JARDIANCE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for JARDIANCE (JARDIANCE).
Sodium-glucose co-transporter 2 (SGLT2) inhibitor; reduces renal glucose reabsorption, lowering blood glucose independent of insulin.
| Metabolism | Primarily metabolized via glucuronidation by UGT1A8, UGT1A9, and UGT2B7; negligible CYP450 involvement. |
| Excretion | Primarily renal: approximately 70-80% of absorbed dose excreted unchanged in urine via glomerular filtration and active tubular secretion. Fecal: ~10-20% via biliary and fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 12.9 hours in healthy subjects. Steady-state is achieved after 4-5 days of once-daily dosing. Effective half-life for accumulation: ~4-6 hours. |
| Protein binding | Approximately 86-90% bound to plasma proteins, predominantly albumin. |
| Volume of Distribution | Volume of distribution at steady state (Vdss) is approximately 0.3-0.4 L/kg (about 20-30 L in a 70 kg individual), suggesting distribution into extracellular fluid. |
| Bioavailability | Oral bioavailability is approximately 78% (range 60-90%) under fasting conditions. Food slightly reduces rate of absorption but not overall extent; thus can be taken with or without food. |
| Onset of Action | Oral administration: Pharmacodynamic effect on urinary glucose excretion begins within 1 hour, with significant effect observed by 2 hours post-dose. |
| Duration of Action | Duration of action: Urinary glucose excretion persists for at least 24 hours, supporting once-daily dosing. Clinical effect on HbA1c reduction seen over 12-24 weeks. |
| Action Class | SGLT2 inhibitors |
| Brand Substitutes | Gibtulio 25mg Tablet, Oboravo 25mg Tablet, Glifaz 25mg Tablet, Cospiaq 25mg Tablet, Gibtulio 10mg Tablet, Oboravo 10mg Tablet, Cospiaq 10mg Tablet |
10 mg orally once daily, may increase to 25 mg orally once daily if tolerated and additional glycemic control needed.
| Dosage form | TABLET |
| Renal impairment | eGFR >= 45 mL/min/1.73 m2: no adjustment; eGFR 30-44 mL/min/1.73 m2: not recommended for glycemic control but may be used for heart failure or CKD if eGFR >= 25; eGFR < 30 mL/min/1.73 m2: contraindicated for glycemic control, may be used for heart failure if eGFR >= 25; eGFR < 25: not recommended. |
| Liver impairment | Mild or moderate hepatic impairment (Child-Pugh A or B): no adjustment; severe hepatic impairment (Child-Pugh C): not recommended. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment based on age alone; however, renal function should be assessed and dose adjusted accordingly per renal adjustment guidelines; monitor for volume depletion and renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for JARDIANCE (JARDIANCE).
| Breastfeeding | Empagliflozin is excreted in rat milk but no data exist in human milk. The M/P ratio is unknown. Due to the potential for adverse effects on the nursing infant, primarily renal development, breastfeeding is not recommended during therapy or for 48 hours after the last dose. |
| Teratogenic Risk | JARDIANCE (empagliflozin) is classified as FDA Pregnancy Category C. In animal studies, empagliflozin caused renal toxicity in offspring at exposures similar to human therapeutic doses. Data in pregnant women are limited; however, due to the mechanism of action (SGLT2 inhibition), there is a potential risk for fetal renal development impairment, particularly in the second and third trimesters. Use during pregnancy is not recommended, especially after 20 weeks gestation, due to risk of fetal renal damage and oligohydramnios. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Severe renal impairment (eGFR <30 mL/min/1.73 m²)","End-stage renal disease or dialysis","History of serious hypersensitivity reaction to any SGLT2 inhibitor","Pregnancy (second and third trimesters) and breastfeeding (limited data)"]
| Precautions | ["Ketoacidosis (including euglycemic ketoacidosis)","Acute kidney injury and impairment in renal function","Volume depletion and hypotension","Urosepsis and pyelonephritis","Lower limb amputation (associated with canagliflozin; risk may apply to class)","Necrotizing fasciitis of the perineum (Fournier gangrene)","Genital mycotic infections and urinary tract infections","Hypoglycemia when used with insulin or insulin secretagogues","Increased LDL-C"] |
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| Fetal Monitoring | If inadvertent exposure occurs during pregnancy, monitor fetal growth and amniotic fluid volume via ultrasound. Assess maternal renal function and blood glucose control. Postnatally, monitor the infant for hypoglycemia and renal function. |
| Fertility Effects | No human studies on fertility have been conducted. In animal studies, no effects on male or female fertility were observed at clinically relevant doses. However, the impact on human fertility is unknown. |