What to do about clear vomit and abdominal pain after starting apixaban (anticoagulant) and dapagliflozin (SGLT2 inhibitor)?

Immediate Evaluation for Euglycemic Diabetic Ketoacidosis

Stop dapagliflozin immediately and check serum or urine ketones urgently, as clear vomit and abdominal pain after starting this SGLT2 inhibitor are classic warning signs of euglycemic diabetic ketoacidosis (DKA), a potentially life-threatening complication that can occur even with normal blood glucose levels. 1

Critical First Steps

• Discontinue dapagliflozin now and do not restart until the patient has fully recovered from this acute illness 2
• Check blood glucose, serum ketones (beta-hydroxybutyrate preferred), venous blood gas for anion gap acidosis, and basic metabolic panel 1, 3
• Assess volume status carefully, as the combination of vomiting and dapagliflozin's diuretic effect significantly increases hypovolemia risk 1, 2
• If ketones are elevated or anion gap acidosis is present, initiate DKA protocol with IV fluids and insulin even if glucose is normal 1, 3

Why This Presentation is High-Risk

• Patients on SGLT2 inhibitors should seek immediate care when developing nausea, vomiting, abdominal pain, or generalized weakness, as these are potential symptoms of euglycemic DKA 1
• The risk of euglycemic DKA is very low in large trials but becomes clinically significant during acute illness with reduced food/fluid intake 1, 2
• A 53-year-old patient on dapagliflozin presented with identical symptoms (nausea, vomiting, abdominal pain) and was diagnosed with euglycemic DKA despite blood glucose of only 162 mg/dL 3

Differential Diagnosis to Consider

Acute pancreatitis must be ruled out, as dapagliflozin has been associated with this condition in case reports 4:

• Check serum lipase and amylase levels
• Consider abdominal imaging if lipase is elevated or clinical suspicion is high
• A 58-year-old male with no risk factors developed acute pancreatitis shortly after starting dapagliflozin, which resolved after discontinuation 4

Apixaban-related bleeding should be evaluated given the "hard stomach" complaint 5:

• Check complete blood count for anemia
• Assess for signs of intra-abdominal bleeding (hypotension, tachycardia, peritoneal signs)
• While rare, spontaneous splenic rupture has occurred with apixaban, presenting as severe abdominal pain 5
• Consider holding apixaban temporarily if significant bleeding is suspected, though this requires careful risk-benefit assessment 1

Sick Day Protocol Implementation

• Patients must be counseled to stop dapagliflozin immediately during any acute illness, particularly with reduced food/fluid intake, fever, vomiting, or diarrhea 2
• Maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held, as complete insulin cessation increases DKA risk 1, 2
• Resume dapagliflozin only after the patient has recovered from acute illness and normal oral intake is re-established 2

Volume Status Management

• The diuretic effect of dapagliflozin combined with illness-related fluid losses (vomiting) significantly increases hypovolemia risk 1, 2
• Elderly patients and those on concurrent diuretic therapy are at higher risk of volume depletion 1, 2
• Provide IV fluid resuscitation if signs of volume depletion are present (orthostatic hypotension, tachycardia, decreased urine output) 1

When to Seek Emergency Care

This patient requires immediate emergency department evaluation if any of the following are present 1, 3:

• Persistent vomiting preventing oral intake
• Signs of severe dehydration or shock
• Altered mental status or severe weakness
• Respiratory distress (Kussmaul breathing suggesting metabolic acidosis)
• Severe or worsening abdominal pain

Long-Term Management Considerations

• Once acute illness resolves, reassess whether dapagliflozin should be restarted or an alternative agent chosen 2
• If euglycemic DKA is confirmed, consider permanent discontinuation of dapagliflozin and use alternative glucose-lowering or cardioprotective agents 1
• Provide written sick day management instructions emphasizing immediate discontinuation during illness 2
• Apixaban can generally be continued for atrial fibrillation unless bleeding complications occur, though perioperative management may require temporary interruption 1