Drug Interactions between Metoprolol Succinate ER and varenicline

ADJUST DOSING INTERVAL: The bioavailability of metoprolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take metoprolol at the same time each day, preferably with or immediately following meals.

GENERALLY AVOID: Varenicline may enhance the effects of alcohol as well as alter the way an individual reacts to alcohol. During postmarketing use, some patients have reported experiencing increased intoxicating effects of alcohol while taking varenicline. In addition, some reported cases of neuropsychiatric events, including unusual and sometimes aggressive behavior directed toward oneself or others, may have been worsened by concomitant use of alcohol. These events were often accompanied by amnesia.

MANAGEMENT: Patients should be advised to limit their consumption of alcohol until they know whether varenicline affects their tolerance for alcohol, and to exercise caution driving or operating machinery until they know how quitting smoking and/or varenicline may affect them. Patients should immediately stop taking varenicline and contact their physician if they develop agitation, hostility, aggressive behavior, depressed mood, or changes in behavior or thinking that are not typical for them, or if they develop suicidal ideation or behavior.

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.