Drug Interaction Report

Pralidoxime and other drugs within the family of compounds called oximes, such as obidoxime, may potentiate the pharmacologic effects of atropine. Signs of atropinization such as flushing, mydriasis, tachycardia, and dry mouth and nose may occur earlier than expected during coadministration with pralidoxime relative to administration of atropine alone, particularly if the total dose of atropine has been large and the administration of pralidoxime was delayed. Clinicians should be aware of the potential interaction and monitor patients as appropriate. Pralidoxime may be used in conjunction with atropine in the treatment of organophosphate insecticide poisoning and nerve agent poisoning in terrorism or chemical warfare.

GENERALLY AVOID: Additive hypotensive effects may occur when phosphodiesterase-5 (PDE5) inhibitors such as tadalafil are used with alcohol, as both are mild systemic vasodilators. In clinical pharmacology studies, more subjects administered alcohol at a dose of 0.7 g/kg (equivalent to approximately 6 ounces of 80-proof vodka in an 80-kg male; consumed within 10 minutes in study subjects, providing blood alcohol levels of 0.08%) in combination with tadalafil 10 or 20 mg single doses had clinically significant decreases in blood pressure than with alcohol alone. There were reports of postural dizziness, and orthostatic hypotension was observed in some. When tadalafil 20 mg was administered with alcohol at a lower dose of 0.6 g/kg (equivalent to approximately 4 ounces of 80-proof vodka in an 80-kg male), orthostatic hypotension was not observed, dizziness occurred with similar frequency relative to alcohol alone, and the hypotensive effects of alcohol were not potentiated. Neither tadalafil nor alcohol affected the plasma concentrations of the other.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of tadalafil, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients taking tadalafil should avoid consuming large amounts of alcohol (for example, 5 units or more), which may increase the potential for orthostatic signs and symptoms including increase in heart rate, decrease in standing blood pressure, dizziness, and headache. It may also be appropriate to avoid consuming large amounts of grapefruit juice.

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.