Empagliflozin

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

You may take empagliflozin with or without food, but take it the same way each time.

Your blood sugar will need to be checked often, and you may need other medical tests at your doctor's office.

You may have very low blood pressure while taking this medication. Call your doctor if you are sick with vomiting or diarrhea, or if you are sweating more than usual.

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, pale skin, irritability, dizziness, feeling shaky, or trouble concentrating. Always keep a source of sugar with you in case you have low blood sugar. Sugar sources include fruit juice, hard candy, crackers, raisins, and non-diet soda. Be sure your family and close friends know how to help you in an emergency.

If you have severe hypoglycemia and cannot eat or drink, use a glucagon injection. Your doctor can prescribe a glucagon emergency injection kit and tell you how to use it.

Also watch for signs of high blood sugar (hyperglycemia) such as increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, and weight loss.

Check your blood sugar carefully during times of stress, travel, illness, surgery or medical emergency, vigorous exercise, or if you drink alcohol or skip meals. These things can affect your glucose levels and your dose needs may also change. Do not change your medication dose or schedule without your doctor's advice.

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 empagliflozin.

Empagliflozin is only part of a treatment program that may also include diet, exercise, weight control, blood sugar testing, and special medical care. Follow your doctor's instructions very closely.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

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.

Mechanism of Action

Selective sodium-glucose transporter-2 (SGLT2) inhibitor

SGLT2 is expressed in the proximal renal tubules and is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen; SGLT2 inhibitors reduce glucose reabsorption and lower the renal threshold for glucose, thereby increasing urinary glucose excretion

Absorption

Peak plasma time: 1.5 hr

Peak plasma concentration: 259 nmol/L (10 mg/day); 687 nmol/L (25 mg/day)

AUC: 1870 nmol•h/L (10 mg/day); 4740 nmol•h/L (25 mg/day)

Distribution

Protein bound: 86.2%

Red blood cell partitioning: 36.8%

Vd: 73.8 L

Metabolism

Primary route of metabolism is glucuronidation by the uridine 5'-diphospho-glucuronosyltransferases UGT2B7, UGT1A3, UGT1A8, and UGT1A9

No major metabolites were detected and the most abundant metabolites were 3 glucuronide conjugates (2-O-, 3-O-, and 6-O-glucuronide)

Systemic exposure of each metabolite was <10%

Elimination

Half-life: 12.4 hr

Clearance: 10.6 L/hr

Excretion: 54.4% urine; 41.2% feces

Empagliflozin is part of the drug class:

• Other blood glucose lowering drugs, excl. insulins

Before taking empagliflozin, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to empagliflozin or to any of its ingredients
• have kidney problems
• are pregnant or breastfeeding

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

Empagliflozin may be found in some form under the following brand names:

• Jardiance

Empagliflozin is part of the drug class:

• Other blood glucose lowering drugs, excl. insulins

Serious side effects have been reported with empagliflozin. See the “empagliflozin Precautions” section.

A common side effect of empagliflozin is urinary tract infections.

This is not a complete list of empagliflozin side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Store empagliflozin tablets at room temperature.
• Keep this and all medicines out of the reach of children.

You should not use empagliflozin if you have severe kidney disease or if you are on dialysis, or if you have diabetic ketoacidosis. Empagliflozin is not for treating type 1 diabetes.

Taking empagliflozin can make you dehydrated, which could cause you to feel weak or dizzy (especially when you stand up).

Empagliflozin can also cause infections in the bladder or genitals (penis or vagina). Call your doctor if you have genital pain or itching, genital odor or discharge, increased urination, pain or burning when you urinate, or blood in your urine.

Usual Adult Dose for Diabetes Type 2:

Initial dose: 10 mg orally once a day in the morning
-May increase to 25 mg orally once a day for patients tolerating therapy
Maximum dose: 25 mg per day

Comments:
-Limitation of use: Not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
-Volume depletion should be corrected prior to initiating therapy.

Uses:
-An adjunct to diet and exercise to improve glycemic control in adults with Type 2 diabetes mellitus.
-To reduce the risk of cardiovascular (CV) death in adult patients with type 2 diabetes mellitus and established CV disease.

Usual Adult Dose for Cardiovascular Risk Reduction:

Initial dose: 10 mg orally once a day in the morning
-May increase to 25 mg orally once a day for patients tolerating therapy
Maximum dose: 25 mg per day

Comments:
-Limitation of use: Not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
-Volume depletion should be corrected prior to initiating therapy.

Uses:
-An adjunct to diet and exercise to improve glycemic control in adults with Type 2 diabetes mellitus.
-To reduce the risk of cardiovascular (CV) death in adult patients with type 2 diabetes mellitus and established CV disease.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In the U.S.

• Jardiance

Available Dosage Forms:

• Tablet

Therapeutic Class: Antidiabetic

Pharmacologic Class: Sodium Glucose Co-Transporter 2 Inhibitor

• It is used to lower blood sugar in patients with high blood sugar (diabetes).
• It is used to lower the chance of death from heart disease in certain people.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Jardiance: 10 mg, 25 mg

By inhibiting sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules, empagliflozin 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.

Distribution

Vd: 73.8 L

Metabolism

Primarily through glucuronidation by UGT2B7, UGT1A3, UGT1A8, and UGT1A9 to minor metabolites

Excretion

Urine (54.4%; 50% as unchanged drug); feces (41.2%; majority as unchanged drug)

Time to Peak

1.5 hours

Half-Life Elimination

12.4 hours

Protein Binding

86.2%

History of serious hypersensitivity to empagliflozin or any component of the formulation; severe renal impairment (eGFR <30 mL/minute/1.73 m2), end-stage renal disease (ESRD), or dialysis

Canadian labeling: Additional contraindications (not in US labeling): eGFR <45 mL/minute/1.73 m2

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Insulin: SGLT2 Inhibitors may enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Loop Diuretics: Empagliflozin may enhance the hypotensive effect of Loop Diuretics. Monitor therapy

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Sulfonylureas: SGLT2 Inhibitors may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Teriflunomide: May increase the serum concentration of OAT3 Substrates. Monitor therapy

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Applies to empagliflozin: oral tablet

Cardiovascular

Volume depletion included decreased ambulatory blood pressure, decreased systolic blood pressure, dehydration, hypotension, hypovolemia, orthostatic hypotension, and syncope.[Ref]

Uncommon (0.1% to 1%): Volume depletion[Ref]

Renal

Common (1% to 10%): Increased urination
Uncommon (0.1% to 1%): Dysuria
Frequency not reported: Increased serum creatinine, decreased eGFR
Postmarketing reports: Acute kidney injury, urosepsis, pyelonephritis[Ref]

Genitourinary

Common (1% to 10%): Female and male genital mycotic infections, urinary tract infection
Uncommon (0.1% to 1%): Phimosis[Ref]

Metabolic

Frequency of hypoglycemia depended on the type of background therapy used. In combination with metformin and sulfonylurea, hypoglycemia was reported in 16.1% of patients taking the 10 mg dose and 11.5% in patients taking the 25 mg dose. In combination with insulin, hypoglycemia was reported in 22.5% of patients taking the 10 mg dose and 29.7% in patients taking the 25 mg dose.

Twenty reports of acidosis have been identified in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database during the period March 2013 through 06 June 2014. All patients required emergency room treatment or hospitalization. These cases were not typical of ketoacidosis or diabetic ketoacidosis (DKA) in that they occurred in patients with type 2 diabetes and their blood sugar levels were only slightly increased. Some factors identified as potentially triggering the acidosis included major illness, reduced food and fluid intake, and reduced insulin dose.[Ref]

Common (1% to 10%): Increased low-density lipoprotein cholesterol
Frequency not reported: Hypoglycemia
Postmarketing reports: Acidosis including diabetic ketoacidosis, ketoacidosis, or ketosis[Ref]

General

The most common reported side effects included urinary tract infections and female genital mycotic infections.[Ref]

Dermatologic

Common (1% to 10%): Pruritus[Ref]

Gastrointestinal

Common (1% to 10%): Nausea[Ref]

Hematologic

Common (1% to 10%): Increased hematocrit[Ref]

Musculoskeletal

Common (1% to 10%): Arthralgia[Ref]

Other

Common (1% to 10%): Polydipsia[Ref]

Respiratory

Common (1% to 10%): Upper respiratory tract infection[Ref]

Some side effects of empagliflozin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.