What is the effect of Phenylephrine, an alpha-1 (α1) adrenergic receptor agonist?

From the Guidelines

Phenylephrine should be used with caution due to its potential side effects and limited efficacy as an oral decongestant, and its use should be carefully considered in patients with certain medical conditions, such as hypertension, heart disease, and hyperthyroidism.

Key Points to Consider

• Phenylephrine is a decongestant medication that works by narrowing blood vessels in the nasal passages, reducing swelling and congestion, as noted in the study by 1.
• It's commonly found in over-the-counter cold and allergy medications, typically in doses of 10mg for oral tablets taken every 4 hours as needed (not exceeding 60mg in 24 hours).
• For nasal sprays, the concentration is usually 0.25% to 1%, used every 4 hours as needed for no more than 3 consecutive days to avoid rebound congestion.
• Phenylephrine works by activating alpha-1 adrenergic receptors, causing vasoconstriction in the nasal mucosa.
• However, recent studies have questioned its effectiveness when taken orally, as it undergoes significant first-pass metabolism in the liver, potentially reducing its clinical benefit, as discussed in 1.
• Side effects may include increased blood pressure, headache, dizziness, and nervousness.
• People with high blood pressure, heart disease, diabetes, or thyroid disorders should consult a healthcare provider before using phenylephrine, as should pregnant or breastfeeding women.
• It should not be used with MAO inhibitors due to potential dangerous interactions.

Important Considerations

• The study by 1 highlights the importance of using phenylephrine with caution, especially in patients with certain medical conditions.
• The potential for side effects, such as increased blood pressure and nervousness, should be carefully considered when using phenylephrine.
• The limited efficacy of phenylephrine as an oral decongestant should also be taken into account when deciding whether to use this medication.

From the FDA Drug Label

No adverse effects on the offspring were reported when pregnant rats were treated via a single daily intravenous bolus dose of up to 200 mcg/day phenylephrine hydrochloride (0.2 times the HDD based on body surface area) from Gestation Day 6 to Lactation Day 20.

Phenylephrine has been studied in pregnant rats, and no adverse effects on the offspring were reported at doses of up to 200 mcg/day. However, the safety and effectiveness in pediatric patients have not been established.

• The use of phenylephrine in pregnant women has been observed in 26 literature-based studies in the perioperative setting, including low-risk pregnant women undergoing neuraxial anesthesia during cesarean delivery.
• Increases in systolic and mean blood pressure following administration of phenylephrine were observed in these studies.
• However, no conclusion can be drawn about the safety of phenylephrine in human pregnancy due to the lack of direct evidence from the FDA label. 2

From the Research

Phenylephrine Overview

• Phenylephrine is a widely used medication for the treatment of nasal congestion, but its efficacy at certain doses is not well established 3.
• The Food and Drug Administration has requested further studies to assess the efficacy and safety of phenylephrine hydrochloride (PE HCl) 3.

Efficacy of Phenylephrine

• A study found that PE HCl, at doses of up to 40 mg every 4 hours, is not significantly better than placebo at relieving nasal congestion in adults with seasonal allergic rhinitis 3.
• However, another study found that a single oral dose of phenylephrine 10 mg is effective as a decongestant in adults with acute nasal congestion associated with the common cold 4.
• The efficacy of phenylephrine may depend on the specific condition being treated and the dose used.

Safety of Phenylephrine

• Phenylephrine was well tolerated at doses of up to 30 mg in a study of adults with seasonal allergic rhinitis 3.
• Common adverse events associated with phenylephrine include headache, with at least one treatment-emergent adverse event experienced by 18.4% of participants 3.
• The safety of phenylephrine in hypertensive patients is not well established, with some studies suggesting that it may have non-significant effects on blood pressure when used at recommended oral doses as a nasal decongestant 5.

Comparison to Other Decongestants

• Pseudoephedrine is another commonly used decongestant, which has been found to be effective in treating symptoms of the common cold and flu, but also has potential risks and side effects 6.
• A study found that sustained-release pseudoephedrine appears safe for medically controlled hypertensive patients, but may have an upward trend in blood pressure and heart rate parameters 7.