Dapagliflozina

Uses

Dapagliflozina is used for an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

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

How Dapagliflozina works

Dapagliflozina inhibits the sodium-glucose contransporter 2(SGLT2) which is primarily located in the proximal tubule of the nephron. SGLT2 facilitates 90% of glucose resorption in the kidneys and so its inhibition allows for glucose to be excreted in the urine. This excretion allows for better glycemic control and potentially weight loss in patients with type 2 diabetes mellitus.

Dosage

Dapagliflozina dosage

5 mg orally once a day.May increase to 10 mg orally once a day in patients tolerating therapy with 5 mg and requiring additional glycemic control

Side Effects

Renal impairment, Female genital mycotic infections, Urinary tract infection, Increased urination, Male genital mycotic infections, Dyslipidemia, Constipation, Discomfort with urination, Extremity pain, Volume depletion, Hypersensitivity

Toxicity

Age, gender, race, and body weight do not affect dapagliflozin dosing requirements. Although age does not affect dosing requirements, safety has not been established in pediatric populations and patients at an especially advanced age may be more susceptible to adverse effects. Animal studies in pregnancy showed no fetal toxicity in the first trimester but exposure later in pregnancy was associated with renal pelvic dilatation and maternal toxicity at much higher doses than the maximum recommended human dose. Due to this data, dapagliflozin is not recommended in the second and third trimester of pregnancy. Dapagliflozina is excreted in milk from rats, though this may not necessarily be the case in humans. Children under 2 years old who are exposed to dapagliflozin may be at risk of improper kidney development. Dapagliflozina is not recommended in patients with a creatinine clearance below 45mL/min and is contraindicated in patients with creatinine clearance below 30mL/min. Dose adjustments are not necessary in patients with hepatic impairment at any stage, although the risk and benefit to the patient must be assessed as there is limited data on dapagliflozin use in this population.

Precaution

CV disease, history of hypotension, UTI, Children, Elderly. Unknown whether distributed in human breast milk; breastfeeding women should discontinue dapagliflozin or nursing taking into account the importance of the drug to the mother

Interaction

Hypoglycemia may occur with concomitant use with insulin & insulin secretagogues eg sulfonylureas. Decrease in Cmax & AUC with rifampin. Increase in Cmax & AUC with mefenamic acid. Increased thiazide & loop diuretic effects; may increase risk of dehydration & hypotension. Pioglitazone.

Food Interaction

• Avoid excessive or chronic alcohol consumption. Binge drinking or drinking alcohol often may predispose patients to ketoacidosis.
• Take with or without food.

[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.

Dapagliflozina Drug Interaction

Moderate: sacubitril / valsartan, insulin glargine, metoprolol, metoprolol, insulin degludecUnknown: aspirin, aspirin, amoxicillin / clavulanate, rosuvastatin, apixaban, metformin / sitagliptin, sitagliptin, atorvastatin, pregabalin, semaglutide, acetaminophen, clopidogrel, cyanocobalamin, ascorbic acid, cholecalciferol

Dapagliflozina Disease Interaction

Major: liver dysfunction, renal dysfunctionModerate: hypotension, infections

Volume of Distribution

118L.

Elimination Route

Oral dapagliflozin reaches a maximum concentration within 1 hour of administration when patients have been fasting. When patients have consumed a high fat meal, the time to maximum concentration increases to 2 hours and the maximum concentration decreases by half though a dose adjustment is not necessary. Oral dapagliflozin is 78% bioavailable.

Half Life

13.8h.

Clearance

Oral plasma clearance was 4.9 mL/min/kg, and renal clearance was 5.6 mL/min.

Elimination Route

75.2% of dapagliflozin is recovered in the urine with 1.6% of the dose unchanged by metabolism. 21% of the dose is excreted in the feces with 15% of the dose unchanged by metabolism.

Pregnancy & Breastfeeding use

Pregnancy Category-C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks

Contraindication

Hypersensitivity to dapagliflozin propanediol or to any of the excipients. Moderate to severe renal impairment; end-stage renal disease; active bladder cancer. Pregnancy (2nd & 3rd trimester) & lactation.

Special Warning

Renal Impairment: No dosage adjustment is indicated based on renal function. The efficacy is dependent on renal function. lt is not recommended for use in patients with moderate to severe renal impairment (patients with CrCI <60 mL/min or eGFR <60 mL/min/1.73 m2).

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