Phenylephrine Hydrochloride

Approved Indications:

• Hypotension:
• Treatment of hypotension during anesthesia.
• Management of shock-associated hypotension (e.g., septic shock) in adults.
• Nasal Congestion (Topical/Nasal Route):
• Temporary relief of nasal congestion due to common cold, sinusitis, or allergies.
• Ophthalmic Use:
• Mydriasis induction (pupil dilation) before eye examinations or surgical procedures.
• Management of posterior synechiae and uveitis.
• Hemorrhoid Relief (Rectal Formulations):
• Symptomatic relief of hemorrhoidal swelling, burning, and itching.

Off-label or Clinically Accepted Uses:

• Priapism:
• Intracavernosal injection for treatment of ischemic priapism.
• Acute Angle-Closure Glaucoma (as adjunct):
• Used with other agents to lower intraocular pressure temporarily.

Adults:

• Hypotension (IV):
• Initial: 100–180 mcg/min IV bolus; maintenance: 40–60 mcg/min infusion, titrated to BP.
• Alternative bolus: 0.5–1 mg every 10–15 minutes as needed.
• Nasal Decongestant (Nasal Spray):
• 0.25% to 1% solution: 2–3 sprays or drops in each nostril every 4 hours as needed.
• Max duration: Not to exceed 3 consecutive days.
• Ophthalmic Use:
• 2.5% or 10% ophthalmic solution: 1 drop per eye, usually before procedures.
• Rectal (Hemorrhoids):
• Apply up to 4 times daily, especially after bowel movements and before bedtime.

Pediatrics:

• Nasal Decongestant (≥6 years):
• 0.125%–0.25% solution: 1–2 drops per nostril every 4 hours.
• Avoid in children <2 years unless prescribed.

Elderly:

• Start at the lower end of dosing range; increased sensitivity to vasopressors.

Renal/Hepatic Impairment:

• Use with caution; no specific dose adjustments, but titrate based on response.

Administration:

• IV: Dilute appropriately, administer via central or large peripheral vein.
• Nasal/Ophthalmic: For topical use only; avoid oral ingestion.
• Rectal: External application; avoid internal use unless specified.

Phenylephrine Hydrochloride is a selective alpha-1 adrenergic receptor agonist. It causes vasoconstriction of arterioles and veins by stimulating alpha-1 receptors, leading to an increase in systemic vascular resistance and blood pressure. In nasal and ocular applications, it constricts local blood vessels, thereby reducing mucosal edema or dilating pupils, respectively. Unlike epinephrine or norepinephrine, it has minimal beta-adrenergic activity, making it less chronotropic and less arrhythmogenic.

• Absorption:
• Oral bioavailability is low (~38%) due to first-pass metabolism.
• Rapid absorption when administered intranasally, intravenously, or ophthalmically.
• Distribution:
• Widely distributed in body tissues.
• Volume of distribution: ~340 L (IV).
• Metabolism:
• Primarily metabolized in the liver via monoamine oxidase (MAO).
• Excretion:
• Excreted mostly in urine (primarily as inactive metabolites).
• Elimination half-life (IV): ~2.5–3 hours.
• Onset (IV): Within minutes; Duration: ~15–20 minutes.

• Pregnancy:
• FDA Category C (use with caution; animal studies have shown adverse effects, no adequate human data).
• Vasoconstrictive properties may reduce uterine blood flow—use only if benefits outweigh risks.
• Lactation:
• Excretion into breast milk is unknown.
• Use with caution; may reduce milk supply due to vasoconstrictive effect on mammary tissue.
• Monitor for irritability or reduced feeding in infants.

• Primary Class: Sympathomimetic (Vasopressor/Decongestant)
• Subclasses:
• Selective Alpha-1 Adrenergic Agonist
• Non-catecholamine vasopressor
• Ophthalmic mydriatic agent (topical)

• Known hypersensitivity to phenylephrine or any formulation components
• Severe hypertension or ventricular tachycardia
• Angle-closure glaucoma (ophthalmic use)
• Monoamine oxidase inhibitor (MAOI) use within the past 14 days
• Severe coronary artery disease or uncontrolled hyperthyroidism (relative contraindications)

• Cardiovascular: Use with caution in patients with hypertension, arrhythmias, heart failure, or bradycardia.
• Endocrine: Caution in hyperthyroidism due to increased sensitivity.
• Neurological: May worsen cerebrovascular disease due to vasoconstriction.
• Prolonged Nasal Use: Risk of rebound congestion (rhinitis medicamentosa).
• Pediatric Risk: Use cautiously; systemic absorption can cause significant cardiovascular effects.
• Elderly: Higher sensitivity to vasopressors; monitor BP and perfusion.
• Ophthalmic Use: Avoid use with narrow-angle glaucoma; 10% solution may cause significant BP rise.

Common Adverse Effects:

• Cardiovascular:
• Hypertension, reflex bradycardia, arrhythmias, palpitations
• CNS:
• Headache, anxiety, dizziness, restlessness, insomnia
• Gastrointestinal:
• Nausea, vomiting
• Local (Nasal/Ophthalmic):
• Burning, stinging, rebound congestion (nasal)
• Photophobia, eye irritation (ophthalmic)

Serious/Rare Effects:

• Hypertensive crisis
• Myocardial ischemia or infarction
• Pulmonary edema
• Cerebral hemorrhage
• Severe bradycardia or cardiac arrest (especially with high IV doses)

• MAO Inhibitors: Potentiate hypertensive crisis; contraindicated within 14 days.
• Beta-blockers: May enhance vasopressor effect or cause bradycardia.
• Tricyclic Antidepressants: Enhance pressor response.
• Digoxin: Increased risk of arrhythmias.
• Ergot Alkaloids: Additive vasoconstrictive effects.
• Anesthetic Agents (e.g., Halothane): May sensitize myocardium to arrhythmogenic effects.

Enzyme Involvement:

• Metabolized by monoamine oxidase (MAO); no significant CYP450 interaction.

• 2024 (FDA/EMA): Reinforced cautions regarding pediatric nasal formulations due to increased systemic absorption and cardiovascular side effects.
• Ongoing Recommendations:
• Limit use of 10% ophthalmic phenylephrine to settings with appropriate cardiovascular monitoring.
• Nasal phenylephrine efficacy as a decongestant has been questioned in some systematic reviews; clinicians advised to evaluate alternatives in certain populations.

• IV Solution:
• Store at 20°C to 25°C (68°F to 77°F).
• Protect from light and freezing.
• Use immediately after dilution; discard unused portion.
• Nasal/Ophthalmic Formulations:
• Store between 15°C and 30°C (59°F to 86°F).
• Protect from light.
• Do not freeze.
• Rectal Preparations:
• Store at room temperature (20°C to 25°C).
• Avoid excessive heat and moisture.