Dapagliflozin

• The recommended starting dose of dapagliflozin is 5 mg by mouth once daily in the morning.
• Dapagliflozin may be taken with or without food.
• The dose may be increased to 10 mg once daily in patients who require additional glycemic control. Kidney function must be assessed before starting treatment.
• Dapagliflozin should not be used in patient whose estimated glomerular filtration rate (eGFR) is <60 ml/min/1.73m2.

Contraindications

Documented hypersensitivity

Severe renal impairment (eGFR <30 mL/min/1.73 m²), end-stage renal disease, or patients on dialysis

Cautions

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

Consider temporarily discontinuing in settings of reduced oral intake or fluid losses; if acute kidney injury occurs, discontinue and promptly treat; monitor renal function during therapy

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 patients for signs and symptoms of acute kidney injury; if acute kidney injury occurs, discontinue therapy promptly and institute treatment;

Not recommended in patients with an eGFR persistently between 30 and less than 60 mL/min/1.73 m² contraindicated if eGFR <30 mL/min/1.73 m²

Monitor renal function prior to initiating therapy and monitored periodically thereafter

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

Ketoacidosis associated with SGLT2 inhibitors reported; monitor for signs of ketoacidosis, even if blood glucose levels are <250 mg/dL, and advise patients to seek immediate medical attention for symptoms (eg, difficulty breathing, nausea, vomiting, abdominal pain, confusion, unusual fatigue or sleepiness); 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

Across 22 clinical studies, newly diagnosed cases of bladder cancer were reported in 10/6045 patients (0.17%) treated with dapagliflozin and 1/3512 patient (0.03%) treated with placebo/comparator; bladder cancer risk factors and hematuria (a potential indicator of preexisting tumors) were balanced between treatment arms at baseline and there were too few cases to determine whether the emergence of these events is related to dapagliflozin

Therapy should not be administered to patients with active bladder cancer and should be administered with caution in patients with a prior history of bladder cancer

No conclusive evidence of macrovascular risk reduction with dapagliflozin or any other antidiabetic agent

GLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests; use alternative methods to monitor glycemic control

Dapagliflozin is a prescription medication used to control blood sugar levels in people with type 2 diabetes. Dapagliflozin is part of a new class of drugs that work in the kidney to block a protein called SGLT2. By blocking this protein, the drug can remove excess glucose (sugar) and calories in the urine, which then helps lower blood sugar levels.

This medication comes in tablet form and is usually taken once daily. Dapagliflozin tablets should be swallowed whole and can be taken with or without food.

Common side effects of dapagliflozin include low blood sugar (hypoglycemia), yeast infections of the penis or vagina, and back ache.

• have type 1 diabetes
• have increased levels of “ketone bodies” in your urine or blood, seen in tests
• have a kidney problem 
• have a liver problem
• have a history of serious heart disease or if you have had a stroke
• are are on medicines to lower your blood pressure (anti-hypertensives) and have a history of low blood pressure (hypotension) 
• have very high levels of glucose in your blood which may make you dehydrated
• have or develop nausea (feeling sick), vomiting or fever or if you are not able to eat or drink. These conditions can cause dehydration.
• often get infections of the urinary tract
• are 75 years old or older
• are taking another medicine for diabetes that contains “pioglitazone”
• have an increase in the amount of red blood cells in your blood, seen in tests
• are pregnant or breastfeeding

Tell your doctor about all of the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements.

Dapagliflozin is usually taken once per day in the morning. Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take dapagliflozin with or without food.

Call your doctor if you are sick with vomiting or diarrhea, if you consume less food or fluid than usual, or if you are sweating more than usual.

Your blood sugar will need to be checked often, and you may also need to test the level of ketones your urine. Dapagliflozin can cause life-threatening ketoacidosis (too much acid in the blood). Even if your blood sugar is normal, contact your doctor if a urine test shows that you have ketones in the urine.

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.

This medicine can cause positive results with certain lab tests for glucose (sugar) in the urine. Tell any doctor who treats you that you are using dapagliflozin.

Dapagliflozin is only part of a 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.

Store at room temperature away from moisture and heat.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• little or no urination;

• ketoacidosis (too much acid in the blood)--nausea, vomiting, stomach pain, confusion, unusual drowsiness, or trouble breathing;

• dehydration symptoms--dizziness, weakness, feeling light-headed (like you might pass out);

• signs of a bladder infection--pain or burning when you urinate, increased urination, blood in your urine, fever, pain in your pelvis or back; or

• signs of a genital infection (penis or vagina)--pain, burning, itching, rash, redness, odor, or discharge.

Some people taking this medicine have had bladder cancer, but it is not clear if dapagliflozin was the actual cause.

Side effects may be more likely to occur in older adults.

Common side effects may include:

• urinating more than usual; or

• sore throat and runny or stuffy nose.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Dapagliflozin is used to treat type 2 diabetes. It works in the kidneys to prevent absorption of glucose (blood sugar). This helps lower the blood sugar level. Dapagliflozin does not help patients who have insulin-dependent or type 1 diabetes. Type 1 diabetic patients must use insulin injections.

dapagliflozin is available only with your doctor's prescription.

Take dapagliflozin only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. Do not change your dose unless directed by your doctor.

dapagliflozin should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Carefully follow the special meal plan your doctor gave you. This is the most important part of controlling your diabetes, and will help the medicine work properly. Exercise regularly and test for sugar in your blood or urine as directed.

Tell your doctor if you are on a low-salt diet.

You may take dapagliflozin with or without food.

Dosing

The dose of dapagliflozin will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of dapagliflozin. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For type 2 diabetes:
    • Adults—At first, 5 milligrams (mg) once a day, taken in the morning. Your doctor may adjust your dose as needed and tolerated.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of dapagliflozin, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• If you have an allergy to dapagliflozin or any other part of dapagliflozin.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Acidic blood problem, bladder cancer, or type 1 diabetes.
• If you have kidney disease.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take dapagliflozin with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

(dap a gli FLOE zin)

By inhibiting sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules, dapagliflozin reduces reabsorption of filtered glucose from the tubular lumen and lowers the renal threshold for glucose (RTG). SGLT2 is the main site of filtered glucose reabsorption; reduction of filtered glucose reabsorption and lowering of RTG result in increased urinary excretion of glucose, thereby reducing plasma glucose concentrations.

Metabolism

Primarily mediated by UGT1A9 to an inactive metabolite (dapagliflozin 3-O-glucuronide); CYP-mediated metabolism (minor)

Excretion

Urine (75%; < 2% as parent drug); feces (21%; ~15% as parent drug)

Time to Peak

2 hours

Half-Life Elimination

~12.9 hours

Protein Binding

91%

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

More frequently reported side effects include: cystitis, pyelonephritis, urinary tract infection, vulvovaginal candidiasis, bacterial vaginosis, genital candidiasis, genitourinary infection, prostatitis, urethritis, vaginal infection, vulvitis, and vulvovaginitis. See below for a comprehensive list of adverse effects.

Initial dose: 5 mg orally once a day
Maximum dose: May increase to 10 mg orally once a day in patients tolerating therapy with 5 mg/day and requiring additional glycemic control

Comments:
-If used in combination with insulin or an insulin secretagogue, a lower dose of insulin or the insulin secretagogue should be considered to reduce the risk of hypoglycemia.

Use: As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.