Phenylephrine Hydrochloride

Class: alpha-Adrenergic Agonists
VA Class: AU100
CAS Number: 61-76-7
Brands: Benadryl, Excedrin, Neo-Synephrine, Preparation H, Sudafed PE, Theraflu, Triaminic, Tylenol, Vicks

Introduction

Sympathomimetic amine that predominantly acts by a direct effect on α-adrenergic receptors.

Uses for Phenylephrine Hydrochloride

Shock

Used to produce vasoconstriction as an adjunct to correct hemodynamic imbalances in the treatment of shock that persists after adequate fluid volume replacement.^b (See Contraindications and also see Warnings under Cautions.)

Individual hemodynamic abnormalities must be identified and monitored so that therapy can be adjusted as necessary.^b

May be ineffective if severe peripheral vasoconstriction exists and may have a deleterious effect by causing further reductions in plasma volume and blood flow to vital organs.^b

Value of pressor therapy in shock, especially when due to septicemia, burns, trauma, or drug overdosage, is questionable;^b may be indicated if patient fails to respond to administration of fluids, a change in position or other measures directed to the specific cause of shock, such as anti-infectives in septicemia, epinephrine in anaphylactic shock, or specific antidotes and/or removal of the drug in cases of overdosage. Drugs which also stimulate the myocardium (e.g., norepinephrine, metaraminol) are usually preferred to phenylephrine, especially in shock caused by myocardial infarction, septicemia, or surgical complications.^b

Pressor therapy in overdosage of barbiturates or other sedatives is especially controversial; some clinicians have stated that the incidence of mortality may actually be increased when a pressor is given.^b

May be useful when cardiac stimulation is undesirable (as in the treatment of hypotension occurring during general anesthesia with cyclopropane, halothane, or other agents that sensitize the myocardium to arrhythmias).^b

May be used to treat hypotension or shock resulting from overdosage of or idiosyncratic reactions to certain drugs (e.g., adrenergic and ganglionic blocking agents, rauwolfia and veratrum alkaloids, phenothiazines).^b

May be useful to control shock following pheochromocytomectomy, but shock generally can be prevented by maintenance of adequate blood volume and/or preoperative administration of an α-adrenergic blocking agent.^b

Hypotension During Spinal Anesthesia

Has been used both for the prevention and treatment of hypotension resulting from spinal anesthesia, but some clinicians state that pure α-adrenergic agonists should not be used because they may further reduce cardiac output.^b

Routine prophylactic use of any vasopressor in spinal anesthesia has been questioned because hypotension does not always occur during spinal anesthesia and treatment can readily be instituted if necessary; it has been suggested that vasopressors be administered prophylactically only in those cases in which a substantial decrease in BP is expected.^b

Use of vasopressors to correct hypotension occurring during anesthesia in obstetrical patients is controversial; hypotension can usually be minimized by adequate hydration and changing the position of the patient so that the uterus does not compress the inferior vena cava; if a vasopressor is required, ephedrine is usually preferred.^b

Prolongation of Local Anesthesia

May be added to solutions of some local anesthetics to decrease the rate of vascular absorption of the anesthetic, thereby localizing anesthesia and prolonging the duration of anesthesia.^b

Decreases risk of systemic toxicity due to the local anesthetic.^b

Not as effective as epinephrine in prolonging local anesthesia but may be preferred when cardiostimulation is undesirable.^b

Paroxysmal Supraventricular Tachycardia

Administered IV to raise BP in order to terminate some attacks of paroxysmal supraventricular tachycardia, especially in patients who are also hypotensive or in shock.^b

Administration of an anticholinesterase drug having a short duration of action (e.g., edrophonium chloride) may be safer.^b

Nasal Congestion

Self-medication for temporary relief of nasal congestion associated with upper respiratory allergy (e.g., hay fever) or the common cold.^{114 124} However, efficacy of oral phenylephrine for this use has been questioned.^{115 125 126 127}

Self-medication for temporary relief of sinus congestion and pressure.^{114 124}

Used in fixed combination with other agents (e.g., acetaminophen, chlorpheniramine, dextromethorphan, diphenhydramine, guaifenesin, pheniramine) for temporary relief of nasal/sinus congestion and/or other symptoms (e.g., rhinorrhea, sneezing, lacrimation, itching eyes, oronasopharyngeal itching, cough) associated with seasonal or perennial allergic rhinitis, other upper respiratory allergies, or the common cold.^{133 134 135 136 137 138 139}

Because of recent state and federal actions restricting OTC sale and purchase of preparations containing pseudoephedrine, ephedrine, or phenylpropanolamine (no longer commercially available in the US),^{109 110 111 112} some manufacturers have reformulated various OTC preparations by substituting phenylephrine for pseudoephedrine that was previously contained in these preparations.^{113 116}

Labeled and has been used for self-medication for temporary relief of nasal congestion associated with sinusitis;^{114 117} however, efficacy data are lacking and/or controversial.^{117 118 119} In October 2005, FDA issued a final rule to remove this indication from labeling of OTC nasal decongestants.¹¹⁷ Compliance date for preparations with annual sales <$25,000 was October 11, 2007; compliance date for all other preparations was April 11, 2007.¹¹⁷

Hemorrhoids

Anorectal preparations (e.g., creams, gels, ointments, suppositories) containing phenylephrine hydrochloride are used topically or rectally to provide temporary symptomatic relief of external or internal hemorrhoids.^{101 102 103 104 105 106 107 108}

When applied topically or rectally to the anorectal area, vasoconstrictors such as phenylephrine stimulate α-adrenergic receptors in the vascular beds¹⁰² with a resultant temporary constriction of arterioles and a modest and transient reduction in congestion (swelling) of hemorrhoidal tissues.^{101 102 108}

May relieve anorectal pruritus, discomfort, and irritation, possibly in part secondary to some weak local anesthetic action; the mechanism of this local anesthetic effect is unknown.^{102 108}

May relieve pruritus associated with histamine release.^{102 108}

If minor bleeding is present, a clinician should be consulted promptly for advice since anorectal bleeding may be a sign of conditions ranging in seriousness from simple abrasions to cancer.¹⁰⁸

Diagnosis of Heart Murmurs

IV phenylephrine has been used to increase BP as an aid in the diagnosis of heart murmurs†.^b

Phenylephrine Hydrochloride Dosage and Administration

General

• 
  

  Vasopressor therapy: Elevate BP to slightly less than the patient’s normal BP.^b

  
  


• 
  

  Previously normotensive patients: SBP should be maintained at 80–100 mm Hg.^b

  
  


• 
  

  Previously hypertensive patients: SBP should be maintained at 30–40 mm Hg below their usual BP.^b

  
  


• 
  

  Very severe hypotension: Maintenance of even lower BP may be desirable if blood or fluid volume replacement has not been completed.^b

  
  


• 
  

  Do not leave patients receiving the drug by IV infusion unattended; the infusion flow rate must be closely monitored; check BP frequently, especially during IV administration.^b

  
  


• 
  

  Continue therapy until adequate BP and tissue perfusion are maintained.^b

  
  


• 
  

  IV infusion discontinuance: Gradually slow the infusion rate and avoid abrupt withdrawal.^b

  
  


• 
  

  Observe patient carefully so that therapy may be resumed if the BP falls too rapidly.^b

  
  


• 
  

  Do not reinstate pressor therapy until the SBP falls to 70–80 mm Hg; some patients may require additional administration of IV fluids before discontinuation.^b

  
  

Administration

Parenteral Administration

Vasopressor therapy: Administer by IM, sub-Q, or slow IV injection or IV infusion; route of administration determined by the needs of the individual patient.^b

Patients who are in shock may require IV administration to ensure absorption.^b Usually administered by IV infusion as a dilute solution.^b

Direct IV injections are administered in treating paroxysmal atrial or nodal tachycardia or in emergencies requiring a strong, immediate pressor effect.^b

Emergencies: May be administered by direct IV injection.^b

Dilution

For convenience in administration by direct IV injection, 1 mL of the commercially available phenylephrine hydrochloride injection containing 10 mg/mL may be diluted with 9 mL of sterile water for injection to prepare a solution containing 1 mg/mL.^b

For IV infusion, phenylephrine may be diluted with 5% dextrose or 0.9% sodium chloride injection.^b

The concentration of phenylephrine and the infusion rate depend on the drug and fluid requirements of the individual patient. Infusion solutions are usually prepared by adding 10 mg of phenylephrine hydrochloride to 500 mL of diluent.

Oral Administration

Vasoconstrictor for nasal congestion: Administer orally alone^{114 124} or as a fixed-combination decongestant preparation.^b

Place orally dissolving strip(s) on the tongue, where it rapidly dissolves and then can be swallowed.¹²⁴

Topical and Rectal Administration

Vasoconstrictor for hemorrhoidal symptoms: Topical preparations are administered externally to the affected perianal area, and rectal preparations are administered externally to the affected perianal area and/or intrarectally.^{101 102 103 104 105 106 107 108}

Apply topical preparations labeled for external use only externally to the affected area and do not administer inside the rectum by either using fingers or any mechanical device or applicator.^{101 102 103 105 107}

Rectal preparations are labeled either for rectal use only (e.g., suppositories) or for external and/or intrarectal use only.^{101 102 104 106 107}

When a special applicator such as a pile pipe or other mechanical device is used to administer the drug intrarectally, attach the applicator to the tube of drug and then lubricate the applicator well and gently insert into the rectum;^{101 102 104} cleanse the applicator thoroughly after each use and store according to the manufacturer’s instructions.¹⁰⁴

Do not use such preparations if introduction of the applicator or device into the rectum causes additional pain; advise patients to consult a clinician promptly in such cases.^{101 102 104 107}

Remove wrapper from suppositories prior to insertion into the rectum.^{101 102 106 107}

Advise patients receiving the drug for the local management of hemorrhoids to cleanse the affected perianal area by patting with warm water and mild soap and rinsing thoroughly or with an appropriate cleansing wipe whenever practical.^{101 102 103 104 105 106 107}

Dry the area by patting or blotting with toilet tissue or a soft cloth before application of the drug.^{101 102 103 104 105 106 107}

Dosage

Because combinations and dosage strengths vary for fixed-combination preparations, consult manufacturer's product labeling for appropriate dosage of the specific preparation.

Pediatric Patients

Administer the lowest effective dosage for the shortest possible time; when possible, small doses should be injected initially and subsequent doses determined by pressor response.^b

Hypotension

Mild or Moderate

IM or Sub-Q

Children: 0.1 mg/kg or 3 mg/m² IM or sub-Q; may give additional IM or sub-Q doses in 1–2 hours if needed.^b

Hypotension During Spinal Anesthesia

Treatment

IM or Sub-Q

Children: 0.044–0.088 mg/kg IM or sub-Q to treat hypotension during spinal anesthesia.^b

Nasal Congestion

Oral

Self-medication in children 2–5 years of age: 2.5 mg every 4 hours.¹²⁴

Self-medication in children 6–11 years of age: 5 mg every 4 hours.¹²⁴

Self-medication in children ≥12 years of age: Usually, 10 mg every 4 hours.^{114 b}

May be administered in fixed combination with other drugs.^b

Discontinue therapy if symptoms persist for >7 days or are accompanied by fever or if nervousness, dizziness, or insomnia occurs.^{114 124}

Hemorrhoids

Temporary Relief

Topical or Rectal

Children ≥12 years of age: Self-medication with a cream, gel, ointment, or suppository containing 0.25% of the drug alone or in combination with other anorectal agents (e.g., protectants, local anesthetics, astringents, antipruritics, analgesics).^{101 102 103 104 105 106 107 108}

Administer at bedtime, in the morning, and after bowel movements^{102 103 104 105 106} up to 4 times daily.^{101 102 103 104 105 106 107 108}

Do not exceed the recommended dosage unless otherwise directed by a clinician.^{101 102 103 104 105 106 107 108}

Anorectal dosage for self-medication of hemorrhoids should not exceed 2 mg daily (i.e., 0.5 mg 4 times daily).¹⁰⁸

Adults

Administer the lowest effective dosage for the shortest possible time; when possible, small doses should be injected initially and subsequent doses determined by pressor response.^b

Hypotension

Mild or Moderate

IM or Sub-Q

Usually, 2–5 mg; doses range from 1–10 mg.^b

Initially, do not exceed 5 mg.^b

IV

Usually, 0.2 mg by slow IV injection; doses range from 0.1–0.5 mg.^b

Initial dose should not exceed 0.5 mg; doses may be given no more frequently than every 10–15 minutes.^b

Severe Hypotension or Shock

IV

Administer as a dilute solution.^b (See Parenteral Administration under Dosage and Administration.)

Usually administer at an initial rate of 0.1–0.18 mg/minute; after the BP stabilizes, 0.04–0.06 mg/minute is usually adequate.^b

Rate of infusion is adjusted to maintain the BP at the desired level.^b

To produce the desired pressor response, additional drug in increments of 10 mg or more may be added to the infusion solution and the rate of flow adjusted according to the response of the patient.^b

Hypotensive emergencies: May be given IV in an initial dose of 0.2 mg; any subsequent dose should not exceed the previous dose by 0.1–0.2 mg and a single dose should not exceed 0.5 mg.^b

Hypotension During Spinal Anesthesia

Prevention

IM or Sub-Q

Low spinal anesthesia: Usually, 2 mg.^b

High spinal anesthesia: 3 mg may be necessary.^b

Administer 3–4 minutes prior to the spinal anesthetic.^b

Prolongation of Spinal Anesthesia

IV

Usually, 2–5 mg are added to the anesthetic solution.^b

Vasoconstriction for Regional Anesthesia

IV

Optimally, the concentration of phenylephrine hydrochloride is 0.05 mg/mL (1:20,000).^b

Solutions may be prepared for regional anesthesia by adding 1 mg of phenylephrine hydrochloride to each 20 mL of local anesthetic solution.^b

Some pressor response can be expected when at least 2 mg is injected.^b

Paroxysmal Supraventricular Tachycardia

IV

Initially, administer rapidly (within 20–30 seconds) by direct IV injection with a dose not exceeding 0.5 mg; increase subsequent doses in increments of 0.1–0.2 mg, depending on the BP response of the patient. ^b

Do not raise SBP above 160 mm Hg.^b

Maximum single dose is 1 mg.^b

Nasal Congestion

Oral

Self-medication: Usually, 10 mg every 4 hours.^{114 b} May be administered in fixed combination with other drugs.^b

Discontinue therapy if symptoms persist for >7 days or are accompanied by fever or if nervousness, dizziness, or insomnia occurs.¹¹⁴

Hemorrhoids

Temporary Relief

Topical or Rectal

Self-medication as a cream, gel, ointment, or suppository containing 0.25% of the drug alone or in combination with other anorectal agents (e.g., protectants, local anesthetics, astringents, antipruritics, analgesics).^{101 102 103 104 105 106 107 108}

Administer at bedtime, in the morning, and after bowel movements^{102 103 104 105 106} up to 4 times daily.^{101 102 103 104 105 106 107 108}

Do not to exceed the recommended dosage unless otherwise directed by a clinician.^{101 102 103 104 105 106 107 108}

Anorectal dosage for self-medication of hemorrhoids should not exceed 2 mg daily (i.e., 0.5 mg 4 times daily).¹⁰⁸

Prescribing Limits

Pediatric Patients

Nasal Congestion

Oral

Self-medication in children 2–5 years of age: Maximum 15 mg in any 24-hour period.¹²⁴

Self-medication in children 6–11 years of age: Maximum 30 mg in any 24-hour period.¹²⁴

Self-medication in children ≥12 years of age: Maximum 60 mg in any 24-hour period.¹¹⁴

Hemorrhoids (Temporary Relief)

Topical or Rectal

Children ≥12 years of age: Anorectal dosage for self-medication of hemorrhoids should not exceed 2 mg daily (i.e., 0.5 mg 4 times daily).¹⁰⁸

Adults

Hypotension

Mild or Moderate

Sub-Q or IM

Initially, do not exceed 5 mg.^b

IV

Initial dose should not exceed 0.5 mg; repeat doses no more frequently than every 10–15 minutes.^b

Hypotension during Spinal Anesthesia (Prevention)

IM or Sub-Q

Hypotensive emergencies: May be given IV in an initial dose of 0.2 mg; any subsequent dose should not exceed the previous dose by 0.1–0.2 mg and a single dose should not exceed 0.5 mg.^b

Paroxysmal Supraventricular Tachycardia

IV

Maximum single dose is 1 mg.^b

Do not raise SBP above 160 mm Hg.^b

Nasal Congestion

Oral

Self-medication: Maximum 60 mg in any 24-hour period.¹¹⁴

Hemorrhoids (Temporary Relief)

Topical or Rectal

Anorectal dosage for self-medication of hemorrhoids should not exceed 2 mg daily (i.e., 0.5 mg 4 times daily).¹⁰⁸

Cautions for Phenylephrine Hydrochloride

Contraindications

• 
  

  Severe hypertension or ventricular tachycardia.^b

  
  


• 
  

  Peripheral or mesenteric vascular thrombosis, because ischemia may be increased and the area of infarction extended.^b

  
  


• 
  

  For use in fingers, toes, ears, nose, or genitalia in conjunction with local anesthetics.^b

  
  


• 
  

  Severe coronary disease or cardiovascular disease (including MI) in the view of some clinicians.^b

  
  


• 
  

  For self-medication of hemorrhoidal symptoms unless otherwise directed by a clinician: Cardiac disease, high BP, thyroid disease, diabetes mellitus, or difficulty in urination secondary to prostatic hyperplasia.^{101 102 103 104 105 106 107 108}

  
  


• 
  

  Known hypersensitivity to phenylephrine or to any ingredient in the respective formulation.^b

  
  

Warnings/Precautions

Warnings

Hypovolemia

Pressor therapy is not a substitute for replacement of blood, plasma, fluids, and/or electrolytes.^b

Correct blood volume depletion as fully as possible before administration.^b

May be used in an emergency as an adjunct to fluid volume replacement or as a temporary supportive measure to maintain coronary and cerebral artery perfusion until volume replacement therapy can be completed, but phenylephrine must not be used as sole therapy in hypovolemic patients.^b

Additional volume replacement also may be necessary during or after administration of epinephrine, especially if hypotension recurs.^b

Monitoring of central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia; in addition, monitoring of central venous or pulmonary arterial diastolic pressure is necessary to avoid overloading the cardiovascular system and precipitating CHF.^b

Severe vasoconstrictive effects may be most likely to occur in hypovolemic patients.^b

Hypoxia and Acidosis

Hypoxia and acidosis may reduce the effectiveness of phenylephrine and must be identified and corrected prior to or concurrently with administration of the drug.^b

Concomitant Diseases

Administer with extreme caution to geriatric or hyperthyroid patients or those with bradycardia, partial heart block, myocardial disease, or severe arteriosclerosis.^b

Administer parenterally with extreme caution if at all to hypertensive patients.^b

If administered to patients with acute pancreatitis or hepatitis, the drug may increase ischemia in the liver or pancreas.^b

Do not use for self-medication for nasal congestion in patients with thyroid disease, diabetes mellitus, hypertension, heart disease, or difficulty urinating because of prostatic hypertrophy without consulting a clinician.^{114 124}

MAO Inhibitors and Antihypertensive Agents

Avoid use for self-medication for nasal congestion if currently receiving or have recently received (i.e., within 2 weeks) an MAO inhibitor.^{114 124}

Consult a clinician before initiating self-medication with an anorectal preparation of the drug if they currently are receiving an antihypertensive agent or antidepressant (e.g., MAO inhibitor).^{101 102 103 104 105 106 107 108}

Sensitivity Reactions

Sulfite Reactions

Some formulations of phenylephrine hydrochloride injection contain sulfites which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.^b

Major Toxicities

Overdosage

Overdosage may cause hypertension, headache, seizures, cerebral hemorrhage, palpitation, paresthesia, or vomiting; headache may be a symptom of hypertension.^b

Hypertension may be relieved by administration of an α-adrenergic blocking agent (e.g., phentolamine).^b

General Precautions

Prolonged Administration

Prolonged administration of vasopressors has caused edema, hemorrhage, focal myocarditis, subpericardial hemorrhage, necrosis of the intestine, or hepatic and renal necrosis; these effects have generally occurred in patients with severe shock and it is not clear if the drug or the shock state itself was the cause.^b

Combination Preparations

When used in combination with other drugs (e.g., acetaminophen, chlorpheniramine, dextromethorphan, diphenhydramine, guaifenesin, pheniramine), consider the cautions, precautions, and contraindications associated with all ingredients in the formulation.^{133 134 135 136 137 138 139 b}

Prolonged use of the drug may result in plasma volume depletion which may result in perpetuation of the shock state or the recurrence of hypotension when phenylephrine is discontinued.^b

Systemic Effects

Injections may be followed by paresthesia in the extremities or a feeling of coolness in the skin.^b

Cardiac Effects

When ≥2 mg is injected during regional local anesthesia, a pressor response may occur.^b

Administration by rapid IV injection in the treatment of paroxysmal supraventricular tachycardia may result in overdosage with short paroxysms of ventricular tachycardia, ventricular extrasystoles, or a sensation of fullness in the head.^b

Can cause severe bradycardia and decreased cardiac output.^b

Decreased cardiac output may be especially harmful to elderly patients and/or those with initially poor cerebral or coronary circulation.^b

Reduced Vital Organ Blood Flow

Can cause severe peripheral and visceral vasoconstriction, reduced blood flow to vital organs, decreased renal perfusion, and probably reduced urine output and metabolic acidosis.

Extravasation

May cause necrosis or sloughing of tissue if extravasation occurs during IV administration or following sub-Q administration.^b

Anorectal Use

Based on observations with local use for nasal congestion, prolonged local use of excessive anorectal dosages of vasoconstrictors will likely lead to rebound vasodilation and congestion.¹⁰⁸

Less commonly, prolonged local use of excessive anorectal dosages of vasoconstrictors can lead to anxiety and paranoia.¹⁰⁸

Contact dermatitis has been reported following topical application of certain formulations of vasoconstrictors.¹⁰⁸

Possibility that topical anorectal application of vasoconstrictors if absorbed systemically in adequate amounts could interact with MAO inhibitors resulting in potentiated hypertensive effects should be considered.¹⁰⁸

For additional precautions associated with anorectal phenylephrine therapy, see Topical and Rectal Administration under Dosage and Administration.

Specific Populations

Pregnancy

Category C.¹³²

Administration in late pregnancy or labor may cause fetal anoxia and bradycardia by increasing contractility of the uterus and decreasing uterine blood flow.^{132 b}

If a vasopressor is used in conjunction with oxytocic drugs, the vasopressor effect is potentiated and may result in potentially serious adverse effects.^b (See Oxytocic Drugs under Interactions.)

Use during pregnancy only when clearly needed.^b Other pressors (e.g., ephedrine) usually preferred.¹³²

Lactation

Does not appear to be distributed to any great extent into breast milk.¹²¹ However, caution if used in nursing women.^b

Pediatric Use

Risk of overdosage and toxicity (including death) in children <2 years of age receiving OTC preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection.^{128 129} Limited evidence of efficacy for these preparations in this age group; appropriate dosages not established.¹²⁸ Therefore, FDA recommends not to use such preparations in children <2 years of age; safety and efficacy in older children currently under evaluation. Because children 2–3 years of age also are at increased risk of overdosage and toxicity, some manufacturers of oral nonprescription cough and cold preparations recently agreed to voluntarily revise the product labeling to state that such preparations should not be used in children <4 years of age. During the transition period, some preparations on pharmacy shelves will have the new recommendation (“do not use in children <4 years of age”), while others will have the previous recommendation (“do not use in children <2 years of age”). FDA recommends that parents and caregivers adhere to dosage instructions and warnings on the product labeling that accompanies the preparation and consult a clinician about any concerns.

Geriatric Use

Administer with extreme caution to geriatric patients.^b

Common Adverse Effects

Systemic use: May cause restlessness, anxiety, nervousness, weakness, dizziness, precordial pain or discomfort, tremor, respiratory distress, pallor or blanching of the skin, or a pilomotor response.^b

Anorectal use: In recommended dosages for local effect in anorectal disorders (e.g., hemorrhoids), adverse systemic effects of vasoconstrictors such as phenylephrine generally are minimal.¹⁰⁸

Interactions for Phenylephrine Hydrochloride

Specific Drugs

Drug	Interaction	Comments
α-Adrenergic blocking agents (phentolamine mesylate, phenothiazine)	Vasopressor response to phenylephrine is decreased by prior administration of an α-adrenergic blocking agentb
β-Adrenergic blocking agents	Cardiostimulating effects of phenylephrine are blocked by prior administration of β-adrenergic blocking drugsb
Anesthetics, general (cyclopropane or halogenated hydrocarbon)	Cyclopropane or halogenated hydrocarbon general anesthetics increase cardiac irritability, may sensitize the myocardium to phenylephrine, and may result in arrhythmiasb	Use only with extreme caution or not at all with these general anestheticsb
Antidepressants, tricyclic	May potentiate the vasopressor effects of phenylephrineb
Atropine	Blocks the reflex bradycardia caused by phenylephrine and enhances the pressor response to phenylephrineb
Digoxin	Possibility that digoxin can sensitize the myocardium to the effects of sympathomimetic drugs should be consideredb
Ergot alkaloids	Excessive rise in BP may occur if phenylephrine is administered to patients receiving a parenteral injection of an ergot alkaloid such as ergonovine maleate132 b
Guanethidine	May potentiate the vasopressor effects of phenylephrineb
MAO inhibitors	Cardiac and pressor effects of phenylephrine are potentiated by prior administration of MAO inhibitors because metabolism of phenylephrine is reducedb The potentiation is greater following oral administration of phenylephrine than after parenteral administration of the drug because reduction of the metabolism of phenylephrine in the intestine results in increased absorption of the drugb	Avoid oral administration of phenylephrine in patients receiving an MAO inhibitor. Parenteral administration of phenylephrine to these patients, if unavoidable, should be undertaken with extreme caution and initial doses should be small Patients should consult a clinician before initiating anorectal phenylephrine therapy if they are receiving an MAO inhibitorb
Oxytocic drugs	The pressor effect of phenylephrine is potentiated132 b	If phenylephrine is used during labor and delivery to correct hypotension or is added to a local anesthetic solution, the obstetrician should be cautioned that some oxytocic drugs may cause severe persistent hypertension and that rupture of a cerebral blood vessel may occur during the postpartum period132 b
Phenothiazines	Phenothiazines have some α-adrenergic blocking effects; therefore, prior administration of a phenothiazine may reduce the pressor effect and duration of action of phenylephrineb
Sympathomimetic agents (epinephrine)	Combination products containing phenylephrine and a bronchodilator sympathomimetic agent should not be used concomitantly with epinephrine or other sympathomimetic agents because tachycardia or other serious arrhythmias may occurb

Phenylephrine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Completely absorbed following oral administration; undergoes extensive first-pass metabolism in the intestinal wall.^{121 122}

Bioavailability following oral administration is approximately 38% relative to IV administration.^{121 122} Because of extensive first-pass metabolism, considerable interindividual and possibly intraindividual variation in oral bioavailability exists.¹²¹

Peak serum concentrations occur at 0.75–2 hours following oral administration of 1- or 7.8-mg dose.^{121 122}

Given parenterally to achieve cardiovascular effects.^b

Onset

IV administration: Pressor effect occurs almost immediately.^b

IM administration: Pressor effect occurs within 10–15 minutes.^b

Oral administration: Nasal decongestion may occur within 15 or 20 minutes.^b

Duration

IV administration: Pressor effect persists for 15–20 minutes.^b

IM administration: Pressor effect persists for 30 minutes to 1–2 hours.^b

Oral administration: Nasal decongestion may persist for 2–4 hours.^b

Distribution

Extent

Undergoes rapid distribution into peripheral tissues; may be stored in certain organ compartments.¹²¹ Pharmacologic effects are terminated at least partially by uptake into tissues.^b

Penetration into the brain appears to be minimal.¹²¹

Not known if phenylephrine crosses the placenta.¹³²

Does not appear to be distributed to any great extent into breast milk.¹²¹

Elimination

Metabolism

Undergoes extensive metabolism in the intestinal wall (first-pass) and in the liver.^{121 122}

Principal routes of metabolism involve sulfate conjugation (principally in the intestinal wall) and oxidative deamination (by the enzyme MAO); glucuronidation also occurs to a lesser extent.^{121 122}

Elimination Route

Excreted in urine (80–86%) mainly as metabolites; unchanged drug accounts for 2.6 or 16% of an oral or IV dose, respectively.^{121 122}

Half-life

2–3 hours following oral or IV administration.^{121 122}

Special Populations

Clinical data regarding effects of renal or hepatic impairment on phenylephrine pharmacokinetics are limited.¹²¹

Because of extensive first-pass metabolism in the intestinal wall, hepatic impairment unlikely to result in major changes following oral administration; however, phenylephrine pharmacokinetics may be substantially altered following IV administration.¹²¹

Stability

Storage

Oral

Strips, orally dissolving

20–25°C.¹²⁴

Tablets

15–25°C in a dry place.¹¹⁴

Parenteral

Injection

Tight, light-resistant containers.^b

Up to 30°C protected from light.^b

Solutions diluted in 5% dextrose injection are stable for at least 48 hours at pH 3.5–7.5.^b

Stable for at least 48 hours when diluted to 0.02 mg/mL with 5% sodium bicarbonate injection.^b

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Dextran 6% in dextrose 5%
Dextran 6% in sodium chloride 0.9%
Dextrose–Ringer’s injection combinations
Dextrose–Ringer’s injection, lactated, combinations
Dextrose–saline combinations
Dextrose 2.5, 5 or, 10% in water
Fructose 10% in sodium chloride 0.9%
Fructose 10% in water
Invert sugar 5 and 10% in sodium chloride 0.9%
Invert sugar 5 and 10% in water
Ionosol products
Ringer’s injection
Ringer’s injection, lactated
Sodium bicarbonate 5%
Sodium chloride 0.45 or 0.9%
Sodium lactate (1/6) M

Drug Compatibility

Admixture CompatibilityHID

Compatible
Chloramphenicol sodium succinate
Chloramphenicol sodium succinate with sodium bicarbonate
Dobutamine HCl
Lidocaine HCl
Potassium chloride
Sodium bicarbonate
Sodium bicarbonate with chloramphenicol sodium succinate

Y-site CompatibilityHID

Compatible
Alcohol 10% in dextrose 5%
Amiodarone HCl
Argatroban
Bivalirudin