What is the management for an overdose of tirzepatide (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist)?

Management of Tirzepatide Overdose

In the event of a tirzepatide overdose, contact Poison Control for the latest recommendations and initiate appropriate supportive treatment based on the patient's clinical signs and symptoms, with a monitoring period that accounts for tirzepatide's long half-life of approximately 5 days. 1

Initial Assessment and Management

• For patients with suspected tirzepatide overdose, immediate contact with Poison Control is essential to obtain the most current management recommendations 1
• Supportive care should be the primary approach, as there is no specific antidote for tirzepatide overdose 1
• Monitor vital signs, blood glucose levels, and hydration status, as tirzepatide affects glucose metabolism and can cause gastrointestinal symptoms that may lead to dehydration 2

Monitoring Parameters

• Blood glucose monitoring should be performed frequently, as tirzepatide enhances insulin secretion and reduces glucagon levels in a glucose-dependent manner, which could potentially lead to hypoglycemia in overdose situations 1
• Assess for signs of severe gastrointestinal adverse effects, which are the most common adverse events with tirzepatide (39-49% depending on dose) 2
• Monitor for at least 24 hours, but be aware that the elimination half-life of tirzepatide is approximately 5 days, requiring extended observation in severe cases 1

Management of Specific Complications

Hypoglycemia Management

• Administer oral carbohydrates if the patient is conscious and able to swallow safely 3
• For severe hypoglycemia or in patients unable to take oral carbohydrates, administer intravenous glucose or glucagon 3
• The risk of hypoglycemia with tirzepatide is dose-dependent, with rates of mild hypoglycemia (blood glucose <70 mg/dL) reported as high as 22.6% with the 10 mg dose 2

Gastrointestinal Symptoms

• Provide antiemetics for nausea and vomiting, which are the most common adverse effects of tirzepatide 2
• Ensure adequate hydration, potentially with intravenous fluids if oral intake is compromised due to persistent vomiting 2
• Monitor renal function in patients experiencing severe gastrointestinal reactions, especially those with pre-existing renal impairment 1

Rare but Serious Complications

• Monitor for signs of ketoacidosis, which has been reported with tirzepatide use, even in non-diabetic patients 4
• Check serum and urine ketone levels if ketoacidosis is suspected, particularly in patients with significant anorexia or reduced food intake 4
• Be vigilant for signs of acute pancreatitis, cholelithiasis, or cholecystitis, although these complications are rare (≤1%) with tirzepatide 2

Special Considerations

• For patients with renal impairment, no specific dosage adjustment is needed during management of overdose, as renal impairment does not significantly impact tirzepatide pharmacokinetics 1
• Similarly, hepatic impairment does not affect tirzepatide pharmacokinetics, so no specific adjustments are needed for these patients 1
• Be aware that tirzepatide delays gastric emptying, which may affect the absorption of concomitantly administered oral medications used in management 1

Follow-up and Prevention

• After the acute management phase, evaluate the circumstances of the overdose to prevent recurrence 5
• Consider medication reconciliation and patient education about proper dosing and administration 5
• For patients on tirzepatide who experienced an overdose, reassess the appropriateness of continuing therapy and potentially adjust the dose if therapy is to be continued 5