Phenylephrine injection is a sympathomimetic (alpha-1 adrenergic receptor agonist) that is used in the treatment of hypotension and refractory shock when administered intravenously.

Phenylephrine Uses:

• Hypotension/shock:
  • It is indicated in the treatment of hypotension, vascular failure in shock.

Note: It is not recommended for treatment of septic shock, further evidence needed as positive clinical outcome

• Guideline recommendations:
  • Cardiogenic shock:
    • According to the American Heart Association (AHA-2017)) scientific statement for the use of phenylephrine in cardiogenic Shock, It should be considered (if needed) for initial vasoactive management of cardiogenic shock due to aortic stenosis, mitral stenosis, or dynamic left ventricular outflow tract obstruction.
• Hypotension during anesthesia:
  • It is used as a vasoconstrictor in regional analgesia
• Nasal congestion:
  • It acts as a decongestant and available as a nasal over the counter drug
• Off Label Use of Phenylephrine in Adults:
  • It is used in hypotension in obstructive hypertrophic cardiomyopathy
  • Priapism

Phenylephrine Dose in Adults

Phenylephrine Dose in the treatment of Hypotension/shock:

Note: The Society of Critical Care Medicine (SCCM) recommends phenylephrine for septic shock in the following conditions:

• • Norepinephrine is the preferred first-line agent if it is associated with life-threatening arrhythmias.
  • High cardiac output with persistently low blood pressure.
  • Combination of inotrope/vasopressor and low-dose vasopressin failed to achieve target mean arterial pressure and phenylephrine is used as salvage therapy.
• IV bolus: 100 - 500 mcg per dose every 10 - 15 minutes (Maximum initial dose is 500 mcg)
• IV infusion: Initial dose: 100 - 180 mcg/minute, or alternatively, 0.5 mcg/kg/minute; titrate to desired response. Dosing of 0.4 - 9.1 mcg/kg/minute while treating septic shock.
• ACLS guideline recommendations (to treat severe hypotension [eg, systolic blood pressure <70 mm Hg] and low total peripheral resistance):
  • Cardiogenic shock (off label dose):
    • 1 - 10 mcg/kg/minute.
    • Initial dose: 0.5 - 2 mcg/kg/minute
  • Cardiogenic shock (off-label dose):
    • Note: Initially in cardiogenic shock due to aortic stenosis, mitral stenosis, or dynamic left ventricular outflow tract obstruction: 0.1 - 10 mcg/kg/minute

Phenylephrine Dose in the treatment of Hypotension during anesthesia:

• IV bolus: 40 - 100 mcg/dose every 1 - 2 minutes (Maximum total dose: 200 mcg)
• IV infusion: Initial dose: 10 - 35 mcg/minute adjusted according to blood pressure goal (not to exceed 200 mcg/minute)

Phenylephrine Dose in the treatment of Nasal congestion:

• Oral: OTC labeling: 10 mg every 4 hours as needed for ≤7 days
• Maximum: 60 mg/24 hours

Phenylephrine Dose in the treatment of Priapism (ischemic) (off-label):

• Intracavernous (off-label route): 100 - 500 mcg every 3 - 5 minutes (with concentration of 100 - 500 mcg/mL) over the course of ~1 hour;
• Use cautiously in case of cardiovascular disease, lower concentrations with smaller volumes should be given.

Phenylephrine Dose in Childrens

Note: Dosing presented in both mg (oral) and mcg (parenteral); use caution when ordering and dispensing.

Phenylephrine Dose in the treatment of Nasal congestion: Oral:

• Children 4 to 5 years:
  • 5 mg every 4 hours
  • Maximum dose: 15 mg in a day
• Children 6 to 11 years:
  • 5 mg every 4 hours
  • Maximum dose: 30 mg in a day
• Children ≥12 years and Adolescents:
  • 10 mg every 4 hours
  • Maximum dose: 60 mg in a day

Phenylephrine Dose in the treatment of Hypotension, low cardiac output:

• Infants, Children, and Adolescents:
  • IM, Subcutaneous: 100 mcg/kg/dose every 1 - 2 hours; Maximum dose: 5000 mcg
  • IV bolus: 5 - 20 mcg/kg/dose every 10 - 15 minutes; initial dose should not be more than 500 mcg; Maximum dose: 1000 mcg
  • Continuous IV infusion:
    • Usual initial dose: 0.1 - 0.5 mcg/kg/minute; titrate to desired response
    • In cases of shock/intraoperative hypotension, up to 2 mcg/kg/minute have been reported and
    • For the management of infundibular spasm, even higher doses up to 5 mcg/kg/minute may be needed.

Phenylephrine Dose in the treatment of hypotension during spinal anesthesia: IM, Subcutaneous:

• Infants, Children, and Adolescents:
  • 44 - 88 mcg/kg/dose
  • Maximum dose: 500 mcg

Pregnancy Risk Factor C

• The placenta can be crossed by phenylephrine. 
• There are no studies on animal reproduction.
• It is an over-the-counter drug that can be used to relieve nasal congestion.
• However, it should not be taken during pregnancy.
• Phenylephrine does not have a strong association with an increased risk for fetal adverse reactions in the first trimester.
• The dose and duration of therapy are not listed in any publications.
• Avoid oral phenylephrine during the first trimester
• Anesthesia-induced hypotension is prevented or treated by injecting phenylephrine during caesarean section delivery.
• Phenylephrine is more beneficial than ephedrine for the fetus, and has a lower emetic potential.

Use of phenylephrine during breastfeeding

• It is not known if breast milk contains phenylephrine
• Phenylephrine should not be used in lactating mothers.
• It is best to weigh the risks to infants and the benefits to mother before making a decision about whether to use it.
• If a lactating mother is concerned, the manufacturer suggests caution.

Phenylephrine Dose in Kidney Disease:

No dosage adjustment is recommended.   

Dose in Liver disease:

No dosage adjustment is recommended.   

Side effects of phenylephrine Injection:

• Cardiovascular:
  • Cardiac Arrhythmia (Rare)
  • Exacerbation Of Angina
  • Hypertension
  • Hypertensive Crisis
  • Ischemia
  • Localized Blanching
  • Low Cardiac Output
  • Peripheral Vasoconstriction (Severe)
  • Reflex Bradycardia
  • Visceral Vasoconstriction (Severe)
  • Worsening Of Heart Failure
• Central Nervous System:
  • Anxiety
  • Dizziness
  • Excitability
  • Headache
  • Insomnia
  • Nervousness
  • Paresthesia
  • Precordial Pain (Or Discomfort)
  • Restlessness
• Dermatologic:
  • Pallor
  • Piloerection
  • Pruritus
• Endocrine & Metabolic:
  • Metabolic Acidosis
• Gastrointestinal:
  • Epigastric Pain
  • Gastric Irritation
  • Nausea
  • Vomiting
• Genitourinary:
  • Decreased Renal Blood Flow
  • Decreased Urine Output
• Hypersensitivity:
  • Hypersensitivity Reaction (Including Skin Rash
  • Urticaria
  • Leukopenia
  • Agranulocytosis
  • Thrombocytopenia)
• Neuromuscular & Skeletal:
  • Neck Pain
  • Tremor
  • Weakness
• Ophthalmic:
  • Blurred Vision
• Respiratory:
  • Dyspnea
  • Respiratory Distress

Side effects of Oral phenylephrine:

• Central Nervous System:
  • Anxiety
  • Dizziness
  • Excitability
  • Headache
  • Insomnia
  • Nervousness
  • Restlessness

Contraindications to Phenylephrine:

• Hypersensitivity
• Hypertension severe

Injection:

• Severe hypertension; Ventricular tachycardia

Vazculep:

• The manufacturer's labeling does not list any contraindications.

Labeling over the counter (Oral)

• Self-medication: Take MAO inhibitor therapy with you or within 14 days.

Warnings and precautions

• Cardiovascular effects
  • IV: This can lead to severe bradycardia, and a decrease in cardiac output due the increase in cardiac afterload.
  • Patients with severe coronary disease may also experience angina and pulmonary arterial hypertension.
  • Follow these instructions with caution
    • Preexisting bradycardia
    • Partial heart block
    • Myocardial Disease
    • Grave coronary artery disease
    • Heart failure or cardiogenic shock (extreme care recommended).
    • Peripheral Vasoconstriction: This can cause vasoconstriction in the peripheral and visceral areas and may lead to ischemia of vital organs.
  • You should monitor your blood pressure and adjust the infusion rate.
• Extravasation:
  • Avoid extravasation during intravenous administration
• Acidosis:
  • Acidosis may have a reduced effectiveness, so it is recommended that acidosis be corrected before using.
• Autonomic dysfunction
  • An autonomic dysfunction such as spinal cord injury may cause an exaggerated response in blood pressure.
• Hyperthyroidism:
  • Hyperthyroidism should be treated with caution

Phenylephrine (systemic): Drug Interaction

Monitoring parameters:

• Blood pressure (or MAP)
• Heart rate
• cardiac output
• Intravascular volume status
• Pulmonary capillary wedge pressure (as appropriate)
• infusion site monitoring

How to administer Phenylephrine?

IV:

• Hypotension and shock: It can be given as:
  • an IV bolus (intermittent) over 20 - 30 seconds OR
  • Continuous infusion (after diluting): central line is preferred for administration. An infusion pump may be required
• Anesthesia-induced hypotension :
  • It is given as an IV bolus over 20 - 30 seconds.

To avoid extravasation, confirm proper needle or catheter placement.

Extravasation management:

• Stop infusion immediately, disconnect and leave cannula/needle in place
• Aspirate the extravasated solution then remove needle/cannula and elevate extremity
• Initiate phentolamine (or alternative antidote)
• Apply dry warm compresses

Phentolamine:

• 5 - 10 mg in 10 - 20 ml normal saline into extravasation site as soon as possible, can be re-administered if needed

Alternative to phentolamine:

• Nitroglycerin topical 2% ointment (limited data available): Apply a 1-inch strip to the site of ischemia; can be repeated every 8 hours if necessary.   

Mechanism of action of Phenylephrine:

• It acts as an alpha-adrenergic receptor agonist and is a potent systemic artery vasoconstrictor.
• Phenylephrine causes a rise in systemic vascular resistance.
• It also produces a dose-dependent elevation of blood pressure (both diastolic as well as systolic), and reduces heart rate.

The onset of action:

• Blood pressure increase or vasoconstriction
  • IM, Subcutaneous: 10 - 15 minutes
  • IV: Immediate
• Nasal decongestant: Oral: 15 - 30 minutes

Duration:

• Blood pressure increase or vasoconstriction
  • IM: 1 - 2 hours
  • IV: ~15 - 20 minutes
  • Subcutaneous: 50 minutes
• Nasal decongestant: Oral: ≤4 hours

Absorption: Oral:

• Erratic and incomplete.

Metabolism: Hepatic via

• oxidative deamination (Oral: 24%; IV: 50%) and
• Undergoes sulfation (Oral - mostly within the gut wall): 46%; IV: 8%
• and some glucuronidation; forms inactive metabolites

Bioavailability:

• Oral: ≤38%

Half-life elimination:

• Alpha phase: ~5 minutes;
• Terminal phase: 2 - 3 hours

Time to peak:

• Oral: 0.75 - 2 hours

Excretion:

• Through Urine

International Brand Names of Phenylephrine:

• Little Colds Decongestant
• Medi-Phenyl
• Nasal Decongestant
• Non-Pseudo Sinus Decongestant
• Sudafed PE Childrens
• Sudafed PE Congestion
• Sudogest PE
• Vazculep
• Neo-Synephrine
• AK-Dilate
• Albalon Relief
• Davinefrina
• Denason
• Drosyn
• Efrin-10
• Ethifrin
• Fadalefrina
• Fenilefrina
• Fenylefrinhydroklorid
• Humex Nosni
• Humoxal
• Irifrin
• Isonefrine
• Isopto Frin
• Metaoxedrin
• Midfrin
• Midriafen
• Minims Phenylephrine HCL 10%
• Minims Phenylephrine Hydrochloride
• Mydfrin
• Nasenspray
• Nefrisol
• Neo-Sinefrina
• Neo-Synephrine
• Neo-Synephrine Ophthalmic
• Neosinicin
• Neosynephrin-POS
• Neosynephrine Faure 10%
• Oftan-Metaoksedrin
• OQ-Dilat
• Prefrin
• Qura Nasal
• Visadron
• We Li Ang

Phenylephrine Brand Names in Pakistan: