Phenylephrine
Phenylephrine, sold under the brand names Neosynephrine and Sudafed PE among others, is a medication used as a decongestant for uncomplicated nasal congestion in the form of a nasal spray or oral tablet, intravenously in cases of low blood pressure, or as a suppository to relieve hemorrhoids. It can also be applied to the skin.
Common side effects when taken by mouth or injected include nausea, vomiting, headache, and anxiety. Use on hemorrhoids is generally well tolerated. Severe side effects may include a slow heart rate, intestinal ischemia, chest pain, kidney failure, and tissue death at the site of injection. It is unclear whether its use during pregnancy and breastfeeding is safe. Phenylephrine is a selective α1-adrenergic receptor agonist with minimal to no β-adrenergic receptor agonist activity or induction of norepinephrine release. It causes constriction of both arteries and veins.
Phenylephrine was patented in 1933 and came into medical use in 1938. It is available as a generic medication. Unlike pseudoephedrine, abuse of phenylephrine is very uncommon. Its effectiveness as an oral nasal decongestant has been questioned. In 2023, a U.S. Food and Drug Administration panel concluded that the drug was ineffective as a nasal decongestant when taken orally, performing no better than placebo. In November 2024, the FDA proposed to remove oral phenylephrine as an active ingredient that can be used in over-the-counter monograph drug products for the temporary relief of nasal congestion.
Medical uses
Decongestant
Phenylephrine is used as an alternative to pseudoephedrine as a decongestant, the availability of which has been restricted in some countries due to a potential for use in the illicit synthesis of methamphetamine. Its efficacy as an oral decongestant has been questioned, with several independent studies finding that it provided no more relief to sinus congestion than a placebo.A 2007 meta-analysis concluded that the evidence for its effectiveness is insufficient, though another meta-analysis published shortly thereafter by researchers from GlaxoSmithKline found the standard 10-mg dose to be more effective than a placebo; however, the fact that GSK markets many products containing phenylephrine has raised some speculation regarding selective publishing and other controversial techniques. A 2007 study by Wyeth Consumer Healthcare notes that 7 studies available in 1976 support the efficacy of phenylephrine at a 10 mg dosage. The Food and Drug Administration withdrew the indication "for the temporary relief of nasal congestion associated with sinusitis" in 2007.
Two studies published in 2009 examined the effects of phenylephrine on symptoms of allergic rhinitis by exposing people to pollen in a controlled, indoor environment. Neither study was able to distinguish between the effects of phenylephrine and a placebo. Pseudoephedrine and loratadine–montelukast therapy were found to be significantly more effective than both phenylephrine and placebo.
Pseudoephedrine was previously much more commonly available in the United States. However, provisions of the Combat Methamphetamine Epidemic Act of 2005 placed restrictions on the sale in the United States of pseudoephedrine products to prevent the clandestine manufacture of methamphetamine. Since 2004, phenylephrine has been increasingly marketed as a substitute for pseudoephedrine; some manufacturers have changed the active ingredients of products to avoid restrictions on sales. Phenylephrine has been off-patent for some time, and many generic brands are available.
In September 2023, an independent advisory committee to the U.S. Food and Drug Administration unanimously agreed that there is insufficient evidence showing that "orally administered phenylephrine is effective as a nasal decongestant". The committee also unanimously believes that this does not need further study. The FDA responded to the committee, stating it would take its advice under advisement. In November 2024, the FDA proposed to remove oral phenylephrine as an active ingredient that can be used in over-the-counter monograph drug products for the temporary relief of nasal congestion.
Hemorrhoids
are caused by swollen veins in the rectal area. Phenylephrine can be used topically to prevent symptoms of hemorrhoids. Phenylephrine causes the constriction of vascular smooth muscle and is often used in the treatment of hemorrhoids to narrow the swollen veins and relieve the attendant pain. However, veins contain less vascular smooth muscle in their walls than arteries. Products for treatment may also include substances that will form a protective barrier over the inflamed area, resulting in less pain when feces are passed.Phenylephrine hydrochloride at 0.25% is used as a vasoconstrictor in suppository formulations for hemorrhoid treatment.
Pupil dilation
Phenylephrine is used as an eye drop to dilate the pupil to facilitate visualization of the retina. It is often used in combination with tropicamide as a synergist when tropicamide alone is not sufficient. Narrow-angle glaucoma is a contraindication to phenylephrine use. As a mydriatic, it is available in 2.5% and 10% eye drops. Phenylephrine eye drops are applied to the eye after a topical anesthetic is applied.Intraocular bleeding
Phenylephrine has been used as an intracameral injection into the anterior chamber of the eye to arrest intraocular bleeding occurring during cataract and glaucoma surgery.Low blood pressure
Phenylephrine is commonly used as a vasopressor to increase the blood pressure in unstable patients with hypotension, especially resulting from septic shock. Such use is common in surgery and anesthesia or critical-care practices; it is especially useful in counteracting the hypotensive effect of epidural and spinal anesthesia, as well as the vasodilating effect of bacterial toxins and the inflammatory response in sepsis and systemic inflammatory response syndrome.Because of its vasoconstrictive effect, phenylephrine can cause severe necrosis if it infiltrates the surrounding tissues. Because of this, it should be given through a central line if at all possible. Damage may be prevented or mitigated by infiltrating the tissue with the alpha-blocker phentolamine by subcutaneous injection.
In clinical studies, intravenous phenylephrine increases blood pressure, decreases cardiac output, increases cerebral blood flow, and decreases cerebral tissue oxygen saturation. The decreases in cardiac output, increases in cerebral blood flow, and decreases in cerebral tissue oxygen saturation with phenylephrine are all related to the degree of blood pressure increase. The decrease in cardiac output is primarily due to a decrease in heart rate and a modest decrease in stroke volume. The decrease in heart rate is due to activation of the arterial baroreflex, which regulates heart rate in response to changes in blood pressure. Because of the decrease in cardiac output, phenylephrine is a negative inotropic agent. Its effects on cardiac output and cerebral oxygenation are unfavorable, and on account of this, the use of phenylephrine in the treatment of intraoperative hypotension is now being recommended against and moved away from in favor of other agents without these adverse effects like ephedrine and dopamine.
When taken orally, phenylephrine has a threshold dose of about 50mg to affect the cardiovascular system, a dose at which the drug decreases heart rate and slightly increases arterial blood pressure. Additionally, an over-the-counter dose of 60mg produces a slight increase in heart rate with no detectable changes in blood pressure. However, other literature reports that doses over 15mg affect the cardiovascular system, including increases in blood pressure and decreases in heart rate. Higher doses, like 150mg, more robustly affect the cardiovascular system.
Other uses
Phenylephrine has been used in the treatment of postural orthostatic tachycardia syndrome. It has been found to improve vascular resistance, enhance circulatory support, and improve symptoms of orthostatic intolerance in people with the condition. It has been described as particularly effective in people with neuropathic POTS. However, phenylephrine has not been specifically approved for the treatment of POTS, and data on this use are limited. This is also the case with other medications used in the treatment of POTS.Phenylephrine has been used in the treatment of priapism.
Available forms
Phenylephrine is available in the form of oral tablets and syrups for use as a nasal decongestant, as an intravenous solution to treat hypotension, as an ophthalmic solution, spray, or eye drop to cause pupil dilation, and as a cocoa butter suppository, among other forms. It was also previously available as a metered aerosol for inhalation, but this formulation was discontinued.Phenylephrine is available both alone and in combination with other drugs. These other drugs include antihistamines like chlorpheniramine, doxylamine, promethazine, and mepyramine ; analgesics like paracetamol, ibuprofen, ketorolac, and codeine; cough suppressants like dextromethorphan; expectorants like guiafenesin; anticholinergics like cyclopentolate and tropicamide; and β-adrenergic receptor agonists like isoprenaline. It is used in combination with antihistamines and analgesics in cough and cold preparations, with anticholinergics in ophthalmic formulations, and with β-adrenergic receptor agonists in inhalational forms. Intravenous phenylephrine is always formulated by itself.