Can Mounjaro (tirzepatide) cause hypotension?

Hypotension Associated with Tirzepatide (Mounjaro)

Yes, tirzepatide (Mounjaro) can cause hypotension as an adverse effect, particularly in patients with cardiovascular conditions or those taking other medications that lower blood pressure.

Mechanism and Evidence

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist approved for type 2 diabetes management 1. Recent evidence from a retrospective observational study on adverse drug reactions (ADRs) to tirzepatide identified hypotension among the reported cardiovascular effects 1.

The hypotensive effect appears to be:

• Most common within the first 1-6 months of treatment
• Dose-dependent, with cases reported across all dosages but most frequently at 2.5-5 mg
• Classified as "probable" in causality assessment using the Naranjo scale 1

Risk Factors for Tirzepatide-Induced Hypotension

Several factors may increase the risk of hypotension with tirzepatide:

1. Concurrent antihypertensive medications: Beta-blockers, calcium channel blockers, and ACE inhibitors can have additive hypotensive effects 2

2. Pre-existing cardiovascular conditions: Patients with cardiovascular disease require more intensive monitoring 1

3. Volume depletion: Patients who are volume depleted (e.g., from diuretic therapy) may be more susceptible 2

4. Rapid weight loss: Significant weight reduction with tirzepatide may contribute to hypotension 1

Management Recommendations

For patients experiencing hypotension on tirzepatide:

Immediate Management

• Assess for symptoms of hypoperfusion (dizziness, lightheadedness, blurred vision)
• If hypotension is accompanied by clinical evidence of hypoperfusion, consider dose reduction or discontinuation of tirzepatide 1
• Administer the medication and any concurrent antihypertensive drugs at different times of day to minimize risk 2

Preventive Measures

• Monitor blood pressure regularly, especially during the first 6 months of treatment
• Consider temporary reduction in the dose of concurrent antihypertensive medications, particularly diuretics in volume-depleted patients 2
• Ensure adequate hydration and salt intake
• Start with the lowest dose of tirzepatide (2.5 mg) and titrate slowly based on tolerance 3

Special Populations

• Elderly patients: Use with particular caution due to increased risk of hypotension 3
• Patients with cardiovascular disease: Implement more intensive monitoring of cardiovascular parameters 1
• Patients on multiple antihypertensive medications: Consider medication review and possible adjustment of other agents

Clinical Pearls and Pitfalls

• Hypotension with tirzepatide may be asymptomatic in some patients but can cause significant symptoms in others
• The hypotensive effect may be more pronounced during the initial titration period
• Patients experiencing rapid weight loss on tirzepatide may require adjustment of their antihypertensive regimen
• Concomitant use with other medications that can cause hypotension (e.g., opioids, certain antidepressants) may increase risk 2
• Unlike some beta-blockers that can cause rebound hypertension upon discontinuation, there's no evidence suggesting abrupt discontinuation of tirzepatide causes similar effects

In conclusion, clinicians should be vigilant about the potential for hypotension when prescribing tirzepatide, especially in patients with cardiovascular comorbidities or those on multiple antihypertensive medications. Regular blood pressure monitoring and appropriate dose adjustments of concurrent medications are essential to minimize this risk.