Can Irinotecan (Camptosar) cause bradycardia and hypotension?

Can Irinotecan Cause Bradycardia and Hypotension?

Yes, irinotecan can cause both bradycardia and hypotension as part of its cholinergic syndrome, which occurs during or shortly after infusion. These cardiovascular effects are mediated through vagal activation and are reversible with atropine.

Mechanism and Clinical Presentation

Irinotecan causes bradycardia and hypotension through a cholinergic mechanism involving vagal activation, not through acetylcholinesterase inhibition at clinically relevant concentrations. 1

• The cardiovascular effects are abolished by bilateral vagotomy or atropine administration, confirming vagal mediation 1
• These effects occur during or shortly after infusion as part of the acute cholinergic syndrome 2
• The bradycardia and hypotension are transient and respond rapidly to anticholinergic therapy 3, 4

Incidence and Recognition

Cardiovascular toxicity from irinotecan, while documented in the FDA label and case reports, may be underrecognized in clinical practice. 2, 4

• The FDA label documents cardiovascular events including myocardial ischemic events and thromboembolic events in postmarketing surveillance 2
• Cholinergic symptoms (including potential cardiovascular effects) were reported in 47% of patients in clinical trials using the once-every-3-week dosing schedule 2
• Case reports suggest that when specifically monitored, cholinergic cardiovascular effects may be discovered more frequently than previously recognized 4

Clinical Management Algorithm

When bradycardia and hypotension occur during or after irinotecan infusion:

1. Recognize the cholinergic syndrome immediately - symptoms include bradycardia, hypotension, diaphoresis, abdominal cramping, and diarrhea occurring during or within hours of infusion 2, 3

2. Administer atropine 0.5 mg IV as first-line treatment - this rapidly reverses the vagally-mediated cardiovascular effects 1, 3, 4

3. Monitor continuously during subsequent infusions - patients who experience cholinergic symptoms may require prophylactic atropine with future doses 3, 4

4. Do not confuse with late-onset diarrhea - the cholinergic syndrome occurs acutely (during/immediately after infusion), while late diarrhea occurs days later and requires different management 2

Important Clinical Distinctions

The cardiovascular effects of irinotecan differ fundamentally from other causes of chemotherapy-related bradycardia: 5

• Unlike infiltrative causes (lymphoma, amyloidosis) or other chemotherapy agents, irinotecan's effects are acute, transient, and cholinergically mediated 5, 1
• The mechanism does not involve direct cardiac toxicity or conduction system damage 1
• Response to atropine is rapid and complete, unlike bradycardia from other chemotherapy agents that may require pacemaker placement 5

Critical Pitfalls to Avoid

Do not delay atropine administration while pursuing other interventions - the cholinergic mechanism responds specifically and rapidly to anticholinergic therapy 1, 3

Do not discontinue irinotecan based solely on cholinergic cardiovascular effects - these can be managed with prophylactic or therapeutic atropine without dose modification 3, 4

Do not attribute all bradycardia during irinotecan therapy to the drug - consider other causes including concurrent medications (beta-blockers, calcium channel blockers), electrolyte abnormalities, or underlying cardiac disease 5, 6

Monitor more carefully when irinotecan is combined with prochlorperazine - the incidence of akathisia (another cholinergic effect) increases when both drugs are given on the same day 2