Dosing and uses of Empagliflozin
Adult dosage forms and strengths
tablet
- 10mg
- 25mg
Type 2 Diabetes Mellitus
Indicated as an addition to diet and exercise to improve glycemic control in adults with type 2 diabetes
10 mg PO qDay in the morning, taken with or without food
May increase to 25 mg/day if needed and tolerated
Dosage modifications
Hepatic impairment: No dosage adjustment required
Renal Impairment
- eGFR <45 mL/min/1.73 m²: Do not initiatee
- GFR ≥45 mL/min/1.73 m²: No dosage adjustment required
- Discontinue if eGFR persistently falls below 45 mL/min/1.73 m²
Dosing Considerations
Not indicated for treatment of type 1 diabetes or diabetic ketoacidosis
Assess renal function before initiating and periodically thereafter
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Geriatric dosage forms and strengths
No dosage change is recommended based on age; see Adult Dosing
Risk of volume depletion-related adverse reactions increased in patients who were ≥75 yr to 2.1%, 2.3%, and 4.4% for placebo, 10 mg, and 25 mg, respectively
Risk of urinary tract infections increased in patients who were ≥75 yr to 10.5%, 15.7%, and 15.1% in patients randomized to placebo, 10 mg, and 25 mg, respectively
Empagliflozin adverse (side) effects
1-10%
Urinary tract infection (7.6-9.3%)
Female genital mycotic infections (5.4-6.4%)
Upper respiratory tract infection (3.1-4%)
Increased urination (3.2-3.4%)
Dyslipidemia (2.3-2.4%)
Male genital mycotic infections (1.6-3.1%)
Nausea (1.1-2.3%)
Polydipsia (1.5-1.7%)
Postmarketing reports
Severe and disabling arthralgia
Warnings
Contraindications
Hypersensitivity
Severe renal impairment, end-stage renal disease, or dialysis
Cautions
Causes intravascular volume contraction; symptomatic hypotension may occur after initiating, particularly in patients with renal impairment, low systolic blood pressure, on diuretics, or in the elderly
Correct volume status before initiating if needed and monitor renal function periodically thereafter
Increases serum creatinine and decreases eGFR; risk increased in elderly or those with moderate renal impairment
Hypoglycemia risk increased with insulin and insulin secretagogues (eg, sulfonylureas); a lower dose of insulin or the insulin secretagogue may be required
Genital mycotic infections may occur; patients with history of genital mycotic infections and uncircumcised males are more susceptible
Dose-related increases in LDL-C reported
GLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests; use alternative methods to monitor glycemic controL
Monitoring glycemic control with 1,5-AG assay is not recommended; this test is unreliable in assessing glycemic control in patients taking SGLT2 inhibitors
Increases risk of urinary tract infections (UTIs), including life-threatening urospesis and pyelonephritis that started as UTIs
Fatal cases of ketoacidosis associated with SGLT2 inhibitors reported; monitor for signs of ketoacidosis and advise patients to seek immediate medical attention for symptoms (eg, difficulty breathing, nausea, vomiting, abdominal pain, confusion, unusual fatigue or sleepiness); assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level; consider risk factors for ketoacidosis prior to initiating therapy; patients may require temporary discontinuation of therapy in clinical situation that may predispose to ketoacidosis
No conclusive evidence of macrovascular risk reduction with empagliflozin or any other antidiabetic agent
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if distributed in human breast milk; secreted in the milk of lactating rats, reaching levels up to 5 times higher than that in maternal plasma
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Empagliflozin
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
Administration
Oral Administration
May take with or without food
Advise patient to have adequate fluid intake to decreased risk of hypotension
