Dilution Neosynephrine ® - Phenylephrine

Phenylephrine (Neosynephrine ®)

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Usual Diluents

NS (preferred) , D5W (less support)

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

Standard Dilutions:
[Concentration: 0.1 mg/ml - 0.9NS. Stability 14 days at room temperature ] ¹:
[25 mg] [250 ml] [Titrate] or [50 mg] [500 ml] [Titrate]OR[Concentration: 0.2 mg/ml -0.9NS. Stability 14 days RT-possibly up to 60 days RT]^1,2:
[50 mg] [250 ml] [Titrate] or [100 mg] [500 ml] [Titrate]
---------------------Other:
Minimum dilution:
[Concentration: 0.4 mg/ml -0.9NS. Stability 60 days RT]²:
[40 mg] [100 ml] [Titrate]

Package insert:
D5W or 0.9NS - stability unknown³.
[10 mg] [500 ml] [Titrate]

Reference data for updated dilution standards:
1] Gupta VD. Chemical Stability of Phenylephrine Hydrochloride After Reconstitution in 0.9% Sodium Chloride Injection for Infusion. Int J Pharm Compd. 2004 March-April;8(2):153-155.

Abstract
"The chemical stability of phenylephrine hydrochloride (0.2 and 0.1 mg/mL) in 0.9% sodium chloride injection stored in polyvinyl chloride bags was studied at 25 deg C by means of a stability-indicating high-performance liquid chromatographic assay method. The concentrations of the drug were directly related to peak heights, and the percent relative standard deviation based on five injections was 1.0. The excipients present in the injection did not interfere with the assay procedure. The products of decomposition separated from the intact drug. At both concentrations (0.2 and 0.1 mg/mL), the loss in potency was less than 1.0% after 14 days of storage at room temperature. The pH value of the 0.2-mg/mL injection decreased from 4.3 to 4.0 after 14 days of storage, and the pH value of the 0.1-mg/mL injection decreased from 4.4 to 4.2.The physical appearance of the injection did not change."

2] Jansen JJ, Oldland AR, Kiser TH. Evaluation of phenylephrine stability in polyvinyl chloride bags. Hosp Pharm. 2014 May;49(5):455-7. doi: 10.1310/hpj4905-455.

Abstract
"PURPOSE:
Phenylephrine hydrochloride (HCl) is commonly used to maintain adequate blood pressure during shock and shocklike states. Phenylephrine is prepared in concentrated stock vials that require further dilution prior to administration. This study evaluated the physical and chemical stability of phenylephrine in extemporaneously prepared polyvinyl chloride (PVC) bags.
METHODS:
Phenylephrine HCl 10 mg/mL solution was diluted with 0.9% sodium chloride for injection to final concentrations of 200 mcg/mL and 400 mcg/mL and stored at room temperature (23°C-25°C) exposed to fluorescent light. Stability of phenylephrine HCl was evaluated by high-performance liquid chromatography on days 0, 7, 14, 21, 30, 45, and 60.
RESULTS:
Phenylephrine HCl 200 and 400 mcg/mL solutions in PVC bags were physically stable during the entire 60-day study period. Phenylephrine HCl retained > 95% of the original concentration.
CONCLUSION:
Phenylephrine HCl diluted to 200 or 400 mcg/mL with 0.9% sodium chloride for injection is both physically and chemically stable for a period of 60 days with ≤5% degradation when stored at room temperature and exposed to fluorescent lighting."

3] Product Information (current packaging): PHENYLEPHRINE HYDROCHLORIDE- phenylephrine hydrochloride injection. Baxter Healthcare Corporation, Deerfield, IL 60015; 2014.

Add 10 mg of the drug (1 mL of 1 percent solution) to 500 mL of Dextrose Injection, USP or Sodium Chloride Injection.

Central line required. Peripheral line may be used for short periods (Max concentration: 10mg/250 ml) while preparation for central line is underway.

Stability / Miscellaneous

Label: Do not Refrigerate.

(Alpha agonist). May be given IM,SC, IV push, or by continuous infusion. Treat mild/moderate hypotension, also PSVT.

IV infusion: usual initial rate: 0.1 to 0.18 mg/min (100 to 180mcg/min) (titrate). Usual maintenance rate: 40-60 mcg/min.

-[Lexi-Comp, Inc. (Lexi-Drugs); October 2014]:
Usual maximum dosing range reported: 0.4 to 9.1 mcg/kg/minute-[Micromedex (DRUGDEX® System) - accessed (12/2014)]:
Usual range: 0.5 to 6 mcg/kg/min IV continuous infusion, titrate to blood pressure goal; no increase in efficacy above 6 mcg/kg/min.

IV bolus therapy: usual dose: 0.5 mg [range: 0.1 to 1 mg (max)] repeat q10-15 min as needed.

PSVT: 0.5 mg rapid IV push, subsequent doses may be increased in increments of 0.1 to 0.2mg.
------
DESCRIPTION
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.

CLINICAL PHARMACOLOGY
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.

ADVERSE REACTIONS
Headache, reflex bradycardia, excitability, restlessness and rarely arrhythmias.

DOSAGE AND ADMINISTRATION
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.

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 phenothiazines 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.

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.

Prolongation of Spinal Anesthesia
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.

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.

Source:
Product Information (current packaging): PHENYLEPHRINE HYDROCHLORIDE- phenylephrine hydrochloride injection. Baxter Healthcare Corporation, Deerfield, IL 60015; 2014.