Introduction
Pseudoephedrine is a sympathomimetic amine commonly used as a nasal decongestant. It is available in both prescription and over-the-counter formulations, though many jurisdictions now regulate its sale due to its potential use in illicit methamphetamine production. Pseudoephedrine has been clinically used for decades and remains an effective option for temporary relief of nasal and sinus congestion caused by common colds, allergies, and upper respiratory infections.
Mechanism of Action
Pseudoephedrine acts primarily as an alpha-adrenergic receptor agonist, with particular selectivity for α-adrenergic receptors in the mucosal blood vessels of the respiratory tract. By stimulating these receptors, pseudoephedrine causes vasoconstriction, which reduces blood flow to nasal mucosa and decreases tissue edema and inflammation. This results in shrinkage of swollen nasal mucous membranes and reduction of tissue hyperemia, edema, and nasal congestion. Pseudoephedrine has minimal beta-adrenergic activity and does not significantly affect bronchial smooth muscle.
Indications
- Temporary relief of nasal congestion due to common cold, hay fever, or other upper respiratory allergies
- Relief of sinus congestion and pressure
- Promotes nasal or sinus drainage
- Adjuvant therapy in acute otitis media (to improve Eustachian tube patency)
Dosage and Administration
Adults and children ≥12 years: 60 mg every 4-6 hours, not to exceed 240 mg in 24 hours Children 6-12 years: 30 mg every 4-6 hours, not to exceed 120 mg in 24 hours Children 4-6 years: 15 mg every 4-6 hours, not to exceed 60 mg in 24 hours Special Populations:- Renal impairment: Use with caution; consider reduced dosing
- Hepatic impairment: Use with caution
- Elderly: May be more sensitive to effects; consider lower doses
- Pregnancy: Category C - use only if potential benefit justifies potential risk
- Lactation: Excreted in breast milk; use with caution
Pharmacokinetics
Absorption: Well absorbed from gastrointestinal tract; bioavailability approximately 100% Distribution: Widely distributed throughout body tissues; crosses blood-brain barrier and placenta Metabolism: Partially metabolized in liver by N-demethylation Elimination: Primarily excreted unchanged in urine (80-90%); elimination half-life 9-16 hours; urinary excretion is pH-dependent (increased in acidic urine) Onset of action: 30 minutes Duration of action: 4-6 hours (immediate release); 12-24 hours (extended release)Contraindications
- Hypersensitivity to pseudoephedrine or any component of the formulation
- Patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping MAOI therapy
- Severe hypertension
- Severe coronary artery disease
- Uncontrolled hyperthyroidism
- Urinary retention
Warnings and Precautions
- Use with caution in patients with hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, prostatic hypertrophy, or increased intraocular pressure
- May cause CNS stimulation and insomnia
- Risk of medication misuse due to stimulant properties
- Potential for abuse in individuals with substance use disorders
- May cause dizziness; caution patients about driving or operating machinery
- Use beyond 7 days for cold symptoms or 3 days for fever should be evaluated by healthcare provider
Drug Interactions
- MAOIs: Risk of hypertensive crisis
- Beta-blockers: May antagonize cardiac effects
- Other sympathomimetics: Additive effects, increased risk of adverse reactions
- Antihypertensives: May decrease effectiveness
- Ergot alkaloids: Increased vasoconstrictive effects
- Theophylline: Increased theophylline levels
- Urinary acidifiers: May increase pseudoephedrine elimination
- Urinary alkalinizers: May decrease pseudoephedrine elimination
Adverse Effects
Common (≥1%):- CNS: Nervousness, dizziness, insomnia, restlessness
- Cardiovascular: Tachycardia, palpitations
- Gastrointestinal: Nausea, vomiting, anorexia
- Other: Dry mouth, headache, difficulty urinating
- Cardiovascular: Hypertension, arrhythmias, angina, myocardial infarction
- CNS: Hallucinations, seizures, psychoses
- Allergic: Rash, urticaria, anaphylaxis
Monitoring Parameters
- Blood pressure and heart rate regularly, especially in patients with cardiovascular risk factors
- Symptom relief and need for continued therapy
- Signs of CNS stimulation or adverse effects
- Renal function in patients with pre-existing renal impairment
- Signs of misuse or abuse in at-risk populations
Patient Education
- Take exactly as directed; do not exceed recommended dosage
- May cause drowsiness or dizziness; use caution when driving or operating machinery
- Avoid caffeine-containing products as they may increase nervousness and insomnia
- Report rapid heartbeat, dizziness, or difficulty urinating to healthcare provider
- Do not use for more than 7 days unless directed by healthcare provider
- Store safely away from potential misuse
- Be aware that purchase may be restricted or require identification in many jurisdictions
References
1. Simons FE, Simons KJ. Clinical pharmacology of H1-antihistamines. Clin Allergy Immunol. 2002;17:141-78. 2. Hatton RC, Winterstein AG, McKelvey RP, et al. Efficacy and safety of oral phenylephrine: systematic review and meta-analysis. Ann Pharmacother. 2007;41(3):381-390. 3. FDA Drug Safety Communication: Serious blood pressure increases with over-the-counter pseudoephedrine. January 2018. 4. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2023. 5. Pseudoephedrine. In: Lexicomp Online [database]. Hudson, OH: Wolters Kluwer Clinical Drug Information, Inc.; 2023. 6. Horak F, Zieglmayer P, Zieglmayer R, et al. A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber. Ann Allergy Asthma Immunol. 2009;102(2):116-120.