What should be done for a patient experiencing diarrhea, abdominal pain after eating, and chest burning sensation after receiving Mounjaro (tirzepatide) injections?

Management of Mounjaro-Induced Gastrointestinal Symptoms

Stop Mounjaro immediately and initiate symptomatic management with loperamide for diarrhea, proton pump inhibitor for reflux, and ensure adequate hydration while ruling out serious complications like pancreatitis. 1, 2

Immediate Actions Required

Discontinue Tirzepatide

• Permanently discontinue Mounjaro given the severity and duration of gastrointestinal symptoms after 7 injections 1, 2
• Gastrointestinal adverse events are the most common side effects of tirzepatide, occurring in 39-49% of patients in a dose-dependent manner, with nausea and diarrhea being most frequent 1
• Drug discontinuation rates due to adverse events reach 10% at higher doses 1

Rule Out Life-Threatening Complications

• Check serum lipase immediately to exclude acute pancreatitis, which is a documented but rare complication of tirzepatide 3, 1
• Obtain comprehensive metabolic panel including electrolytes (potassium, magnesium, calcium) as severe GI symptoms can cause profound electrolyte disturbances leading to life-threatening arrhythmias 2
• The case of ventricular fibrillation from tirzepatide-induced electrolyte derangement (K⁺ 2.2, Mg²⁺ 1.1) demonstrates this is not merely theoretical 2
• If epigastric pain worsens or lipase is elevated >3x upper limit of normal, obtain CT abdomen to evaluate for pancreatitis 3

Assess for Infectious Causes

• Send stool for C. difficile testing given the diarrhea and recent medication use 4
• While awaiting results, it is generally safe to start symptomatic treatment, but reassess regularly 4

Symptomatic Management

Diarrhea Control

• Start loperamide 4 mg initially, then 2 mg after each loose stool (maximum 16 mg/day) 4
• Loperamide is effective for diarrhea but titrate carefully to avoid constipation, bloating, and nausea 4
• Do not use loperamide if C. difficile is confirmed or if there are signs of colitis (bloody stools, severe abdominal pain, fever) as it may precipitate toxic megacolon 4

Reflux Management

• Initiate proton pump inhibitor (e.g., omeprazole 20-40 mg daily) for the chest burning sensation 1
• The "chest burning" likely represents gastroesophageal reflux, a common GI manifestation of GLP-1 agonists 1

Abdominal Pain

• Avoid NSAIDs as they can worsen GI symptoms and increase risk of complications 4
• Consider hyoscine butylbromide 10-20 mg three times daily for cramping abdominal pain if needed 4

Hydration and Electrolyte Replacement

• Aggressive oral rehydration with electrolyte-containing solutions 2
• If unable to tolerate oral intake or signs of dehydration (dark urine, dizziness, reduced performance status), admit for IV fluid resuscitation 4
• Recheck electrolytes within 24-48 hours given the risk of severe depletion from ongoing diarrhea 2

Monitoring and Follow-Up

Short-Term (24-48 hours)

• Monitor for worsening symptoms including increased abdominal pain, fever, bloody stools, or signs of dehydration 4
• If symptoms do not improve within 48-72 hours after stopping tirzepatide, consider further evaluation including colonoscopy to exclude drug-induced colitis 4

Medium-Term (1-2 weeks)

• GI symptoms from tirzepatide typically resolve within days to weeks after discontinuation 1
• If diarrhea persists beyond 2 weeks, investigate for other causes including bile acid malabsorption, small intestinal bacterial overgrowth, or lactose intolerance 4

Long-Term Glycemic Management

• Do not restart tirzepatide given the severity of adverse events 1
• Consider alternative diabetes management strategies that avoid GLP-1/GIP agonists 3
• If incretin-based therapy is still desired, switching between GLP-1 agonists may increase risk of adverse effects and should be approached with extreme caution 3

Critical Pitfalls to Avoid

• Never dismiss severe GI symptoms as "expected side effects" - they can herald life-threatening complications like pancreatitis or severe electrolyte disturbances 3, 2
• Do not continue tirzepatide hoping symptoms will resolve - the dose-dependent nature means symptoms often worsen with continued use 1
• Avoid antimotility agents if infectious colitis is suspected until C. difficile and other pathogens are excluded 4
• Do not overlook electrolyte monitoring - the combination of vomiting and diarrhea can rapidly lead to dangerous hypokalemia, hypomagnesemia, and hypocalcemia 2