An 82 y/o PACE participant was discharged from the local hospital with 3 new psychiatric prescriptions:
- Citalopram 20mg QAM
- Valproic acid 500mg BID
- Quetiapine 25mg QHS
His relevant PMH is significant for hypertensive heart disease, atrial fibrillation, and acid reflux for which he is being treated with:
- Digoxin 125mcg QD for atrial fibrillation
- Doxazosin 4mg QD for hypertension
- Furosemide 80mg QD for hypertension
- Losartan 50mg QD for hypertension
- Metoprolol XL 50mg QAM for hypertension
- Potassium chloride 20mEq QAM for potassium supplementation (due to furosemide)
- Omeprazole 20mg QAM for acid reflux
Given this participant’s PMH and concomitant medications, the clinical pharmacist was concerned that this new prescription for citalopram might put him at risk for QT prolongation and potentially fatal cardiac arrhythmias. This participant was discharged on the maximum geriatric recommended dose of citalopram: 20mg.
Recent epidemiological studies have shown that doses higher than 20mg in patients >60 years of age increase the risk for QT prolongation. While the citalopram was prescribed at the 20mg dose, the pharmacist realized this participant would end up with higher plasma concentrations than anticipated from a typical 20mg dose due to “kinetic boosting” via competitive inhibition.
Omeprazole is a “moderate” CYP2C19 inhibitor. Citalopram is metabolized extensively by CYP2C19. A 2010 pharmacokinetic study showed that after 18 days of concurrent treatment with citalopram and omeprazole 20mg, the citalopram plasma concentrations were approximately 120% higher versus treatment without concurrent omeprazole.1 Therefore, this participant could potentially end up with higher citalopram plasma levels than typically expected from 20mg. Specifically, citalopram plasma concentrations could be equivalent to >40mg—more than double the current geriatric dosing recommendations!
Furthermore, the participant’s genetic make-up was unknown: if he were a CYP2C19 “poor metabolizer,” the plasma concentrations of citalopram would be even higher still.
The risk for QT prolongation is further increased, given this participant’s cardiac history, use of furosemide (associated with electrolyte disturbances), and quetiapine (associated with QT prolongation), and use of digoxin and metoprolol (both may slow heart rate and precipitate bradycardia, which has been associated with QT prolongation).
The clinical pharmacist alerted the doctor of the citalopram-omeprazole interaction and recommended switching the proton-pump inhibitor (PPI) to pantoprazole, since it was not clinically appropriate to discontinue PPI therapy at the time. Pantoprazole does not inhibit CYP2C19 to the extent that omeprazole does, and will not “boost” the plasma concentrations of citalopram.
1. Rocha A, Coelho EB, Sampaio SA, et al, “Omeprazole Preferentially Inhibits the Metabolism of (+)-(S)-Citalopram in Healthy Volunteers,” Br J Clin Pharmacol, 2010, 70(1):43-51