Drug Interactions between Synalgos-DC and varenicline

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.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.