Phenylephrine vasoconstriction

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Phenylephrine (Systemic)

Introduction

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

Class: alpha-Adrenergic Agonists 12:12.04; AU100 (VA)

Synonyms: Phenylephrine

Uses

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

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 alone114,124 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 movements102,103,104,105,106 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 movements102,103,104,105,106 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

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

Specific Drugs
Drug Interaction Comments α-Adrenergic blocking Vasopressor response to phenylephrine is decreased by agents (phentolamine prior administration of an α-adrenergic blocking agent mesylate, [b] phenothiazine) β-Adrenergic blocking Cardiostimulating effects of phenylephrine are blocked by agents prior administration of β-adrenergic blocking drugs [b] Anesthetics, general Cyclopropane or halogenated hydrocarbon general Use only with extreme caution or not at all (cyclopropane or anesthetics increase cardiac irritability, may with these general anesthetics [b] halogenated sensitize the myocardium to phenylephrine, and may hydrocarbon) result in arrhythmias [b] Antidepressants, May potentiate the vasopressor effects of phenylephrine tricyclic [b] Atropine Blocks the reflex bradycardia caused by phenylephrine and enhances the pressor response to phenylephrine [b] Digoxin Possibility that digoxin can sensitize the myocardium to the effects of sympathomimetic drugs should be considered [b] 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 maleate [132,b] Guanethidine May potentiate the vasopressor effects of phenylephrine [b] MAO inhibitors Cardiac and pressor effects of phenylephrine are Avoid oral administration of phenylephrine in potentiated by prior administration of MAO inhibitors patients receiving an MAO inhibitor. because metabolism of phenylephrine is reduced [b] Parenteral administration of phenylephrine to The potentiation is greater following oral administration these patients, if unavoidable, should be of phenylephrine than after parenteral administration undertaken with extreme caution and initial of the drug because reduction of the metabolism of doses should be small phenylephrine in the intestine results in increased Patients should consult a clinician before absorption of the drug [b] initiating anorectal phenylephrine therapy if they are receiving an MAO inhibitor [b] Oxytocic drugs The pressor effect of phenylephrine is potentiated [132, If phenylephrine is used during labor and b] 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 period [132,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 phenylephrine [b] Sympathomimetic agents Combination products containing phenylephrine and a (epinephrine) bronchodilator sympathomimetic agent should not be used concomitantly with epinephrine or other sympathomimetic agents because tachycardia or other serious arrhythmias may occur [b]

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 CompatibilityHID
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 Compatibility [HID]
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 Compatibility [HID]
Compatible Alcohol 10% in dextrose 5% Amiodarone HCl Argatroban Bivalirudin Etomidate Famotidine Fenoldopam mesylate Haloperidol lactate Hetastarch in lactated electrolyte injection (Hextend) Inamrinone lactate Levofloxacin Remifentanil HCl Vasopressin Zidovudine Incompatible Lansoprazole Thiopental sodium Variable Propofol

Actions

• Acts predominantly by a direct effect on α-adrenergic receptors; in therapeutic doses, the drug has no substantial stimulant effect on the β-adrenergic receptors of the heart (β1-adrenergic receptors) but substantial activation of these receptors may occur when larger doses are given.b
• Believed that α-adrenergic effects result from the inhibition of the production of cyclic adenosine-3´,5´-monophosphate (cAMP) by inhibition of the enzyme adenyl cyclase, whereas β-adrenergic effects result from stimulation of adenyl cyclase activity.b
• Does not stimulate β-adrenergic receptors of the bronchi or peripheral blood vessels (β2-adrenergic receptors).b
• Main effect of therapeutic doses of phenylephrine is vasoconstriction.b
• Constricts resistance and, to a lesser degree, capacitance blood vessels by its effects on α-adrenergic receptors.
• Total peripheral resistance is increased, resulting in increased SBP and DBP.b
• Venous return to the heart may be decreased; however, phenylephrine increases venous pressure slightly.b
• Blood flow to vital organs, skin, and probably skeletal muscle is reduced.b
• May reduce circulating plasma volume (especially with prolonged use) as a result of loss of fluid into the extracellular spaces caused by postcapillary vasoconstriction.b
• Constriction of renal blood vessels by phenylephrine decreases renal blood flow.b
• Local vasoconstriction and hemostasis also occur following topical application or infiltration of phenylephrine into tissues.b
• Following oral administration, constriction of blood vessels in the nasal mucosa may relieve nasal congestion.b
• Main effect on the heart is bradycardia, which results from increased vagal activity occurring as a reflex to increased arterial BP.b
• Bradycardia occurs after parenteral administration of usual therapeutic doses and may also result from overdosage via oral inhalation.b
• Attacks of paroxysmal atrial or nodal tachycardia may be ended by the decrease in sympathetic cardioaccelerator tone and increase in parasympathomimetic cardiodecelerator tone.b
• Constricts coronary blood vessels but increases coronary blood flow, probably as a result of increased systemic BP.b
• In therapeutic doses, causes little if any CNS stimulation but may cause nervousness, restlessness, anxiety, dizziness, and tremor in some patients, especially after overdosage.b
• As a result of its effects on α-adrenergic receptors, may cause contraction of the pregnant uterus and constriction of uterine blood vessels; however, the vasoconstrictor effect may be overcome by an increase in maternal BP.b

Advice to Patients

• Importance of advising patients not to exceed the recommended dosage unless otherwise directed by a clinician.101,102,103,104,105,106,107, 108
• Importance of informing patient to consult a clinician before using for self-medication of nasal congestion if they have been diagnosed with thyroid disease, diabetes mellitus, hypertension, heart disease, or difficulty urinating because of prostatic hypertrophy.114,124
• Importance of discontinuing self-medication of nasal congestion and consulting a clinician if symptoms persist >7 days or are accompanied by fever or if nervousness, dizziness, or insomnia develops during therapy.114,124
• Importance of informing patients not to exceed 2 mg daily (i.e., 0.5 mg 4 times daily) for the anorectal dosage for self-medication of hemorrhoids.108
• Importance of informing patients to consult a clinician if the anorectal condition worsens or does not improve within 7 days or if bleeding occurs.101,102,103,104,105,106,107
• Importance of informing patients that when a special applicator such as a pile pipe or other mechanical devise is used to administer the drug intrarectally, the applicator should be attached to the tube of drug and then the applicator should be lubricated well and gently inserted into the rectum;101,102,104 cleanse the applicator thoroughly after each use and store according to the manufacturer's instructions.104
• Importance of advising patients to not use and to consult a clinician promptly if introduction of the applicator or device into the rectum causes additional pain.101,102,104,107
• Importance of informing patients to remove wrapper from suppositories prior to insertion into the rectum.101,102,106,107
• Importance of informing 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
• Importance of informing patients to consult a clinician promptly for advice if minor bleeding is present since anorectal bleeding may be a sign of conditions ranging in seriousness from simple abrasions to cancer.108
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.131
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.131
• Importance of informing patients of other important precautionary information.131 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

In response to concerns regarding the safety and efficacy of cough/cold preparations in young children, many OTC cough/cold preparations specifically formulated for infants have been voluntarily withdrawn from the US market.130 Therefore, some of the preparations described below may no longer be commercially available in the US.

Phenylephrine Hydrochloride
Routes Dosage Forms Strengths Brand Names Manufacturer Oral Strips, 2.5 mg Triaminic® Thin Strips® Cold Novartis orally with Stuffy Nose dissolving 10 mg Sudafed PE® McNeil Tablets, 10 mg Sudafed PE® McNeil film-coated Parenteral Injection 10 mg/mL* Neo-Synephrine® Hydrochloride Hospira Phenylephrine Hydrochloride Injection Topical Cream 0.25% with Glycerin 14.4%, Preparation H® Wyeth Pramoxine Hydrochloride 1%, and White Petrolatum 15% Gel 0.25% with Witch Hazel 50% Preparation H® Wyeth Nasal Spray 0.5% Vicks® Sinex® Nasal Spray Procter & Gamble Vicks® Sinex® Ultra Fine Mist Procter & Gamble Ointment 0.25% with Mineral Oil 14%, Preparation H® Wyeth Petrolatum 71.9%, and Shark Liver Oil 3% Suppository 0.25% with Cocoa Butter 85.5% Preparation H® Wyeth and Shark Liver Oil 3% ----------------------------------------------------------------------------------------------------------
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Phenylephrine Hydrochloride Combinations
Routes Dosage Forms Strengths Brand Names Manufacturer Oral Capsules, 5 mg with Acetaminophen 325 mg Vicks® DayQuil® Sinus LiquiCaps Procter & (liquid- Gamble filled) 5 mg with Acetaminophen 325 mg and Vicks® DayQuil® Cold/Flu LiquiCaps Procter & Dextromethorphan Hydrobromide 10 mg Gamble Gelcaps 5 mg with Acetaminophen 325 mg Tylenol® Sinus Congestion & Pain McNeil Daytime 5 mg with Acetaminophen 325 mg and Tylenol®Cold Multi-Symptom Daytime McNeil Dextromethorphan Hydrobromide 10 mg Gelcaps, 5 mg with Acetaminophen 325 mg Tylenol® Sinus Congestion & Pain McNeil rapid Daytime release 5 mg with Acetaminophen 325 mg and Tylenol® Allergy Multi-Symptom McNeil Chlorpheniramine Maleate 2 mg 5 mg with Acetaminophen 325 mg and Tylenol® Cold Multi-Symptom McNeil Dextromethorphan Hydrobromide 10 mg Daytime For Solution 10 mg/packet with Acetaminophen 325 mg/ Theraflu® Cold & Sore Throat Novartis packet and Pheniramine Maleate 20 mg/ packet 10 mg/packet with Acetaminophen 650 mg/ Theraflu® Daytime Severe Cold Novartis packet 10 mg/packet with Acetaminophen 650 mg/ Theraflu® Flu & Sore Throat Novartis packet and Pheniramine Maleate 20 mg/ packet Theraflu® Nighttime Severe Cold Novartis 10 mg/packet with Dextromethorphan Theraflu® Cold & Cough Novartis Hydrobromide 20 mg/packet and Pheniramine Maleate 20 mg/packet Solution 5 mg/15 mL with Acetaminophen 325 mg/15 mL Theraflu® Daytime Warming Relief Novartis and Dextromethorphan Hydrobromide 10 mg/ Syrup 15 mL Tylenol® Cold Multi-Symptom McNeil Daytime Citrus Burst® Liquid Vicks® DayQuil® Cold/Flu Relief Procter & Gamble 5 mg/15 mL with Acetaminophen 325 mg/15 Tylenol® Cold Multi-Symptom Citrus McNeil mL, Dextromethorphan Hydrobromide 10 mg/ Burst® Liquid 15 mL, and Guaifenesin 200 mg/15 mL 5 mg/15 mL with Acetaminophen 325 mg/15 mL Theraflu® Flu & Sore Throat Relief Novartis and Diphenhydramine Hydrochloride 12.5 Syrup mg/15 mL Theraflu®Nighttime Warming Relief Novartis Syrup 2.5 mg/5 mL with Acetaminophen 160 mg/5 mL Children's Tylenol® Plus Cold McNeil and Chlorpheniramine Maleate 1 mg/5 mL 2.5 mg/5 mL with Acetaminophen 160 mg/5 mL Children's Tylenol® Plus Multi- McNeil and Chlorpheniramine Maleate 1 mg/5 mL, Symptom Cold and Dextromethorphan Hydrobromide 5 mg/ 5mL 2.5 mg/5 mL with Acetaminophen 160 mg/5 mL Children's Tylenol® Plus Cold & McNeil and Diphenhydramine Hydrochloride 12.5 Allergy mg/5 mL 2.5 mg/5 mL with Chlorpheniramine Maleate Triaminic® Cold & Allergy Novartis 1 mg/5 mL 2.5 mg/5 mL with Dextromethorphan Children's Sudafed PE® Cold & McNeil Hydrobromide 5 mg/5mL Cough Triaminic® Day Time Cold & Cough Novartis 2.5 mg/5mL with Diphenhydramine Triaminic® Night Time Cough & Cold Novartis Hydrochloride 6.25 mg/5 mL 2.5 mg/5 mL with Guaifenesin 50 mg/5mL Triaminic® Chest & Nasal Novartis Congestion 10 mg/15 mL with Dextromethorphan Vicks® Formula 44D Cough & Head Proctor & Hydrobromide 20 mg/15 mL Congestion Relief Gamble 5 mg/5 mL with Diphenhydramine Children's Benadryl-D® Allergy & Pfizer Hydrochloride 12.5 mg/5 mL Sinus Strips, 2.5 mg with Dextromethorphan 3.67 mg Day Time Triaminic® Thin Strips® Novartis orally (equivalent to Dextromethorphan Cold & Cough dissolving Hydrobromide 5 mg) 5 mg with Diphenhydramine Hydrochloride Night Time Triaminic® Thin Strips® Novartis 12.5 mg Cold & Cough 10 mg with Dextromethorphan 14.8 mg Theraflu® Thin Strips® Daytime Novartis (equivalent to Dextromethorphan Cold & Cough Hydrobromide 20 mg) 10 mg with Diphenhydramine Hydrochloride Theraflu® Thin Strips® Nighttime Novartis 25 mg Cold & Cough Tablets 5 mg with Acetaminophen 325 mg, Theraflu® Nighttime Severe Cold Novartis Chlorpheniramine Maleate 2 mg, and Caplets Dextromethorphan Hydrobromide 15 mg 5 mg with Acetaminophen 325 mg and Theraflu® Daytime Severe Cold Novartis Dextromethorphan Hydrobromide 15 mg Caplets 10 mg with Chlorpheniramine Maleate 4 mg Sudafed PE® Sinus & Allergy McNeil Tablets, 5 mg with Acetaminophen 325 mg Excedrin® Sinus Headache Novartis film- coated Sudafed PE® Sinus Headache Caplets McNeil Tylenol® Sinus Congestion & Pain McNeil Daytime Caplets 5 mg with Acetaminophen 325 mg and Tylenol® Allergy Multi-Symptom McNeil Chlorpheniramine Maleate 2 mg Cool Burst® Caplets Tylenol® Sinus Congestion & Pain McNeil Nighttime Caplets 5 mg with Acetaminophen 325 mg, Tylenol® Cold Multi-Symptom McNeil Chlorpheniramine Maleate 2 mg, and Nighttime Cool Burst® Caplets Dextromethorphan Hydrobromide 10 mg Tylenol® Cold Head Congestion McNeil Nighttime Cool Burst® Caplets 5 mg with Acetaminophen 325 mg and Tylenol® Cold Multi-Symptom McNeil Dextromethorphan Hydrobromide 10 mg Daytime Cool Burst® Caplets Tylenol® Cold Head Congestion McNeil Daytime Cool Burst® Caplets 5 mg with Acetaminophen 325 mg, Sudafed PE® Cold & Cough Caplets McNeil Dextromethorphan Hydrobromide 10 mg, and Guaifenesin 100 mg 5 mg with Acetaminophen 325 mg, Tylenol® Cold Multi-Symptom Severe McNeil Dextromethorphan Hydrobromide 10 mg, and Cool Burst® Caplets Guaifenesin 200 mg Tylenol® Cold Head Congestion McNeil Severe Cool Burst® Caplets 5 mg with Acetaminophen 325 mg and Benadryl® Allergy & Cold Caplets Pfizer Diphenhydramine Hydrochloride 12.5 mg Benadryl® Allergy & Sinus Headache Pfizer Caplets Sudafed PE® Multi-Symptom Severe McNeil Cold Caplets 5 mg with Acetaminophen 325 mg and Benadryl® Severe Allergy & Sinus Pfizer Diphenhydramine Hydrochloride 25 mg Headache Caplets Maximum Strength Sudafed PE® Nighttime Cold Caplets McNeil Tylenol® Allergy Multi-Symptom McNeil Nighttime Cool Burst® Caplets 5 mg with Acetaminophen 325 mg and Tylenol® Sinus Congestion & Pain McNeil Guaifenesin 200 mg Severe Caplets 5 mg with Guaifenesin 200 mg Sudafed PE® Non-Drying Sinus McNeil Caplets 10 mg with Diphenhydramine Hydrochloride Benadryl-D® Allergy & Sinus Pfizer 25 mg Sudafed PE® Nighttime Nasal McNeil Decongestant

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2010. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AlleRx 3-7.5MG/5ML Suspension (CORNERSTONE BIOPHARMA): 473/$206.28 or 1419/$573.13

Bromfed-PD 6-7.5MG 12-hr Capsules (VICTORY PHARMA): 30/$70.99 or 90/$192.98

Duraphen 1000 30-1000MG 12-hr Tablets (KOWA PHARMACEUTICALS AMERICA): 100/$99.99 or 300/$271.86

Duraphen Forte 30-30-1200MG 12-hr Tablets (KOWA PHARMACEUTICALS AMERICA): 100/$132.57 or 300/$375.84

Duraphen II DM 20-20-800MG 12-hr Tablets (KOWA PHARMACEUTICALS AMERICA): 30/$41.76 or 90/$125.02

Duratuss AC 12 15-12.5-15MG/5ML Suspension (VICTORY PHARMA): 473/$215.97 or 1419/$610.03

Duratuss GP 25-1200MG 12-hr Tablets (VICTORY PHARMA): 30/$59.99 or 90/$159.99

Guaphen Forte 30-30-1200MG 12-hr Tablets (RIVER'S EDGE PHARMACEUTICALS): 30/$31.52 or 90/$85.1

Promethazine VC Plain 6.25-5MG/5ML Syrup (QUALITEST): 473/$39.97 or 1419/$109.97

R-Tanna 9-25MG Tablets (PRASCO LABORATORIES): 30/$39.99 or 90/$102.97

Rynatan 9-25MG Tablets (MEDA PHARMACEUTICALS): 30/$109.98 or 90/$307.96

Rynatan Pediatric 4.5-5MG/5ML Suspension (MEDA PHARMACEUTICALS): 120/$87.11 or 360/$254.05

Sitrex 30-1200MG 12-hr Tablets (VINDEX PHARMACEUTICALS INC.): 30/$19.94 or 90/$58.76