Drug Interactions between aminophylline / ephedrine / guaifenesin / phenobarbital and silodosin

MONITOR: Barbiturates may decrease serum levels and therapeutic effects of the methylxanthines. The mechanism is barbiturate induction of CYP450 3A4 and 1A2 hepatic metabolism of methylxanthines.

MANAGEMENT: Close observation for clinical and laboratory evidence of decreased methylxanthine effect is indicated if these drugs must be used together. Patients should be advised to notify their physician if they experience a worsening of their respiratory symptoms.

MONITOR: Coadministration with inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may decrease the plasma concentrations of silodosin, which is a substrate of both the isoenzyme and efflux transporter.

MANAGEMENT: The potential for diminished pharmacologic effects of silodosin should be considered during coadministration with CYP450 3A4 and/or P-gp inducers. Alternative treatments may be required if an interaction is suspected.

MONITOR: Theoretically, the pharmacologic effects of agents that act through agonism at the alpha receptor may be antagonized by those that act via antagonism at the same receptor, and vice versa. Alpha-1 agonists and alpha agonists with beta-agonist effects exert opposing effects on vascular tone and blood pressure than alpha-1 antagonists. Some of these agents act on both alpha-1 and alpha-2 receptors, though they may have a stronger affinity for one or the other. The severity of the interaction may also be influenced by the degree of systemic absorption of each agent.

MANAGEMENT: Monitoring for diminished effects on blood pressure and vasoconstriction is recommended if an alpha-agonist (e.g., epinephrine, norepinephrine, ephedrine, metaraminol) is coadministered with an alpha-antagonist (e.g., phentolamine, phenoxybenzamine, terazosin). If the concomitant alpha agonist being used also acts on beta receptors, the effects of unopposed beta stimulation should also be considered.

Ephedrine-methylxanthine combinations are used for the treatment of asthma but the efficacy of the combination has been questioned. This combination may lead to increased xanthine side effects. The mechanism is unknown, but may be related to synergistic pharmacologic effects. Patients using this combination should be closely monitored for side effects such as nausea, vomiting, tachycardia, nervousness, or insomnia. If side effects are noted, the dosage of the xanthine may need to be decreased.