What precautions and potential side effects should be considered when prescribing Jardiance (Empagliflozin) or Synjardy (Empagliflozin and Metformin) to patients, especially those with a history of urinary tract infections, genital mycotic infections, or at risk for hypotension?

Precautions and Side Effects for Jardiance (Empagliflozin) and Synjardy (Empagliflozin/Metformin)

Both Jardiance and Synjardy carry significant risks for genital mycotic infections (occurring in 3-5 times more patients than placebo) and require careful patient selection, particularly avoiding use in those with recurrent genital candidiasis, and mandating patient education about genital hygiene and infection symptoms before initiation. 1

Key Contraindications and When NOT to Use

• Severe renal impairment (eGFR <30 mL/min/1.73 m²), end-stage renal disease, or dialysis 2
• History of serious hypersensitivity reaction to empagliflozin 2
• History of recurrent genital candidiasis - this is a relative contraindication requiring careful consideration 1
• Do not initiate if eGFR <45 mL/min/1.73 m² (though can continue if already on therapy and eGFR falls below this level) 1, 2

Critical Safety Warnings Requiring Immediate Action

Volume Depletion and Hypotension Risk

• Before starting, assess volume status in patients with renal impairment, elderly patients, those with low systolic blood pressure, or patients on diuretics 1, 2
• Consider reducing diuretic dose if patient has symptoms of dehydration 1
• Educate patients about dehydration symptoms (lightheadedness, orthostasis, weakness) and instruct them to hold medication if experiencing low oral intake 1

Euglycemic Diabetic Ketoacidosis (DKA)

• Educate patients that DKA can occur even with blood glucose readings in the 150-250 mg/dL range 1
• Instruct patients to seek urgent medical attention if experiencing nausea, vomiting, abdominal pain, or weakness 1
• Discontinue at least 3 days before planned surgery to prevent postoperative ketoacidosis 1, 3
• Hold medication during acute illness, particularly with reduced food/fluid intake, fever, vomiting, or diarrhea 3

Hypoglycemia Management

• If HbA1c is well-controlled at baseline or patient has history of frequent hypoglycemic events, reduce sulfonylurea dose or stop it entirely, and consider reducing total daily insulin dose by ~20% when starting therapy 1

Common Side Effects and Their Management

Genital Mycotic Infections (Most Common)

• Incidence: 3.6-5.7% with empagliflozin vs 1-3.7% with placebo 1, 4, 5
• Women have 4-fold higher risk than men (13.2% vs 3.3%) 4
• Prior history of genital fungal infection increases risk 2.4-fold 4
• Indian populations show particularly high rates (25.9% experiencing at least one episode) 5
• Educate patients regarding genital hygiene importance and daily hygienic measures 1, 3
• Most infections are mild, respond to brief antifungal treatment, and rarely recur 1

Urinary Tract Infections

• Slight increase in UTI risk, though large trials show no significant difference in serious UTIs 1, 6
• Women and patients with SGLT2 inhibitors show higher UTI rates in real-world data 1, 7
• Most infections are mild to moderate and respond to standard antimicrobial treatment 6, 8
• Evaluate and treat promptly if UTI symptoms develop 1, 2
• Rare but serious: urosepsis and pyelonephritis require immediate evaluation 2

Acute Kidney Injury and Renal Function Changes

• Consider temporarily discontinuing in settings of reduced oral intake or fluid losses 2
• Monitor renal function during therapy 2
• If acute kidney injury occurs, discontinue immediately and treat promptly 2
• Use clinical judgment when initiating in patients starting or up-titrating ACE inhibitor or ARB if renal function is impaired 1

Other Notable Side Effects

• Increased LDL cholesterol - monitor and treat as appropriate 1, 2
• Hypersensitivity reactions - discontinue immediately, treat promptly, and monitor until resolution 2
• Rare: necrotizing fasciitis of the perineum (Fournier gangrene) - requires immediate treatment if suspected 3

Special Populations Requiring Extra Caution

Patients with Specific Risk Factors

• History of prior amputation, severe peripheral arterial disease, or active diabetic foot ulcers (note: this caution is primarily for canagliflozin, not empagliflozin) 1
• History of diabetic ketoacidosis 1
• Elderly patients - higher incidence of volume depletion and reduced renal function adverse reactions 2
• Patients considering pregnancy or breastfeeding 1

Women-Specific Considerations

• Urinary tract and genital mycotic infections occur more frequently in women receiving SGLT2 inhibitors 1
• Electrolytes and renal function should be monitored more closely in women 1

Patient Education Checklist Before Starting Therapy

• Genital hygiene importance and infection symptoms 1
• Dehydration symptoms and when to hold medication 1
• DKA symptoms (even with normal glucose readings) 1
• Foot care importance, especially with diabetic neuropathy 1
• Home glucose monitoring for first 4 weeks, especially if on insulin or sulfonylurea 1
• Sick day rules: hold medication during acute illness with reduced oral intake 3