Phenylephrine can potentiate the effects and increase the toxicity of other sympathomimetics including cocaine by adding to their sympathomimetic activity. Although no data are available, phenylephrine should be used cautiously in patients using significant quantities of amphetamines, cocaine, or other sympathomimetic-containing products.
Concurrent use of dronabinol, THC or nabilone with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Caution is advisable during co-administration of these agents.
Caffeine is a CNS-stimulant, and, although data are lacking with phenylephrine, concurrent administration may produce excessive stimulatory effects such as nervousness, irritability, insomnia, or tremor. Other xanthines, such as theophylline, aminophylline or dyphylline can interact in a similar way. Excessive caffeine ingestion should be avoided while taking phenylephrine concurrently. This includes ingestion of foods and beverages that contain high amounts of caffeine such as coffee, teas, green tea, colas, and chocolate and dietary supplements such as guarana.
MAOIs, or drugs that possess MAO-inhibiting activity such as furazolidone, linezolid, or procarbazine, can prolong and intensify the cardiac stimulation and vasopressor effects of sympathomimetics. Phenelzine and tranylcypromine appear to produce the greatest risk since these two MAOIs also have intrinsic amphetamine-like activity. In the presence of MAOIs, phenylephrine and other drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. Although it is unclear if selegiline (inhibitor of MAO type B) can predispose to this reaction, caution is advised for concurrent use of phenylephrine with any MAO-inhibiting drug. Phenylephrine should not be administered during or within 14 days following the use of most MAOIs or drugs with MAO-inhibiting activity. However, rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; serious reactions with sympathomimetics are not ordinarily expected. However, because a case of elevated blood pressure occurred during use of rasagiline and a sympathomimetic ophthalmic preparation, caution is advised when rasagiline is administered with sympathomimetics.
Ergot alkaloids should not be administered with vasoconstrictors such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, and pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Amphetamines and phentermine, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines or phentermine may be advisable. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
The coadministration of oxytocin with medications that can induce vasoconstriction, such as phenylephrine, may result in severe persistent hypertension.
The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by reserpine, alpha-blockers, beta-blockers, central-acting adrenergic agents (e.g., clonidine, guanfacine, guanabenz, methyldopa), and mecamylamine. Use with caution in patients receiving other antihypertensive drug classes [e.g., angiotensin II receptor antagonists, angiotensin-converting enzyme inhibitors (ACE inhibitors), calcium-channel blockers, diuretics] as well. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure (especially systolic hypertension) has been reported in some patients. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. Prior administration of a beta-blocker has been shown to potentiate phenylephrine’s vasoconstricting effects. Phenylephrine has been postulated to occupy, but not stimulate, beta2-receptors in blood vessels. Beta-blockers therefore may occupy these receptors and effectively increase the quantity of the drug available for stimulation of alpha receptors. The effect of unopposed alpha vasoconstriction can result in hypertension and/or reflex bradycardia. The effect may be more likely to occur with non-selective beta-blockers like propranolol. While diuretics can cause decreased arterial responsiveness to vasopressor amines (e.g., norepinephrine, phenylephrine), the effect is not sufficient to preclude their coadministration.
Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Concomitant use of tricyclic antidepressants with sympathomimetics, such as phenylephrine, should be avoided whenever possible; use with caution when concurrent use cannot be avoided. Concomitant use may result in increased risk for cardiovascular toxicity or severe headaches.
Sympathomimetics such as phenylephrine may interact with maprotiline, resulting in severe cardiovascular effects including arrhythmias, severe hypertension, hyperpyrexia, and/or severe headaches.
Concomitant use of nitrates with systemic sympathomimetics, including phenylephrine, can result in antagonism of the antianginal effects of the nitrate.
Drug interactions with St. John’s wort, Hypericum perforatum are unclear at this time. Some of the components of this herb have been shown to inhibit monoamine oxidase (MAO) in vitro, but in vivo activity is unclear. If St. John’s wort does have MAOI-like activities, it could potentially increase the cardiac stimulation and vasopressor effects of the sympathomimetics. St. John’s wort should be used cautiously with any sympathomimetic agent.
The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.