Drug information of Dapagliflozin

Mechanism of effect

Dapagliflozin 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.

Pharmacodynamic

Dapagliflozin 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.

Pharmacokinetics

Bioavailability: 78%

Peak plasma time: 2 hr (fasting); ~3 hr (with high fat meal)

High fat meal decreases peak plasma concentration by up to 50%

Protein bound: 91%

Metabolism

Metabolism primarily mediated by UGT1A9

CYP-mediated metabolism is a minor clearance pathway in humans

Extensively metabolized, primarily to yield dapagliflozin 3-O-glucuronide (inactive metabolite)

Half-life: 12.9 hr

Excretion: 75% urine; 21% feces

Dosage

Adult

Type 2 Diabetes Mellitus

Initial: 5 mg PO qDay

May increase to 10 mg qDay in patients tolerating 5 mg/day who require additional glycemic control

Pediatric

Safety and efficacy not established

Drug contraindications

Side effects

Interactions

Alerts

Hypotension may occur as a result of intravascular volume contraction, particularly in patients with impaired renal function

Before initiating therapy, assess volume status and correct hypovolemia in the elderly, in patients with renal impairment or low systolic blood pressure, and in patients on diuretics; monitor for signs and symptoms during therapy

Drug increases serum creatinine and decreases eGFR; elderly patients and patients with impaired renal function may be more susceptible to these changes; renal function should be evaluated prior to initiation of therapy and monitored periodically thereafter

Causes intravascular volume contraction and symptomatic hypotension and/or acute kidney injury can occur, particularly if eGFR <60 mL/min/1.73 m²; before initiating therapy, consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure, and concomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs); consider temporarily discontinuing therapy in any setting of reduced oral intake (such as acute illness or fasting) or fluid losses (gastrointestinal illness or excessive heat exposure); monitor for signs and symptoms of acute kidney injury; if acute kidney injury occurs, discontinue therapy promptly and institute treatment;

Bone fractures reported in patients with eGFR 30 to less than 60 mL/min/1.73 m2, for treatment durations up to 104 weeks

Hypoglycemia risk increased with insulin and insulin secretagogues, adjust dose

Genital mycotic infections may occur, patients with history of genital mycotic infections and uncircumcised males are more susceptible

Increases risk of urinary tract infections (UTIs), including life-threatening urosepsis and pyelonephritis that started as UTIs; evaluate for signs and symptoms of urinary tract infections and treat promptly, if indicated

Necrotizing fasciitis of the perineum (Fournier gangrene) reported with SGLT2 inhibitors; signs and symptoms include tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4 F or a general feeling of being unwell; if suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary

Fatal cases of ketoacidosis reported in patients taking dapagliflozin; monitor for symptoms (eg, difficulty breathing, nausea, vomiting, abdominal pain, confusion, unusual fatigue or sleepiness); assess patients who present and consider risk factors for ketoacidosis prior to initiating therapy; patients may require temporary discontinuation of therapy in clinical situation that may predispose to ketoacidosis

Dose-related increases in LDL-C reported

Do not administer to patients with active bladder cancer and use caution in patients with a prior history of bladder cancer

SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests; use alternative methods to monitor glycemic control

Points of recommendation

• Tell all of your health care providers that you take dapagliflozin. This includes your doctors, nurses, pharmacists, and dentists.
• Do not drive if your blood sugar has been low. There is a greater chance of you having a crash.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take dapagliflozin.
• Follow the diet and workout plan that your doctor told you about.
• If you are on a low-salt or salt-free diet, talk with your doctor.
• It may be harder to control your blood sugar during times of stress like when you have a fever, an infection, an injury, or surgery. A change in level of physical activity or exercise and a change in diet may also affect your blood sugar. Talk with your doctor.
• Check your blood sugar as you have been told by your doctor.
• Too much acid in the blood or urine (ketoacidosis) and very bad urinary tract infections (UTIs) have happened with dapagliflozin. Ketoacidosis can be deadly. Both of these health problems may need to be treated in a hospital. Talk with the doctor.
• Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
• If you cannot drink liquids by mouth or if you have upset stomach, throwing up, or diarrhea that does not go away, you need to avoid getting dehydrated. Contact your doctor to find out what to do. Dehydration may lead to new or worse kidney problems.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking dapagliflozin, call your doctor right away.

• Take with or without food.
• Take in the morning.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
• To gain the most benefit, do not miss doses.
• Keep taking dapagliflozin as you have been told by your doctor or other health care provider, even if you feel well.

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

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