Drug General Information (ID: DDIH5BGI74)
Drug Name			Physostigmine		Drug Info		Crizotinib		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Ophthalmic Glaucoma Agents/Antidotes				Multikinase Inhibitors
Structure

Mechanism of Physostigmine-Crizotinib Interaction (Severity Level: Moderate)
Increased risk of bradycardia Click to Show/Hide Mechanism Graph
Drug Name		Physostigmine				Crizotinib
Mechanism		Bradycardia				Bradycardia
Key Mechanism Factor 1
		Factor Name		Bradycardia
		Factor Description		Bradycardia is a slow heart rate in which the heart beats less than 60 times per minute. If the heart rate is very slow and the heart is not pumping enough oxygen-rich blood to the body, and you may feel dizzy, very tired or weak, and short of breath.
Mechanism Description		Increased risk of bradycardia by the combination of Physostigmine and Crizotinib

Recommended Action
Management		Concomitant use of crizotinib with other agents known to cause bradycardia such as beta-blockers, calcium channel blockers, cholinesterase inhibitors, clonidine, and digoxin should generally be avoided whenever possible. Otherwise, heart rate and blood pressure should be monitored closely. If Grade 2 or 3 symptomatic bradycardia occurs, crizotinib should be withheld, the use of concomitant medications re-evaluated, and the dosage of crizotinib adjusted accordingly. Crizotinib should be permanently discontinued for Grade 4 bradycardia. In patients who develop Grade 4 bradycardia associated with concomitant medications known to cause bradycardia or hypotension, crizotinib should be withheld until Grade 1 or less, and if concomitant medications can be discontinued, crizotinib may be restarted at 250 mg once daily with frequent monitoring.

References
1	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2	Product Information. Xalkori (crizotinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
3	Canadian Pharmacists Association "e-CPS."