Phenylephrine vs. pseudoephedrine: Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

There are many contributing factors to nasal congestion and sinus pressure, most notably seasonal allergic rhinitis and the common cold. Nasal and sinus pressure can impair nasal breathing, lead to headaches, and decrease productivity. Phenylephrine (Sudafed PE) and pseudoephedrine (Sudafed) are two types of decongestants that may be effective in relieving sinus pressure. These drugs work by directly stimulating adrenergic receptors in the nasal passage, as well as other parts of the body. While they are similar in some ways, there are some key differences that may determine which one is the right decongestant for you.

What are the main differences between phenylephrine and pseudoephedrine?

Phenylephrine (What is Phenylephrine?) is a nasal decongestant available by itself or in a variety of combination cold and flu products. It is available over-the-counter (OTC), and does not require a prescription or logging of purchase information. Phenylephrine is a potent alpha-adrenergic agonist and has virtually no beta-adrenergic agonist activity. Alpha-adrenergic receptors, when stimulated, are responsible for the constriction of blood vessels. Beta-adrenergic receptors, when stimulated, are responsible for the relaxation of blood vessels, and also cause an increase in heart rate. While it causes some vasoconstriction in the nasal passageway which may relieve sinus pressure, it also causes vasoconstriction throughout the body which may increase blood pressure. Phenylephrine is available in oral preparations as a tablet or liquid, as well as an injectable solution. The injectable solution would only be administered in a healthcare setting.

Pseudoephedrine (What is Pseudoephedrine?) is a nasal decongestant which is also available by itself or in a variety of combination cold and flu products. It is available without a prescription, but its purchase is restricted to varying degrees. Each state, in combination with federal guidelines, determines the purchase limits for its consumers. Purchases of pseudoephedrine must occur at a pharmacy counter with a pharmacist present and are logged into a database. These restrictions now exist because pseudoephedrine is a key ingredient in the illegal manufacturing of methamphetamine.

Pseudoephedrine stimulates alpha-adrenergic receptors in the nasal mucosa, as well as beta-adrenergic receptors throughout the body. This leads to nasal decongestion and bronchial relaxation, but also leads to increased heart rate and contractility. It is available in oral preparations as a tablet or liquid, as well as an injectable solution. The injectable solution would only be administered in a healthcare setting.

Conditions treated by phenylephrine vs. pseudoephedrine

There is an injectable form of phenylephrine approved to treat hypotension, or very low blood pressure, in situations related to shock or anesthesia. This dosing is typically administered as an injection in a healthcare setting where a patient is being monitored by a physician and other healthcare providers. It is also used off-label, without FDA approval, to treat ischemic priapism (an erection in males that has lasted too long). The over-the-counter dosage form of phenylephrine is used as a nasal decongestant.

Pseudoephedrine is approved to treat nasal congestion.

Is phenylephrine or pseudoephedrine more effective?

At one time, pseudoephedrine was essentially the only nasal decongestant on the market. However, when sales of the product began to be restricted, manufacturers looked to reformulate their products with another active ingredient so that they could remain on store shelves and easily purchased. Phenylephrine then became the oral decongestant found in products that could be purchased without going to the pharmacy counter to have your purchase logged by the pharmacist.

The increased use of phenylephrine prompted researchers to evaluate if its decongestant effects were as potent as those of pseudoephedrine. In a randomized, placebo-controlled study, patients with seasonal allergic rhinitis were exposed to grass pollen in the Vienna Challenge Chamber. They received either phenylephrine, pseudoephedrine, or a placebo to alleviate their congestive symptoms. The study concluded that there was no significant difference between phenylephrine and placebo. However, pseudoephedrine provided a significant difference in nasal decongestion as compared to both placebo and phenylephrine. These results suggest that pseudoephedrine is the superior nasal decongestant.

Some researchers have expressed concern that our desire to curtail the manufacturing of methamphetamine by restricting the sales of pseudoephedrine has led to an inferior product (phenylephrine) being widely used in its place.

Many times, the treatment of rhinitis and sinus pressure may be more effective if other agents are used in combination. Antihistamines, for instance, will slow the production of mucus and may augment the effects of nasal decongestants.

Coverage and cost comparison of phenylephrine vs. pseudoephedrine

Phenylephrine in its oral, over-the-counter form does not require a prescription. It is typically not covered by Medicare or other commercial insurance plans. The average cost for Sudafed PE is around $6-$8 when purchased over-the-counter, but if your doctor writes a prescription, you may be able to fill it at the pharmacy for as low as $5.96 with a coupon from SingleCare.

Pseudoephedrine, although restricted to purchase at a pharmacy, is also an OTC drug. If your doctor writes a prescription for pseudoephedrine, you will be able to obtain the quantity they prescribe even if it is higher than the state limit for over-the-counter purchases.

Pseudoephedrine is typically not covered by Medicare or other commercial insurance plans, though a select few may if a prescription is written. The average cost for 24 tablets of Sudafed 30 mg ranges from $6-$10 when purchased over-the-counter If your doctor writes a prescription, you may be able to fill the generic at the pharmacy for as low as $2.53 with a coupon from SingleCare.

Get the SingleCare prescription discount card

Common side effects of phenylephrine vs. pseudoephedrine

Phenylephrine and pseudoephedrine are both adrenergic agonists and have some of the same side effects, though their difference in affinity for alpha- and beta-adrenergic receptors are responsible for some differences.

Phenylephrine and pseudoephedrine are known to cause anxiety, dizziness, headache, insomnia, nervousness, and restlessness. In addition, pseudoephedrine has been documented to cause tachycardia, palpitations, arrhythmia, blurred vision, and anorexia. It is difficult to define how frequently these side effects can occur.

Patients with high blood pressure or other known cardiac conditions should not use pseudoephedrine without guidance from their physician.

The following table is not intended to be a complete list of side effects. You should consult a pharmacist or other healthcare professional for a complete list.

Source: DailyMed (phenylephrine) DailyMed (pseudoephedrine)

Drug interactions of phenylephrine vs. pseudoephedrine

Phenylephrine and pseudoephedrine have a very similar drug interaction profile due to their adrenergic effects on the alpha and beta receptors. Alpha-blockers, such as tamsulosin, may diminish the vasoconstrictive properties of both decongestants making them less effective.

MAO inhibitors, such as selegiline, and ergot derivatives, such as bromocriptine, may enhance the hypertensive effects of the decongestants. This would be concerning in someone with pre-existing hypertension who may be considering decongestant use. The combination of phenylephrine or pseudoephedrine with either MAO inhibitors or ergot derivatives is contraindicated.

The following list is not meant to be a complete list of all potential drug interactions. Please consult your pharmacist or physician for a complete list and more information.

Warnings of phenylephrine vs. pseudoephedrine

Phenylephrine and pseudoephedrine are available without a prescription and are generally considered to be safe drugs. Due to their effects on the cardiac system, patients with high blood pressure and heart disease should not use these drugs without explicit consent from their physician. These drugs are intended for short-term use for the relief of acute rhinitis and sinus pressure. Patients who experience these symptoms for longer than seven days, or who develop a fever, should consult a physician.

Phenylephrine is in pregnancy category C which means that studies in animals showed adverse effects to the fetus. When a drug is category C, there may be some situations where the benefit to the pregnant patient outweighs the risk, and phenylephrine should not be used without consent from your physician. Pseudoephedrine is pregnancy category B which means that animal studies have not shown adverse effects to the fetus. Pseudoephedrine is considered safe to take when pregnant after consulting your physician. Pseudoephedrine should, however, be avoided in the first trimester.

Frequently asked questions about phenylephrine and pseudoephedrine

What is phenylephrine?

Phenylephrine is an over-the-counter nasal decongestant available in 5 mg and 10 mg tablets, as well as an oral solution. It is also available in an injectable form which is only used in an inpatient setting by medical professionals for low blood pressure. Phenylephrine can be purchased without restriction or logging of the purchaser’s information.

What is pseudoephedrine?

Pseudoephedrine is an over-the-counter nasal decongestant available in 30 mg and 60 mg tablets, as well as 120 mg and 240 mg extended-release tablets. It is also available as an oral solution. Pseudoephedrine purchases must be done at a pharmacy and the purchase information must be logged into a database. Purchase limits are set by state and federal guidelines.

Are phenylephrine or pseudoephedrine the same?

Phenylephrine and pseudoephedrine are both adrenergic agonists. Phenylephrine has primarily an affinity to only alpha-adrenergic receptors, while pseudoephedrine has an affinity to both alpha- and beta-adrenergic receptors. Their side effect profiles are very similar.

Is phenylephrine or pseudoephedrine better?

Studies have shown that pseudoephedrine is a much more effective decongestant than phenylephrine. Phenylephrine’s decongestant effects may not be significantly different from that of a placebo. The effects of both drugs may be augmented with concurrent use of other products that affect rhinitis, such as antihistamines.

Can I use phenylephrine or pseudoephedrine while pregnant?

Phenylephrine should not be used when pregnant unless the benefit to the mother outweighs the risk.  Pseudoephedrine is considered safe to take after the first trimester. Always consult your physician before taking a nasal decongestant when pregnant.

Can I use phenylephrine or pseudoephedrine with alcohol?

Phenylephrine and pseudoephedrine are safe to take if consuming alcohol.

Is phenylephrine a stimulant?

Phenylephrine does stimulate alpha-adrenergic receptors which may make it responsible for central nervous system stimulant effects such as restlessness, anxiety, and insomnia. It is thought that it may not cause the effects to the extent that pseudoephedrine does, however.

Who should not take phenylephrine?

Patients who have high blood pressure, pre-existing heart disease, or other cardiac conditions should not take phenylephrine without consent from their physician. There are alternative decongestant options, such as nasal sprays, which may be more appropriate in this population. Women who are pregnant should consult a physician before using phenylephrine.

Is phenylephrine a good decongestant?

Studies have shown that phenylephrine is an inferior, or less effective, decongestant than pseudoephedrine. In fact, it may offer no benefit over that of a placebo.