhypoglycemia

May be taken with or without food.

Side Effects

The following serious adverse reactions are described below or elsewhere in the prescribing information: Pancreatitis, Heart Failure, Hypoglycemia with Concomitant Use of Sulfonylurea or Insulin, Hypersensitivity Reactions, Severe and disabling arthralgia, Bullous pemphigoid

Toxicity

Adverse reactions reported in ≥5% of patients treated with saxagliptin and more commonly than in patients treated with placebo are: upper respiratory tract infection, urinary tract infection, and headache.

Precaution

Moderate and severe renal impairment. Pregnancy and lactation.

Interaction

Increased risk of hypoglycaemia with concomitant sulfonylureas, dose reduction may be necessary. Increased serum levels with CYP3A4/5 inhibitors (e.g. atazanavir, ketoconazole, nefazodone, ritonavir). Concomitant CYP3A4 inducers (e.g. carbamazepine, phenobarbital) may reduce the glycaemic lowering effect of saxagliptin.

Food Interaction

• Take with food. Food increases total drug exposure.

[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.

MANAGEMENT: 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.

Saxagliptina Drug Interaction

Moderate: insulin glargine, furosemide, insulin aspart, budesonide / formoterolUnknown: aspirin, aspirin, ubiquinone, duloxetine, apixaban, omega-3 polyunsaturated fatty acids, atorvastatin, metoprolol, metoprolol, esomeprazole, semaglutide, acetaminophen, clopidogrel, linagliptin, cyanocobalamin, cholecalciferol

Saxagliptina Disease Interaction

Major: pancreatitisModerate: renal dysfunction

Volume of Distribution

151 L

Elimination Route

Following a 5 mg single oral dose of saxagliptin to healthy subjects, the mean plasma AUC values for saxagliptin and its active metabolite were 78 ng•h/mL and 214 ng•h/mL, respectively. The corresponding plasma Cmax values were 24 ng/mL and 47 ng/mL, respectively. Saxagliptina did not accumulate following repeated doses. The median time to maximum concentration (Tmax) following the 5 mg once daily dose was 2 hours for saxagliptin and 4 hours for its active metabolite. Bioavailability, 2.5 - 50 mg dose = 67%

Half Life

Saxagliptina = 2.5 hours; 5-hydroxy saxagliptin = 3.1 hours;

Clearance

Renal clearance, single 50 mg dose = 14 L/h

Elimination Route

Saxagliptina is eliminated by both renal and hepatic pathways. Following a single 50 mg dose of 14C-saxagliptin, 24%, 36%, and 75% of the dose was excreted in the urine as saxagliptin, its active metabolite, and total radioactivity, respectively. A total of 22% of the administered radioactivity was recovered in feces representing the fraction of the saxagliptin dose excreted in bile and/or unabsorbed drug from the gastrointestinal tract.

Pregnancy & Breastfeeding use

Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Contraindication

Type 1 diabetes, diabetic ketoacidosis.

Special Warning

Mild Renal Impairment: No dosage adjustment needed.

Moderate to Severe including with ESRD requiring hemodialysis: 2.5 mg once daily.

Hepatic Impairment No dosage adjustment.

Storage Condition

Store between 20-25° C.

Innovators Monograph

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