Sympathomimetic (α-agonist nasal decongestant)
Pseudoephedrine is a nasal decongestant used to temporarily relieve nasal and sinus congestion in colds and allergies. It is available without prescription, but should be used with care in people with high blood pressure, heart or thyroid disease.
Also known as: Sudafed, pseudoefedrina, pseudoephedrine
DailyMed/FDA (NIH/NLM) — OTC Pseudoephedrine label (Drug Facts): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8c4c786c-2b0f-4a23-a87d-effbcfe0c857
OTC DailyMed label (Drug Facts): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8c4c786c-2b0f-4a23-a87d-effbcfe0c857 — pharmacokinetics: PubMed PMID 7507589 (Kanfer et al., Pharmacokinetics of oral decongestants, 1993); PMID 7438686 (Brater et al., Renal excretion of pseudoephedrine, 1980)
Decongestant + theophylline: additive stimulation and hypokalaemia.
Theophylline and pseudoephedrine (a sympathomimetic, isomer of ephedrine) are both CNS and cardiovascular stimulants. The theophylline label documents the combination with ephedrine as having "synergistic CNS effects, with increased frequency of nausea, nervousness, and insomnia" — the same class as pseudoephedrine. Together they increase the risk of tachycardia, palpitations, tremor, anxiety and insomnia, and in susceptible patients may precipitate arrhythmias or seizures (theophylline lowers the seizure threshold). The combination is frequent in over-the-counter cold/flu products — always ask the patient about decongestants. Use with caution, prefer topical decongestants or a reduced theophylline dose, and watch for adrenergic symptoms, especially in the elderly and cardiac patients.
Pseudoephedrine + theophylline: additive CNS and cardiovascular stimulation — nausea, nervousness, insomnia, tachycardia and tremor. Use with caution.
Additive stimulant effects (tachycardia, tremor) and possible potassium loss.
Potassium and adrenergic symptoms.
Palpitations, tremor, insomnia.
Watch for cardiovascular symptoms; monitor potassium in at-risk patients.
DailyMed (FDA) — approved Pseudoephedrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=78faa497-6743-b85b-e053-2a91aa0ae822 ; approved Theophylline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e64036a-ee3e-42e7-9e59-881f88a4e298 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Decongestant + SSRI: possible increased pressor effect.
Pseudoephedrine is a sympathomimetic with vasoconstrictor and pressor effects; fluoxetine can potentiate the adrenergic effects (tachycardia, hypertension, tremor) and there is also a theoretical risk of serotonin syndrome from the serotonergic component of pseudoephedrine. The interaction is mild in most patients, but caution is recommended in hypertensive, cardiac and hyperthyroid patients: monitor blood pressure, use the lowest dose and shortest duration of the decongestant, and prefer non-sympathomimetic alternatives (nasal corticosteroids, saline) when possible.
Decongestant + SSRI: possible increased pressor effect. Monitor blood pressure and adrenergic symptoms.
Additive sympathomimetic effect in patients on SSRIs (risk of hypertension/tachycardia).
Blood pressure.
Hypertension, palpitations.
Monitor blood pressure and heart rate.
DailyMed (FDA) — approved Pseudoephedrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=78faa497-6743-b85b-e053-2a91aa0ae822 ; approved Fluoxetine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09fb3100-1e06-4cdc-8016-7e4f5d097490 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Decongestant + SSRI: possible increased pressor and serotonergic effect.
Pseudoephedrine has a sympathomimetic effect (vasoconstriction, tachycardia) and sertraline, as an SSRI, can potentiate the adrenergic effects and theoretically increase the risk of serotonin syndrome. In most patients the interaction is mild and self-limited, but in hypertensive, cardiac or elderly patients monitor blood pressure and adrenergic symptoms (palpitations, tremor, agitation). Use the decongestant at the lowest dose and for the shortest time, preferring local alternatives (nasal corticosteroids) in at-risk patients.
Decongestant + SSRI: possible increased pressor and serotonergic effect. Monitor blood pressure.
Pseudoephedrine may add a pressor effect; the SSRI interferes with metabolism.
Blood pressure in at-risk patients.
Hypertension, agitation, tremor.
Monitor blood pressure and serotonergic symptoms.
DailyMed (FDA) — approved Pseudoephedrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=78faa497-6743-b85b-e053-2a91aa0ae822 ; approved Sertraline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=91e24d17-ff0a-449c-9472-b9df74c98456 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Decongestant + β2-agonist: additive sympathetic effects.
Pseudoephedrine is a sympathomimetic with alpha and beta activity (vasoconstriction and cardiac stimulation) and salbutamol a beta2-agonist; the adrenergic overlap adds up the cardiovascular effects — raised blood pressure (alpha), tachycardia and tremor (beta) — and salbutamol may also "produce significant hypokalaemia... with the potential to produce adverse cardiovascular effects" (salbutamol label). The combination is frequent in cold formulations in asthmatic patients and is particularly relevant in hypertensives, cardiac patients and hyperthyroidism. Prefer topical decongestants, use the lowest doses and monitor blood pressure, heart rate and potassium in at-risk patients.
Pseudoephedrine + salbutamol: alpha/beta-adrenergic overlap — raised blood pressure, tachycardia, tremor and hypokalaemia. Watch for cardiovascular symptoms.
Overlapping α/β-adrenergic effects raise blood pressure and heart rate.
Blood pressure and heart rhythm.
Hypertension, palpitations, tremor.
Use with caution in cardiovascular patients; watch for symptoms.
DailyMed (FDA) — approved Pseudoephedrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=78faa497-6743-b85b-e053-2a91aa0ae822 ; approved Salbutamol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3236f82c-14e9-dfd4-e063-6294a90ac43d — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Sympathomimetic decongestant + antiarrhythmic: risk of arrhythmias and pressor effect.
Pseudoephedrine is a sympathomimetic that increases heart rate and automaticity; in patients treated with amiodarone (which prolongs QT and is frequently associated with underlying heart disease), the risk of tachycardias and ventricular extrasystoles increases. Pseudoephedrine should be avoided in patients with known arrhythmias or ischaemic heart disease; if used, limit the duration, watch for symptoms (palpitations, chest pain) and prefer non-sympathomimetic alternatives (e.g. nasal corticosteroids, antihistamines) for nasal congestion.
Pseudoephedrine + amiodarone: the sympathomimetic effect of pseudoephedrine increases the arrhythmia risk in patients on amiodarone. Avoid or use with caution.
Pseudoephedrine (α-agonist) raises blood pressure and cardiac work, risking arrhythmia in predisposed patients.
Blood pressure and ECG.
Hypertension, tachycardia, arrhythmias.
Avoid in cardiovascular disease; if used, monitor BP and rhythm.
DailyMed (FDA) — approved Pseudoephedrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=78faa497-6743-b85b-e053-2a91aa0ae822 ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Alcohol may potentiate the cardiovascular effects.
Limit alcohol intake.
EMC-UK (MHRA) — approved Pseudoephedrine SmPC: https://www.medicines.org.uk/emc/product/8292/smpc
Caffeine may potentiate the stimulant effects of pseudoephedrine (tachycardia, insomnia).
Limit caffeine intake, especially at night.
EMC-UK (MHRA) — approved Pseudoephedrine SmPC: https://www.medicines.org.uk/emc/product/8292/smpc
Pseudoephedrine may precipitate angle-closure glaucoma crisis.
Contraindicated in angle-closure glaucoma.
EMC-UK (MHRA) — approved Pseudoephedrine SmPC: https://www.medicines.org.uk/emc/product/8292/smpc
Hyperthyroidism potentiates sympathomimetic effects.
Use with caution; avoid in uncontrolled hyperthyroidism.
EMC-UK (MHRA) — approved Pseudoephedrine SmPC: https://www.medicines.org.uk/emc/product/8292/smpc
Pseudoephedrine may precipitate angina and arrhythmias in ischaemic heart disease.
Contraindicated in active coronary disease.
EMC-UK (MHRA) — approved Pseudoephedrine SmPC: https://www.medicines.org.uk/emc/product/8292/smpc
Pseudoephedrine (α-agonist) may markedly raise blood pressure.
Contraindicated in severe uncontrolled hypertension.
EMC-UK (MHRA) — approved Pseudoephedrine SmPC: https://www.medicines.org.uk/emc/product/8292/smpc
Avoid in the 1st trimester (limited data); use the lowest dose for the shortest time.
Use only if clearly necessary and with caution.
Limited data; prefer to avoid during breastfeeding.
No specific additional contraception.
EMC-UK (MHRA) — approved Pseudoephedrine SmPC: https://www.medicines.org.uk/emc/product/8292/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Peripheral sympathomimetic (predominant alpha-1 adrenergic agonist) that constricts the vessels of the nasal and sinus mucosa, reducing congestion and oedema. Relief of nasal congestion is the established therapeutic effect; central (stimulant) action is minimal compared with ephedrine.
Pseudoephedrine activates alpha-1 adrenergic receptors of the respiratory mucosa, causing arteriolar vasoconstriction, decreased blood flow and mucosal oedema. At therapeutic oral doses the beta and central effects are of little relevance.
Pseudoephedrine is well absorbed orally, with plasma peaks 1–2 hours after the dose; oral bioavailability is ~90% (extended-release tablets have later peaks). Plasma protein binding is minimal.
Pseudoephedrine is metabolised to a small extent in the liver (N-demethylation); it is excreted predominantly unchanged in the urine (43–96% of the dose), by glomerular filtration and tubular secretion. Renal excretion depends strongly on urinary pH — alkalinisation increases tubular reabsorption and prolongs the half-life (from 1.9 to up to 21 hours).
The elimination half-life in adults is ~4–8 hours (mean ~5.4 hours), dependent on urinary pH (1.9 hours with acid urine up to ~21 hours with alkaline urine); in children it is ~3.1 hours.
