Phenylephrine HCl Injection

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Overview of Phenylephrine HCl Injection

Dosage Strength of Phenylephrine HCl Injection

0.1% (1 mg/mL) 2 mL Vial

General Information

Phenylephrine is a synthetic sympathomimetic amine with selectivity for the alpha-1-adrenergic receptor. Phenylephrine lacks significant inotropic and chronotropic effects. Phenylephrine is used orally and intranasally to treat nasal congestion. Use in younger children has been associated with an increased risk of serious adverse effects; as a result, the FDA issued a public health advisory recommending that OTC cough and cold products not be used in infants and children < 2 years of age. Parenterally, phenylephrine may reduce heart rate and cardiac output as a reflex response to its potent vasopressor effects, which is the rationale for its use to treat paroxysmal supraventricular tachycardia. Since it is a potent vasoconstrictor, phenylephrine injection can be used as a vasopressor; however the predominance of alpha-effects and lack of beta-1 inotropic effects limits the use of phenylephrine for the treatment of shock states. Phenylephrine injection was FDA-approved in December 2012.

Mechanisms of Action

Phenylephrine is a potent vasoconstrictor. It possesses both direct and indirect sympathomimetic effects. Phenylephrine is used parenterally to achieve cardiovascular effects. The dominant effect is agonism at alpha-adrenergic receptors (direct effect). In therapeutic doses, the drug has no substantial stimulant effect on the beta-adrenergic receptors of the heart (beta1-adrenergic receptors), although activation of these receptors can occur when very large doses are given. Phenylephrine does not stimulate beta-adrenergic receptors of the bronchi or peripheral blood vessels (beta2-adrenergic receptors). It is believed that alpha-adrenergic effects result from inhibition of cyclic adenosine-3′,5′-monophosphate (cAMP) production through inhibition of the enzyme adenyl cyclase, whereas beta-adrenergic effects result from stimulation of adenyl cyclase activity. Phenylephrine also releases norepinephrine from its nerve terminal storage sites (indirect effect). Although the manufacturer reports that there is no decrease in effectiveness with repeated injections of phenylephrine, some investigators have reported that tachyphylaxis can develop. Phenylephrine lacks direct inotropic and chronotropic effects on the heart. The main effect of systemic doses is vasoconstriction, resulting in constriction of most vascular beds including renal, splanchnic, and pulmonary blood vessels. Pulmonary vascular resistance may increase and a slight reduction in cardiac output may occur. Reflex bradycardia may occur, which can be reversed by atropine.

Phenylephrine may be used to treat paroxysmal supraventricular tachycardia based on its effects to reduce heart rate as a reflex mechanism in response to its alpha-1-agonist vasoconstrictive effects.

Contraindications / Precautions

Phenylephrine, particularly when administered intravenously, should be avoided in patients with severe organic cardiac disease including coronary artery disease (e.g., angina, history of myocardial infarction, acute myocardial infarction) and dilated cardiomyopathy. Phenylephrine injection is contraindicated in patients with severe hypertension and/or ventricular tachycardia. This may include patients with arrhythmias associated with tachycardia (atrial fibrillation, atrial flutter, ventricular fibrillation) because of its detrimental cardiovascular effects in these conditions (i.e., increased myocardial oxygen demand, chronotropy, proarrhythmic potential, and vasoactivity). Phenylephrine injection should be used with caution in patients with bradycardia or AV block. All forms of phenylephrine should be used with caution in patients with uncontrolled hypertension due to the increased likelihood of adverse cardiac events. Phenylephrine can cause a decrease in cardiac output, and extreme caution should be used when administering the drug, parenterally or orally, to patients with arteriosclerosis, to elderly patients, or to patients with coronary artery disease or heart failure.

Phenylephrine should be avoided in patients with cerebrovascular disease such as cerebral arteriosclerosis, aneurysm, intracranial bleeding, history or stroke or organic brain syndrome because of the potential sympathomimetic (presumably alpha) effects in the CNS and the potential for cerebrovascular hemorrhage, especially with intravenous use.

Phenylephrine should be avoided in patients with sulfite hypersensitivity unless the patient is being treated for an emergent condition such as anaphylaxis or cardiac arrest. Phenylephrine formulations contain sodium metabisulfite, a sulfite that can cause severe allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes in susceptible patients. The overall presence of sulfite hypersensitivity in the general population is unknown but presumed to be low. Sulfite hypersensitivity is seen most often in asthmatic patients compared to non-asthmatic patient.

Systemic phenylephrine products should be used with caution in men with symptomatic, benign prostatic hypertrophy, due to the potential for urinary retention.

Use phenylephrine with caution in patients with extensive peripheral vascular disease. Phenylephrine can cause excessive peripheral and visceral vasoconstriction and ischemia to vital organs.

Monitor renal function closely in patients with septic shock. If used for septic shock, phenylephrine can increase the need for renal replacement therapy.

Use caution when administering phenylephrine to patients with hepatic disease. Dose-response data indicate decreased responsiveness to phenylephrine in patients with liver cirrhosis. Larger doses may be needed in patients with hepatic disease.

Use caution when administering phenylephrine to patients with end stage renal disease. Dose-response data indicate increased responsiveness to phenylephrine in these patients. Lower doses may be needed in patients with renal failure.

Use phenylephrine with caution in patients with autonomic neuropathy. Patients with autonomic dysfunction, such as those with spinal cord injury, may have an increased blood pressure response to adrenergic drugs.


Phenylephrine is classified as FDA pregnancy category C. It should be used during pregnancy with caution. Topically applied phenylephrine is expected to provide reduced exposure systemically versus oral or injectable routes. Systemic phenylephrine must be used only when the benefit to the mother outweighs the risk to the fetus during late pregnancy, labor, or obstetric delivery; when used during this time it can cause fetal anoxia and/or bradycardia due to increased uterine contractility or decreased uterine blood flow. Obstetricians should also be aware of the risk of severe persistent hypertension if it is used during labor and delivery and the possibility of rupture of a cerebral blood vessel in the postpartum period.


It is not known whether phenylephrine is distributed into breast milk; however, the low molecular weight of the drug would suggest possible passage. According to the manufacturer, caution should be exercised when administering it to women who are breastfeeding their infants. However, since phenylephrine is generally poorly absorbed, the potential overall absorption by an infant following breastfeeding may be minimal. In the treatment of nasal congestion, non-systemic decongestant preparations such as intranasal sodium chloride or temporary use of intranasal decongestants should be considered prior to consideration of an oral decongestant. Consider the benefits of breastfeeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breastfeeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.


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.

Adverse Reactions / Side Effects

Phenylephrine is a powerful vasoconstrictor, and parenteral administration causes a rise in systolic and diastolic pressures (i.e., hypertension), which may be accompanied by myocardial ischemia (i.e., angina) and/or marked reflex sinus bradycardia and AV block. An increased workload on the heart increases the risk of heart failure. Headache may be a sign of hypertension that can be relieved by administration of an alpha-adrenergic blocking agent (e.g., phentolamine). In general, geriatric patients are more susceptible than younger adults to a reduction in cardiac output following sinus bradycardia.

Contact dermatitis has been associated with phenylephrine, with cross-sensitivity to ephedrine.

Nervous system adverse reactions associated with phenylephrine therapy, especially parenteral routes of administration, include anxiety, excitability, paresthesias, tremor, headache, and restlessness.

Nausea, vomiting, and abdominal pain have been reported with the injectable formulation of phenylephrine. Mild nausea or stomach upset may occur with non-prescription oral use at usual doses for congestion, but such adverse effects are not frequent. Ischemic colitis (bowel ischemia) has been rarely associated with the use of sympathomimetics, even oral phenylephrine, and may present with symptoms of abdominal pain and bloody diarrhea. Colitis may result from reversible splanchnic arterial vasoconstriction.

Dyspnea, pulmonary edema, and rales have been reported with the use of injectable phenylephrine.


Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

Injection Tutorial

Learn how to prepare medication for self-administered injection.


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