Product Elements:
Phenylephrine hydrochloride phenylephrine hydrochloride phenylephrine hydrochloride phenylephrine sodium chloride trisodium citrate dihydrate citric acid monohydrate sodium metabisulfite water sodium hydroxide hydrochloric acid phenylephrine hydrochloride phenylephrine hydrochloride phenylephrine hydrochloride phenylephrine sodium chloride citric acid monohydrate trisodium citrate dihydrate water sodium metabisulfite sodium hydroxide hydrochloric acid
Drug Interactions:
7 drug interactions agonistic effects with monoamine oxidase inhibitors (maoi), β-adrenergic blocking agents, α-2 adrenergic agonists, steroids, tricyclic antidepressants, norepinephrine transport inhibitors, ergot alkaloids, centrally-acting sympatholytic agents and atropine sulfate ( 7.1 ) antagonistic effects on and by α-adrenergic blocking agents ( 7.2 ) 7.1 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 7.2 antagonists α-adrenergic blocking agents, including phenothiazines (e.g., chlorpromazine) and amiodarone block phenylephrine and are in turn blocked by phenylephrine.
Read more... Indications and Usage:
1 indications and usage phenylephrine hydrochloride is an alpha-1 adrenergic receptor agonist indicated for increasing blood pressure in adults with clinically important hypotension resulting primarily from vasodilation, in such settings as septic shock or anesthesia. phenylephrine hydrochloride is an alpha-1 adrenergic receptor agonist indicated for increasing blood pressure in adults with clinically important hypotension resulting primarily from vasodilation, in such settings as septic shock or anesthesia.
Warnings and Cautions:
5 warnings and precautions severe bradycardia and decreased cardiac output: ( 5.2 ) extravasation: during intravenous administration may cause necrosis or sloughing of tissue ( 5.4 ) concomitant use with oxytocic drugs: pressor effect of sympathomimetic pressor amines is potentiated ( 5.5 ) allergic-type reactions: sulfite ( 5.6 ) 5.1 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. 5.2 bradycardia phenylephrine hydrochloride can cause severe bradycardia and decreased cardiac output. 5.3 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. 5.4 skin and subcutaneous necrosis extravasation
Read more...of phenylephrine can cause necrosis or sloughing of tissue. 5.5 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. 5.6 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. 5.7 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. 5.8 renal toxicity phenylephrine hydrochloride can increase the need for renal replacement therapy in patients with septic shock. monitor renal function.
Dosage and Administration:
2 dosage and administration dilute before administration. ( 2.1 ) dosing for perioperative hypotension ⢠intravenous bolus administration: 50 mcg to 250 mcg ( 2.4 ) ⢠intravenous continuous infusion: 0.5 mcg/kg/minute to 1.4 mcg/kg/minute titrated to effect ( 2.4 ) dosing for patients with vasodilatory shock ⢠intravenous continuous infusion: 0.5 mcg/kg/minute to 6 mcg/kg/minute titrated to effect ( 2.5 ) 2.1 general administration instructions phenylephrine hydrochloride must be diluted before administration as bolus intravenous infusion or continuous intravenous infusion. inspect the solution for particulate matter and discoloration prior to administration. the diluted solution should not be held for more than 4 hours at room temperature or for more than 24 hours under refrigerated conditions. discard any unused portion. during phenylephrine hydrochloride administration: correct intravascular volume depletion. correct acidosis. acidosis may reduce the effectiveness of
Read more...phenylephrine. 2.2 preparing a 100 mcg/ml solution for bolus intravenous administration for bolus intravenous administration, withdraw 10 mg (1 ml of a 10 mg/ml concentration) of phenylephrine hydrochloride injection and dilute with 99 ml of 5% dextrose injection, usp or 0.9% sodium chloride injection, usp. this will yield a final concentration of 100 mcg/ml. withdraw an appropriate dose from the 100 mcg/ml solution prior to bolus intravenous administration. 2.3 preparing a solution for continuous intravenous infusion for continuous intravenous infusion, withdraw 10 mg (1 ml of 10 mg/ml concentration) of phenylephrine hydrochloride injection and add to 500 ml of 5% dextrose injection, usp or 0.9% sodium chloride injection, usp (providing a final concentration of 20 mcg/ml). 2.4 dosing for perioperative setting 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. 2.5 dosing for septic or other vasodilatory shock in adult patients with 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. 2.6 directions for dispensing from pharmacy bulk vial the pharmacy bulk vial is intended for dispensing of single doses to multiple patients in a pharmacy admixture program and is restricted to the preparation of admixtures for infusion. each closure shall be penetrated only one time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents. the pharmacy bulk vial is to be used only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). dispensing from a pharmacy bulk vial should be completed within 4 hours after the vial is penetrated.
2.6 directions for dispensing from pharmacy bulk vial the pharmacy bulk vial is intended for dispensing of single doses to multiple patients in a pharmacy admixture program and is restricted to the preparation of admixtures for infusion. each closure shall be penetrated only one time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents. the pharmacy bulk vial is to be used only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). dispensing from a pharmacy bulk vial should be completed within 4 hours after the vial is penetrated.
Dosage Forms and Strength:
3 dosage forms and strengths injection: 10 mg/ml phenylephrine hydrochloride is supplied in two vial sizes: 1 ml single dose vial (10 mg of phenylephrine hydrochloride per vial) 10 ml pharmacy bulk package vial (100 mg of phenylephrine hydrochloride per vial) that will provide ten 1 ml single doses injection: 10 mg/ml supplied as a: 1 ml single dose vial ( 3 , 1 1 , 16 ) 10 ml pharmacy bulk package vial ( 3 , 11 , 16 )
Contraindications:
4 contraindications the use of phenylephrine hydrochloride is contraindicated in patients with: hypersensitivity to it or any of its components hypersensitivity to it or any of its components ( 4 )
Adverse Reactions:
6 adverse reactions 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 most common adverse reactions: nausea and vomiting, headache, nervousness ( 6 ) to report
Read more... suspected adverse reactions, contact hikma pharmaceuticals usa inc. at 1-877-845-0689 or fda at 1-800-fda-1088 or www.fda.gov/medwatch .
Drug Interactions:
7 drug interactions agonistic effects with monoamine oxidase inhibitors (maoi), β-adrenergic blocking agents, α-2 adrenergic agonists, steroids, tricyclic antidepressants, norepinephrine transport inhibitors, ergot alkaloids, centrally-acting sympatholytic agents and atropine sulfate ( 7.1 ) antagonistic effects on and by α-adrenergic blocking agents ( 7.2 ) 7.1 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 7.2 antagonists α-adrenergic blocking agents, including phenothiazines (e.g., chlorpromazine) and amiodarone block phenylephrine and are in turn blocked by phenylephrine.
Read more... Use in Specific Population:
8 use in specific populations 8.1 pregnancy pregnancy category c animal reproduction studies have not been conducted with intravenous phenylephrine. it is also not known whether phenylephrine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. phenylephrine hydrochloride should be given to a pregnant woman only if clearly needed. 8.2 labor and delivery the most common maternal adverse reactions reported in studies of phenylephrine use during neuraxial anesthesia during cesarean delivery include nausea and vomiting, which are commonly associated with hypotension, bradycardia, reactive hypertension, and transient arrhythmias. phenylephrine does not appear to cause a decrease in placental perfusion sufficient to alter either the neonate apgar scores or blood-gas status. 8.3 nursing mothers it is not known whether this drug is excreted in human milk. 8.4 pediatric use safety and effectiveness in pediatric patients have not been established. 8.5 g
Read more...eriatric use clinical studies of phenylephrine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. 8.6 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. 8.7 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.
Use in Pregnancy:
8.1 pregnancy pregnancy category c animal reproduction studies have not been conducted with intravenous phenylephrine. it is also not known whether phenylephrine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. phenylephrine hydrochloride should be given to a pregnant woman only if clearly needed.
Pediatric Use:
8.3 nursing mothers it is not known whether this drug is excreted in human milk.
Geriatric Use:
8.4 pediatric use safety and effectiveness in pediatric patients have not been established.
Overdosage:
10 overdosage overdose of phenylephrine hydrochloride can cause a rapid rise in blood pressure. symptoms of overdose include headache, vomiting, hypertension, reflex bradycardia, and cardiac arrhythmias including ventricular extrasystoles and ventricular tachycardia, and may cause a sensation of fullness in the head and tingling of the extremities. consider using an α-adrenergic antagonist.
Description:
11 description 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: phenylephrine hydrochloride is very soluble in water, freely soluble in ethanol, and insoluble in chloroform and ethyl ether. phenylephrine hydrochloride is sensitive to light. phenylephrine hydrochloride injection, usp is a clear, colorless, aqueous solution that is essentially free of visible foreign matter. each ml contains: phenylephrine hydrochloride 10 mg; sodium chloride 3.5 mg; sodium citrate dihydrate 4 mg; citric acid monohydrate 1 mg; and sodium metabisulfite 2 mg in water for injection. the ph may be adjusted in the range of 3.0 to 6.5 with sodium hydroxide and/or hydrochloric acid, if necessary. structural formula
Clinical Pharmacology:
12 clinical pharmacology 12.1 mechanism of action phenylephrine hydrochloride is an α-1 adrenergic receptor agonist. 12.2 pharmacodynamics phenylephrine is the active moiety. metabolites are inactive at both the α-1and α-2 adrenergic receptors. following parenteral administration of phenylephrine hydrochloride, increases in systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, and total peripheral vascular resistance are observed. the onset of blood pressure increase following an intravenous bolus phenylephrine hydrochloride administration is rapid and the effect may persist for up to 20 minutes. as mean arterial pressure increases following parenteral doses, vagal activity also increases, resulting in reflex bradycardia. most vascular beds are constricted, including renal, splanchnic, and hepatic. 12.3 pharmacokinetics following an intravenous infusion of phenylephrine hydrochloride, the effective half-life was approximately 5 minutes. the steady-st
Read more...ate 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.
Mechanism of Action:
12.1 mechanism of action phenylephrine hydrochloride is an α-1 adrenergic receptor agonist.
Pharmacodynamics:
12.2 pharmacodynamics phenylephrine is the active moiety. metabolites are inactive at both the α-1and α-2 adrenergic receptors. following parenteral administration of phenylephrine hydrochloride, increases in systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, and total peripheral vascular resistance are observed. the onset of blood pressure increase following an intravenous bolus phenylephrine hydrochloride administration is rapid and the effect may persist for up to 20 minutes. as mean arterial pressure increases following parenteral doses, vagal activity also increases, resulting in reflex bradycardia. most vascular beds are constricted, including renal, splanchnic, and hepatic.
Pharmacokinetics:
12.3 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.
Clinical Studies:
14 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:
16 how supplied/storage and handling phenylephrine hydrochloride injection, usp, 10 mg/ml, is supplied as follows: ndc 72572-571-25: 1 ml single dose vials packaged in cartons containing 25 vials per carton ndc 72572-570-10: 10 ml pharmacy bulk package vials packed in cartons containing 10 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) [see usp controlled room temperature]. protect from light. keep covered in carton until time of use. the 1 ml vials are for single use only; the 10 ml vial is a pharmacy bulk package. the diluted solution should not be held for more than 4 hours at room temperature or for more than 24 hours under refrigerated conditions. discard any unused portion.
Information for Patients:
17 patient counseling information 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
Package Label Principal Display Panel:
Manufactured for: civica, inc., lehi, utah 84043 manufactured by: hikma pharmaceuticals usa inc. cherry hill, nj 08003 revised: july 2020 462-884-00
Principal display panel ndc 72572- 571 -01 phenylephrine hydrochloride inj., usp 10 mg/ml for intravenous use dilute before use protect from light 1 ml single dose vial ndc 72572-571-25 rx only phenylephrine hydrochloride inj. , usp 10 mg/ml for intravenous use dilute before use 25 x 1 ml single dose vials discard unused portion 1 ml thumb 1 ml x 25 thumb
Principal display panel ndc 72572- 570 -01 rx only phenylephrine hydrochloride inj., usp 100 mg/10 ml (10 mg/ml) pharmacy bulk package not for direct infusion for intravenous use must be diluted protect from light 10 ml vial ndc 72572- 570 -10 rx only phenylephrine hydrochloride inj., usp 100 mg/10 ml (10 mg/ml) pharmacy bulk package not for direct infusion for intravenous use must be diluted - protect from light store in carton until time of use 10 x 10 ml vials 10 ml thumb 10 ml x 10 thumb
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