Pseudoephedrine (Sudafed)

Generic Name

Pseudoephedrine hydrochloride

Brand Names

Sudafed

Sudogest

Nexafed

Zephrex-D

Silfedrine

Sinutab

Sudafed Congestion

Actifed (combination with triprolidine)

Common in combination products (e.g., pseudoephedrine + cetirizine, loratadine, ibuprofen, diphenhydramine)

Drug Class

Sympathomimetic amine

Nasal decongestant

Alpha and beta adrenergic receptor agonist

Mechanism of Action

Pseudoephedrine acts primarily as an indirect sympathomimetic

It causes the release of endogenous norepinephrine from postganglionic nerve terminals and stimulates alpha-adrenergic receptors on the smooth muscle of blood vessels

The vasoconstrictive effect on the nasal mucosa reduces tissue hyperemia, edema, and nasal congestion

It also has mild beta-adrenergic effects, leading to bronchodilation and increased heart rate at higher doses

Unlike phenylephrine, pseudoephedrine is well absorbed orally and has better bioavailability

Indications

Approved Indications

Nasal congestion due to common cold, allergic rhinitis, sinusitis

Eustachian tube congestion

Temporary relief of sinus congestion/pressure

Adjunct in otitis media to promote drainage of Eustachian tubes

Combination therapy in allergic rhinitis, cold and flu products

Off-Label Uses

Prevention of barotrauma during air travel (ear congestion)

Stress incontinence (in women, rarely used now)

Narcolepsy-related cataplexy (historical)

Dosage and Administration

Adults and Children ≥12 Years

Immediate-release: 60 mg orally every 4–6 hours as needed

Extended-release: 120 mg every 12 hours or 240 mg once daily

Maximum: 240 mg per 24 hours

Children 6–11 Years

Immediate-release: 30 mg every 4–6 hours

Maximum: 120 mg per 24 hours

Use of extended-release tablets not recommended for children under 12

Children 2–5 Years

Use with caution

Dosage based on weight and specific product labeling

Generally discouraged due to risk of adverse effects

Not for use in children under 2 years

Administration

Oral tablets, caplets, or syrups

May be taken with or without food

Avoid taking close to bedtime due to stimulant effects

Pharmacokinetics

Absorption

Well absorbed orally

Onset: 15–30 minutes

Peak plasma concentration: 1–3 hours (IR), 4–6 hours (ER)

Distribution

Widely distributed

Minimal plasma protein binding

Metabolism

Partially metabolized in the liver via N-demethylation

Predominantly excreted unchanged in urine

Elimination

Renal excretion of 43% to 96% as unchanged drug

Half-life: 5–8 hours (can be prolonged in acidic urine or renal impairment)

Contraindications

Hypersensitivity to pseudoephedrine or other sympathomimetics

Severe hypertension

Severe coronary artery disease

Concomitant or recent use (within 14 days) of monoamine oxidase inhibitors (MAOIs)

Urinary retention

Narrow-angle glaucoma

Hyperthyroidism (relative contraindication)

Uncontrolled diabetes mellitus

Severe arrhythmias

Warnings and Precautions

Cardiovascular Risks

May raise blood pressure and heart rate

Caution in patients with controlled hypertension or cardiac disease

Avoid in patients with arrhythmias, ischemic heart disease, or uncontrolled hypertension

CNS Stimulation

May cause nervousness, excitability, insomnia, or anxiety

Caution in psychiatric disorders, insomnia, or seizure disorders

Prostatic Hypertrophy

May worsen urinary retention in men with benign prostatic hyperplasia (BPH)

Avoid or monitor closely

Thyroid Dysfunction

Use cautiously in hyperthyroidism due to risk of exaggerated sympathomimetic effects

Renal Impairment

Dose adjustment may be required due to renal elimination

Accumulates in renal dysfunction

Pediatric Risks

Increased risk of adverse effects in young children including agitation, hallucinations, and even death

Avoid in children under 2 years and use caution in those under 6

Pregnancy and Lactation

Pregnancy (Category C)

Limited human data

Potential risk of vasoconstriction and reduced placental blood flow

Avoid in first trimester if possible

May be used short-term in 2nd or 3rd trimester if benefits outweigh risks

Lactation

Excreted in breast milk in small amounts

May cause irritability and decreased milk supply

Use with caution in breastfeeding women

Adverse Effects

Common

Insomnia

Nervousness

Headache

Tachycardia

Palpitations

Dry mouth

Nausea

Less Common

Dizziness

Restlessness

Hypertension

Anxiety

Tremors

Rare but Serious

Atrial fibrillation

Myocardial infarction

Seizures

Urinary retention

Psychosis (especially in children and elderly)

Overdose

Symptoms

Agitation

Tachycardia

Hypertension

Seizures

Hallucinations

Hyperthermia

Management

Supportive care

Activated charcoal if early

Sedation for agitation

Beta-blockers may be used for severe hypertension

Avoid acidifying the urine to increase excretion unless advised by toxicology

Drug Interactions

Monoamine Oxidase Inhibitors (MAOIs)

Risk of hypertensive crisis

Avoid for 14 days after discontinuing MAOI

Other Sympathomimetics (e.g., phenylephrine, ephedrine)

Additive effects

Increased risk of hypertension and arrhythmia

Beta-blockers

Can blunt antihypertensive effects

May lead to unopposed alpha-adrenergic stimulation and increased blood pressure

Tricyclic Antidepressants (e.g., amitriptyline)

Potentiation of cardiovascular stimulation

Caffeine and other stimulants

Additive CNS stimulation

Increased risk of insomnia, palpitations, tremors

Antihypertensive drugs

Reduced efficacy (especially alpha-blockers and beta-blockers)

Linezolid (MAOI-like antibiotic)

Potential for hypertensive reactions

Avoid concurrent use

Use in Special Populations

Elderly

More sensitive to cardiovascular and CNS side effects

Use with caution

Start with lower doses

Children

Avoid under age 2

Use lowest effective dose with close monitoring

Patients with ADHD or Anxiety Disorders

May exacerbate restlessness, insomnia, or agitation

Monitoring Parameters

Blood pressure and pulse in hypertensive or cardiac patients

Sleep disturbance or agitation if used chronically

Monitor urinary symptoms in males with BPH

Assess CNS symptoms in pediatric or geriatric patients

Regulatory Controls and Sales Restrictions

Abuse Potential

Used in illicit synthesis of methamphetamine

Regulated under Combat Methamphetamine Epidemic Act (CMEA) in the US

Sales limited to 3.6 g/day and 9 g/month per individual

Requires ID, signature, and sale recordkeeping

Available behind-the-counter (BTC) in many countries

Comparative Pharmacology

Pseudoephedrine vs Phenylephrine

Pseudoephedrine has better oral bioavailability and decongestant efficacy

Phenylephrine less effective due to first-pass metabolism

Pseudoephedrine more likely to cause CNS and cardiac stimulation

Pseudoephedrine vs Oxymetazoline (topical)

Oxymetazoline provides more rapid nasal relief but with risk of rebound congestion

Pseudoephedrine avoids local tachyphylaxis and rhinitis medicamentosa

Formulations Available

Oral tablets: 30 mg, 60 mg (IR), 120 mg, 240 mg (ER)

Syrup and liquid: typically 15 mg/5 mL or 30 mg/5 mL

Combination formulations with antihistamines, NSAIDs, cough suppressants, expectorants, and antipyretics

Common combos:

• Loratadine + Pseudoephedrine

• Cetirizine + Pseudoephedrine

• Ibuprofen + Pseudoephedrine

• Diphenhydramine + Pseudoephedrine