[[hypotension]] resulting primarily from [[vasodilation]], in such settings as [[septic shock]] or [[anesthesia]]
|hasBlackBoxWarning=
|hasBlackBoxWarning=
Yes
|adverseReactions=
|adverseReactions=
[[nausea]] and [[vomiting]], [[headache]], nervousness
<!--Black Box Warning-->
<!--Black Box Warning-->
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|fdaLIADAdult=
*Phenylephrine Hydrochloride Injection is generally injected subcutaneously, intramuscularly, slowly intravenously or in dilute solution as a continuous intravenous infusion. In patients with paroxysmal supraventricular tachycardia and, if indicated, in case of emergency, Phenylephrine Hydrochloride Injection is administered directly intravenously. The dose should be adjusted according to the pressor response
=====Perioperative Hypotension=====
T1
*For convenience in intermittent intravenous administration, dilute 1 mL Phenylephrine Hydrochloride Injection 1% with 9 mL Sterile Water for Injection, USP, to yield 0.1% Phenylephrine Hydrochloride Injection.
T2
=====Mild or Moderate Hypotension=====
*SUBCUTANEOUSLY OR INTRAMUSCULARLY: Usual dose, from 2 mg to 5 mg. Range, from 1 mg to 10 mg. Initial dose should not exceed 5 mg.
*INTRAVENOUSLY: Usual dose, 0.2 mg. Range, from 0.1 mg to 0.5 mg. Initial dose should not exceed 0.5 mg.
*Injections should not be repeated more often than every 10 to 15 minutes. A 5 mg intramuscular dose should raise blood pressure for one to two hours. A 0.5 mg intravenous dose should elevate the blood pressure for about 15 minutes.
=====Severe Hypotension and Shock - Including Drug-Related Hypotension=====
*Blood volume depletion should always be corrected as fully as possible before any vasopressor is administered. When, as an emergency measure, intraaortic pressures must be maintained to prevent cerebral or coronary artery ischemia, phenylephrine can be administered before and concurrently with blood volume replacement.
*Hypotension and occasionally severe shock may result from overdosage or idiosyncrasy following the administration of certain drugs, especially adrenergic and ganglionic blocking agents, rauwolfia and veratrum alkaloids and phenothiazine tranquilizers. Patients who receive a phenothiazine derivative as preoperative medication are especially susceptible to these reactions. As an adjunct in the management of such episodes, Phenylephrine Hydrochloride Injection is a suitable agent for restoring blood pressure.
*Higher initial and maintenance doses of phenylephrine are required in patients with persistent or untreated severe hypotension or shock. Hypotension produced by powerful peripheral adrenergic blocking agents, chlorpromazine or pheochromocytomectomy may also require more intensive therapy.
*Continuous Infusion:
:*Add 10 mg of the drug (1 mL of 1 percent solution) to 500 mL of Dextrose Injection, USP or Sodium Chloride Injection, USP (providing a 1:50,000 solution). To raise the blood pressure rapidly, start the infusion at about 100 mcg to 180 mcg per minute (based on 20 drops per mL this would be 100 to 180 drops per minute). When the blood pressure is stabilized (at a low normal level for the individual), a maintenance rate of 40 mcg to 60 mcg per minute usually suffices (based on 20 drops per mL this would be 40 to 60 drops per minute). If the drop size of the infusion system varies from the 20 drops per mL the dose must be adjusted accordingly.
:*If a prompt initial pressor response is not obtained, additional increments of phenylephrine (10 mg or more) are added to the infusion bottle. The rate of flow is then adjusted until the desired blood pressure level is obtained. (In some cases, a more potent vasopressor, such as norepinephrine bitartrate, may be required.) Hypertension should be avoided. The blood pressure should be checked frequently. Headache and/or bradycardia may indicate hypertension. Arrhythmias are rare.
===== Spinal Anesthesia-Hypotension =====
*Routine parenteral use of phenylephrine has been recommended for the prophylaxis and treatment of hypotension during spinal anesthesia. It is best administered subcutaneously or intramuscularly three or four minutes before injection of the spinal anesthetic. The total requirement for high anesthetic levels is usually 3 mg, and for lower levels, 2 mg. For hypotensive emergencies during spinal anesthesia, phenylephrine may be injected intravenously, using an initial dose of 0.2 mg. Any subsequent dose should not exceed the previous dose by more than 0.1 mg to 0.2 mg and no more than 0.5 mg should be administered in a single dose.
*In adult patients undergoing surgical procedures with either neuraxial anesthesia or general anesthesia:
:*50 mcg to 250 mcg by intravenous bolus administration. The most frequently reported initial bolus dose is 50 mcg or 100 mcg.
:*0.5 mcg/kg/min to 1.4 mcg/kg/min by intravenous continuous infusion, titrated to blood pressure goal.
*To combat hypotension during spinal anesthesia in children, a dose of 0.5 mg to 1 mg per 25 pounds body weight, administered subcutaneously or intramuscularly, is recommended.
=====Septic or Other Vasodilatory Shock=====
===== Prolongation of Spinal Anesthesia =====
*No bolus.
*The addition of 2 mg to 5 mg of phenylephrine hydrochloride to the anesthetic solution increases the duration of motor block by as much as approximately 50 percent without any increase in the incidence of complications such as nausea, vomiting or blood pressure disturbances.
*0.5 mcg/kg/min to 6 mcg/kg/min by intravenous continuous infusion, titrated to blood pressure goal. Doses above 6 mcg/kg/min do not show significant incremental increase in blood pressure.
=====Vasoconstrictor for Regional Analgesia=====
*Concentrations about ten times those employed when epinephrine is used as a vasoconstrictor are recommended. The optimum strength is 1:20,000 (made by adding 1 mg of phenylephrine hydrochloride to every 20 mL of local anesthetic solution). Some pressor responses can be expected when 2 mg or more are injected.
=====Paroxysmal Supraventricular Tachycardia=====
*Rapid intravenous injection (within 20 to 30 seconds) is recommended. The initial dose should not exceed 0.5 mg, and subsequent doses, which are determined by the initial blood pressure response, should not exceed the preceding dose by more than 0.1 mg to 0.2 mg and should never exceed 1 mg.
*Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
=====Vasoconstriction and Pupil Dilation=====
*Phenylephrine Hydrochloride Ophthalmic Solution, 2.5% is especially useful when rapid and powerful dilation of the pupil without cycloplegia and reduction of congestion in the capillary bed are desired. A drop of a suitable topical anesthetic may be applied, followed in a few minutes by 1 drop of Phenylephrine Hydrochloride Ophthalmic Solution, 2.5% on the upper limbus. The anesthetic prevents stinging and consequent dilution of the solution by lacrimination. It may occasionally be necessary to repeat the instillation after one hour, again preceded by the use of the topical anesthetic.
=====Uveitis=====
=====Uveitis=====
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* Phenylephrine Hydrochloride Injection should not be used in patients with severe hypertension, ventricular tachycardia or in patients who are hypersensitive to it or to any of the components.
* Phenylephrine Hydrochloride Injection should not be used in patients with severe hypertension, ventricular tachycardia or in patients who are hypersensitive to it or to any of the components.
*Ophthalmic solutions of phenylephrine HCl are contraindicated in patients with anatomically narrow angles or narrow angle glaucoma. Phenylephrine HCl may be contraindicated in low birth weight infants and in some elderly adults with severe arteriosclerotic cardiovascular or cerebrovascular disease. Phenylephrine HCl may be contraindicated during intraocular operative procedures when the corneal epithelial barrier has been disturbed. This preparation is also contraindicated in persons with a known sensitivity to phenylephrine HCl or any of its components.
<!--Warnings-->
<!--Warnings-->
|warnings=
|warnings=
*If used in conjunction with oxytocic drugs, the pressor effect of sympathomimetic pressor amines is potentiated (see PRECAUTIONS, Drug Interactions). The obstetrician should be warned that some oxytocic drugs may cause severe persistent hypertension and that even a rupture of a cerebral blood vessel may occur during the postpartum period.
*This product contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
====Precautions====
====Precautions====
* Phenylephrine hydrochloride should be employed only with extreme caution in elderly patients or in patients with hyperthyroidism, bradycardia, partial heart block, myocardial disease or severe arteriosclerosis.
*Exacerbation of Angina, Heart Failure, or Pulmonary Arterial Hypertension
:*Because of its pressor effects, phenylephrine hydrochloride can precipitate angina in patients with severe arteriosclerosis or history of angina, exacerbate underlying heart failure, and increase pulmonary arterial pressure.
<!--Adverse Reactions-->
*Bradycardia
:*Phenylephrine hydrochloride can cause severe bradycardia and decreased cardiac output.
<!--Clinical Trials Experience-->
*Risk in Patients with Autonomic Dysfunction
:*The pressor response to adrenergic drugs, including phenylephrine, can be increased in patients with autonomic dysfunction, as may occur with spinal cord injuries.
|clinicalTrials=
*Skin and Subcutaneous Necrosis
:*Extravasation of phenylephrine can cause necrosis or sloughing of tissue.
*Headache, reflex bradycardia, excitability, restlessness and rarely arrhythmias.
*Pressor Effect with Concomitant Oxytocic Drugs
:*Oxytocic drugs potentiate the pressor effect of sympathomimetic pressor amines including phenylephrine hydrochloride [see Drug Interactions (7.1)], with the potential for hemorrhagic stroke.
=====Body as a Whole=====
*Allergic Reactions
:*This product contains sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
*Peripheral and Visceral Ischemia
:*Phenylephrine hydrochloride can cause excessive peripheral and visceral vasoconstriction and ischemia to vital organs, particularly in patients with extensive peripheral vascular disease.
*Renal Toxicity
:*Phenylephrine hydrochloride can increase the need for renal replacement therapy in patients with septic shock. Monitor renal function.
<!--Adverse Reactions-->
=====Cardiovascular=====
<!--Clinical Trials Experience-->
|clinicalTrials=
*The following adverse reactions associated with the use of phenylephrine hydrochloride were identified in the literature. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.
=====Cardiac disorders=====
=====Digestive=====
Bradycardia, AV block, ventricular extrasystoles, myocardial ischemia
=====Gastrointestinal disorders=====
Nausea, vomiting
=====General disorders and administrative site conditions=====
=====Endocrine=====
Chest pain, extravasation
=====Immune system disorders=====
Sulfite sensitivity
=====Nervous system disorders=====
=====Hematologic and Lymphatic=====
Headache, nervousness, paresthesia, tremor
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Psychiatric disorders=====
Excitability
=====Respiratory=====
=====Respiratory=====
Pulmonary edema, rales
=====Skin and subcutaneous tissue disorders=====
Diaphoresis, pallor, piloerection, skin blanching, skin necrosis with extravasation
=====Skin and Hypersensitivy Reactions=====
=====Vascular disorders=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
Hypertensive crisis
<!--Postmarketing Experience-->
<!--Postmarketing Experience-->
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There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Drug Interactions-->
<!--Drug Interactions-->
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|drugInteractions=
|drugInteractions=
* MAO Inhibitors
* Agonists
:*The pressor effect of sympathomimetic pressor amines is markedly potentiated in patients receiving monoamine oxidase inhibitors (MAOI). Therefore, when initiating pressor therapy in these patients, the initial dose should be small and used with due caution. The pressor response of adrenergic agents may also be potentiated by tricyclic antidepressants.
:*The pressor effect of phenylephrine hydrochloride is increased in patients receiving:
:**Monoamine oxidase inhibitors (MAOI), such as selegiline.
:**β-adrenergic blockers
:**α-2 adrenergic agonists, such as clonidine
:**Steroids
:**Tricyclic antidepressants
:**Norepinephrine transport inhibitors, such as atomoxetine
:**Ergot alkaloids, such as methylergonovine maleate
:**Centrally-acting sympatholytic agents, such as guanfacine or reserpine
:**Atropine sulfate
*Antagonists
:*α-adrenergic blocking agents, including phenothiazines (e.g., chlorpromazine) and amiodarone block phenylephrine and are in turn blocked by phenylephrine.
<!--Use in Specific Populations-->
<!--Use in Specific Populations-->
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|useInRenalImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
*In patients with end stage renal disease (ESRD) undergoing hemodialysis, dose-response data indicates increased responsiveness to phenylephrine. Consider using lower doses of phenylephrine hydrochloride in ESRD patients.
|useInHepaticImpair=
|useInHepaticImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
*In patients with liver cirrhosis [Child Pugh Class A (n=3), Class B (n=5) and Class C (n=1)], dose-response data indicate decreased responsiveness to phenylephrine. Consider using larger doses than usual in hepatic impaired subjects.
|useInReproPotential=
|useInReproPotential=
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|PK=
|PK=
There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
*Following an intravenous infusion of phenylephrine hydrochloride, the effective half-life was approximately 5 minutes. The steady-state volume of distribution (340 L) exceeded the body volume by a factor of 5, suggesting a high distribution into certain organ compartments. The average total serum clearance (2095 mL/min) was close to one-third of the cardiac output.
*A mass balance study showed that phenylephrine is extensively metabolized by the liver with only 12% of the dose excreted unchanged in the urine. Deamination by monoamino oxidase is the primary metabolic pathway resulting in the formation of the major metabolite (m-hydroxymandelic acid) which accounts for 57% of the total administered dose.
<!--Nonclinical Toxicology-->
<!--Nonclinical Toxicology-->
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|clinicalStudies=
|clinicalStudies=
There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
*Increases in systolic and mean blood pressure following administration of phenylephrine were observed in 42 literature-based studies in the perioperative setting, including 26 studies where phenylephrine was used in low-risk (ASA 1 and 2) pregnant women undergoing neuraxial anesthesia during cesarean delivery, 3 studies in non-obstetric surgery under neuraxial anesthesia, and 13 studies in patients undergoing surgery under general anesthesia. Mean arterial blood pressure increases were also observed in two double-blind, active-controlled studies in patients with septic shock.
<!--How Supplied-->
<!--How Supplied-->
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|howSupplied=
*Phenylephrine Hydrochloride Injection, USP 1% (10 mg/mL) is supplied as follows:
*Phenylephrine Hydrochloride Injection, USP, is supplied as follows:
:*NDC 0641-6088-25
:*NDC 0641-6142-25: 1 mL single dose vials packaged in cartons containing 25 vials per carton.
:*1 mL Single Dose vial packaged in 25s
*Store at 20°-25°C (68°-77°F), excursions permitted to 15°-30°C (59°-86°F). PROTECT FROM LIGHT. Keep covered in carton until time of use. FOR SINGLE USE ONLY. DISCARD UNUSED PORTION.
*Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Keep covered in carton until time of use. For single use only. Discard unused portion.
*Phenylephrine Hydrochloride Ophthalmic Solution, 2.5% in plastic DROP-TAINER* dispensers:
:*3mL NDC 61314-342-01
:*5mL NDC 61314-342-02
<!--Patient Counseling Information-->
<!--Patient Counseling Information-->
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|fdaPatientInfo=
|fdaPatientInfo=
There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
*Inform patients, families, or caregivers that the primary side effect of phenylephrine is hypertension and rarely, hypertensive crisis. Patients may experience bradycardia (slow heart rate), which in some cases may produce heart block or other cardiac arrhythmias, extra ventricular beats, myocardial ischemia in patients with underlying cardiac disease, and pulmonary edema (fluid in the lungs) or rales. Common, less serious symptoms include the following:
:*Chest pain
:*Skin or tissue damage if the drug leaks out of the venous catheter into the surrounding tissue
:*Headache, nervousness, tremor, numbness/tingling (paresthesias) in hands or feet
:*Nausea, vomiting
:*Excitability, dizziness, sweating, flushing
<!--Precautions with Alcohol-->
<!--Precautions with Alcohol-->
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|brandNames=
|brandNames=
* PHENYLEPHRINE HYDROCHLORIDE ®<ref>{{Cite web | title = PHENYLEPHRINE HYDROCHLORIDE phenylephrine hydrochloride injection | url = dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7dfaac8d-ceab-4af0-9c44-bed73414789d }}</ref>
* PHENYLEPHRINE HYDROCHLORIDE ®<ref>{{Cite web | title = PHENYLEPHRINE HYDROCHLORIDE phenylephrine hydrochloride injection | url = http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e1a7ab4b-0afe-4463-a039-5be0323cf2f7 }}</ref>
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
In adult patients undergoing surgical procedures with either neuraxial anesthesia or general anesthesia:
50 mcg to 250 mcg by intravenous bolus administration. The most frequently reported initial bolus dose is 50 mcg or 100 mcg.
0.5 mcg/kg/min to 1.4 mcg/kg/min by intravenous continuous infusion, titrated to blood pressure goal.
Septic or Other Vasodilatory Shock
No bolus.
0.5 mcg/kg/min to 6 mcg/kg/min by intravenous continuous infusion, titrated to blood pressure goal. Doses above 6 mcg/kg/min do not show significant incremental increase in blood pressure.
Uveitis
Posterior Synechiae: Phenylephrine Hydrochloride Ophthalmic Solution, 2.5% may be used in patients with uveitis when synechiae are present or may develop. The formation of synechiae may be prevented by the use of this solution and atropine or other cycloplegics to produce wide dilation of the pupil. For recently formed posterior synechiae one drop of Phenylephrine Hydrochloride Ophthalmic Solution, 2.5% may be applied to the upper surface of the cornea and be repeated as necessary, not to exceed three times. Treatment may be continued the following day, if necessary. Atropine sulfate and the application of hot compresses should also be used if indicated.
Glaucoma
Phenylephrine Hydrochloride Ophthalmic Solution, 2.5% may be used with miotics in patients with open angle glaucoma. It reduces the difficulties experienced by the patient because of the small field produced by miosis, and still it permits and often supports the effect of the miotic in lowering the intraocular pressure in open angle glaucoma. Hence, there may be marked improvement in visual acuity after using Phenylephrine Hydrochloride Ophthalmic Solution, 2.5% in conjunction with miotic drugs.
Surgery
When a short-acting mydriatic is needed for wide dilation of the pupil before intraocular surgery, Phenylephrine Hydrochloride Ophthalmic Solution, 2.5% may be applied topically from 30 to 60 minutes before the operation.
Refraction
Phenylephrine Hydrochloride Ophthalmic Solution, 2.5% may be used effectively to increase mydriasis with homatropine hydrobromide, cyclopentolate hydrochloride, tropicamide hydrochloride and atropine sulfate.
One drop of the preferred cycloplegic is placed in each eye, followed in 5 minutes by one drop of Phenylephrine Hydrochloride Ophthalmic Solution, 2.5%. Since adequate cycloplegia is achieved at different time intervals after the instillation of the necessary number of drops, different cycloplegics will require different waiting periods to achieve adequate cycloplegia.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Phenylephrine (injection) in adult patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Phenylephrine (injection) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Phenylephrine (injection) in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Phenylephrine (injection) in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Phenylephrine (injection) in pediatric patients.
Contraindications
Phenylephrine Hydrochloride Injection should not be used in patients with severe hypertension, ventricular tachycardia or in patients who are hypersensitive to it or to any of the components.
Warnings
Precautions
Exacerbation of Angina, Heart Failure, or Pulmonary Arterial Hypertension
Because of its pressor effects, phenylephrine hydrochloride can precipitate angina in patients with severe arteriosclerosis or history of angina, exacerbate underlying heart failure, and increase pulmonary arterial pressure.
Bradycardia
Phenylephrine hydrochloride can cause severe bradycardia and decreased cardiac output.
Risk in Patients with Autonomic Dysfunction
The pressor response to adrenergic drugs, including phenylephrine, can be increased in patients with autonomic dysfunction, as may occur with spinal cord injuries.
Skin and Subcutaneous Necrosis
Extravasation of phenylephrine can cause necrosis or sloughing of tissue.
Pressor Effect with Concomitant Oxytocic Drugs
Oxytocic drugs potentiate the pressor effect of sympathomimetic pressor amines including phenylephrine hydrochloride [see Drug Interactions (7.1)], with the potential for hemorrhagic stroke.
Allergic Reactions
This product contains sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Peripheral and Visceral Ischemia
Phenylephrine hydrochloride can cause excessive peripheral and visceral vasoconstriction and ischemia to vital organs, particularly in patients with extensive peripheral vascular disease.
Renal Toxicity
Phenylephrine hydrochloride can increase the need for renal replacement therapy in patients with septic shock. Monitor renal function.
Adverse Reactions
Clinical Trials Experience
The following adverse reactions associated with the use of phenylephrine hydrochloride were identified in the literature. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.
Cardiac disorders
Bradycardia, AV block, ventricular extrasystoles, myocardial ischemia
Gastrointestinal disorders
Nausea, vomiting
General disorders and administrative site conditions
Chest pain, extravasation
Immune system disorders
Sulfite sensitivity
Nervous system disorders
Headache, nervousness, paresthesia, tremor
Psychiatric disorders
Excitability
Respiratory
Pulmonary edema, rales
Skin and subcutaneous tissue disorders
Diaphoresis, pallor, piloerection, skin blanching, skin necrosis with extravasation
Vascular disorders
Hypertensive crisis
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Phenylephrine (injection) in the drug label.
Drug Interactions
Agonists
The pressor effect of phenylephrine hydrochloride is increased in patients receiving:
Monoamine oxidase inhibitors (MAOI), such as selegiline.
β-adrenergic blockers
α-2 adrenergic agonists, such as clonidine
Steroids
Tricyclic antidepressants
Norepinephrine transport inhibitors, such as atomoxetine
Ergot alkaloids, such as methylergonovine maleate
Centrally-acting sympatholytic agents, such as guanfacine or reserpine
Atropine sulfate
Antagonists
α-adrenergic blocking agents, including phenothiazines (e.g., chlorpromazine) and amiodarone block phenylephrine and are in turn blocked by phenylephrine.
Animal reproduction studies have not been conducted with phenylephrine. It is also not known whether phenylephrine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Phenylephrine should be given to a pregnant woman only if clearly needed.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Phenylephrine (injection) in women who are pregnant.
Labor and Delivery
If vasopressor drugs are either used to correct hypotension or added to the local anesthetic solution, the obstetrician should be cautioned that some oxytocic drugs may cause severe persistent hypertension and that even a rupture of a cerebral blood vessel may occur during the postpartum period.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when phenylephrine hydrochloride is administered to a nursing woman.
Pediatric Use
To combat hypotension during spinal anesthesia in children, a dose of 0.5 mg to 1 mg per 25 pounds of body weight, administered subcutaneously or intramuscularly, is recommended.
Geriatic Use
There is no FDA guidance on the use of Phenylephrine (injection) with respect to geriatric patients.
Gender
There is no FDA guidance on the use of Phenylephrine (injection) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Phenylephrine (injection) with respect to specific racial populations.
Renal Impairment
In patients with end stage renal disease (ESRD) undergoing hemodialysis, dose-response data indicates increased responsiveness to phenylephrine. Consider using lower doses of phenylephrine hydrochloride in ESRD patients.
Hepatic Impairment
In patients with liver cirrhosis [Child Pugh Class A (n=3), Class B (n=5) and Class C (n=1)], dose-response data indicate decreased responsiveness to phenylephrine. Consider using larger doses than usual in hepatic impaired subjects.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Phenylephrine (injection) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Phenylephrine (injection) in patients who are immunocompromised.
Administration and Monitoring
Administration
Oral
Intravenous
Intramuscular
Subcutaneous
Monitoring
There is limited information regarding Monitoring of Phenylephrine (injection) in the drug label.
IV Compatibility
There is limited information regarding IV Compatibility of Phenylephrine (injection) in the drug label.
Overdosage
Acute Overdose
Signs and Symptoms
Overdosage may induce ventricular extrasystole and short paroxysms of ventricular tachycardia, a sensation of fullness in the head and tingling of the extremities.
The oral LD50 in the rat is 350 mg/kg, in the mouse 120 mg/kg.
Management
Should an excessive elevation of blood pressure occur, it may be immediately relieved by an α-adrenergic blocking agent (e.g. phentolamine).
Chronic Overdose
There is limited information regarding Chronic Overdose of Phenylephrine (injection) in the drug label.
Phenylephrine hydrochloride produces vasoconstriction that lasts longer than that of epinephrine and ephedrine. Responses are more sustained than those to epinephrine, lasting 20 minutes after intravenous and as long as 50 minutes after subcutaneous injection. Its action on the heart contrasts sharply with that of epinephrine and ephedrine, in that it slows the heart rate and increases the stroke output, producing no disturbance in the rhythm of the pulse.
Phenylephrine is a powerful postsynaptic alpha-receptor stimulant with little effect on the beta receptors of the heart. In therapeutic doses, it produces little if any stimulation of either the spinal cord or cerebrum. A singular advantage of this drug is the fact that repeated injections produce comparable effects.
Structure
Phenylephrine hydrochloride is a vasoconstrictor and pressor drug chemically related to epinephrine and ephedrine. Phenylephrine hydrochloride is a synthetic sympathomimetic agent in sterile form for parenteral injection. Chemically, phenylephrine hydrochloride is (-)-m-Hydroxy-α-[(methylamino)methyl]benzyl alcohol hydrochloride, and has the following structural formula:
Each mL contains: Phenylephrine Hydrochloride 10 mg; Sodium Chloride 3.5 mg; Sodium Citrate Dihydrate 4 mg; Citric Acid Monohydrate 1 mg; Sodium Metabisulfite 2 mg; Water for Injection q.s. pH adjusted with Sodium Hydroxide and/or Hydrochloric Acid if necessary. pH 3.0-6.5.
Pharmacodynamics
The predominant actions of phenylephrine are on the cardiovascular system. Parenteral administration causes a rise in systolic and diastolic pressures in man and other species. Accompanying the pressor response to phenylephrine is a marked reflex bradycardia that can be blocked by atropine; after atropine, large doses of the drug increase the heart rate only slightly. In man, cardiac output is slightly decreased and peripheral resistance is considerably increased. Circulation time is slightly prolonged, and venous pressure is slightly increased; venous constriction is not marked. Most vascular beds are constricted; renal splanchnic, cutaneous and limb blood flows are reduced but coronary blood flow is increased. Pulmonary vessels are constricted, and pulmonary arterial pressure is raised.
The drug is a powerful vasoconstrictor with properties very similar to those of norepinephrine but almost completely lacking the chronotropic and inotropic actions on the heart. Cardiac irregularities are seen only very rarely even with large doses.
Pharmacokinetics
Following an intravenous infusion of phenylephrine hydrochloride, the effective half-life was approximately 5 minutes. The steady-state volume of distribution (340 L) exceeded the body volume by a factor of 5, suggesting a high distribution into certain organ compartments. The average total serum clearance (2095 mL/min) was close to one-third of the cardiac output.
A mass balance study showed that phenylephrine is extensively metabolized by the liver with only 12% of the dose excreted unchanged in the urine. Deamination by monoamino oxidase is the primary metabolic pathway resulting in the formation of the major metabolite (m-hydroxymandelic acid) which accounts for 57% of the total administered dose.
Nonclinical Toxicology
No long-term animal studies have been done to evaluate the potential of phenylephrine in these areas.
Clinical Studies
Increases in systolic and mean blood pressure following administration of phenylephrine were observed in 42 literature-based studies in the perioperative setting, including 26 studies where phenylephrine was used in low-risk (ASA 1 and 2) pregnant women undergoing neuraxial anesthesia during cesarean delivery, 3 studies in non-obstetric surgery under neuraxial anesthesia, and 13 studies in patients undergoing surgery under general anesthesia. Mean arterial blood pressure increases were also observed in two double-blind, active-controlled studies in patients with septic shock.
How Supplied
Phenylephrine Hydrochloride Injection, USP, is supplied as follows:
NDC 0641-6142-25: 1 mL single dose vials packaged in cartons containing 25 vials per carton.
Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Keep covered in carton until time of use. For single use only. Discard unused portion.
Storage
There is limited information regarding Phenylephrine (injection) Storage in the drug label.
Images
Drug Images
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Inform patients, families, or caregivers that the primary side effect of phenylephrine is hypertension and rarely, hypertensive crisis. Patients may experience bradycardia (slow heart rate), which in some cases may produce heart block or other cardiac arrhythmias, extra ventricular beats, myocardial ischemia in patients with underlying cardiac disease, and pulmonary edema (fluid in the lungs) or rales. Common, less serious symptoms include the following:
Chest pain
Skin or tissue damage if the drug leaks out of the venous catheter into the surrounding tissue
Headache, nervousness, tremor, numbness/tingling (paresthesias) in hands or feet
Nausea, vomiting
Excitability, dizziness, sweating, flushing
Precautions with Alcohol
Alcohol-Phenylephrine (injection) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
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