Phenylephrine hydrochloride

Description

Phenylephrine hydrochloride injection contains the active pharmaceutical ingredient phenylephrine in the form of its hydrochloride salt. Phenylephrine is a synthetic sympathomimetic agent provided in sterile form for parenteral injection. The chemical name of phenylephrine hydrochloride is (-)-m-Hydroxy-α-(methylamino)methylbenzyl alcohol hydrochloride. This compound appears as a white or practically white powder and is very soluble in water, freely soluble in ethanol, and insoluble in chloroform and ethyl ether. It is sensitive to light.

Phenylephrine Hydrochloride Injection, USP, is formulated as a clear, colorless, aqueous solution at a concentration of 10 mg/mL, which is essentially free of visible foreign matter. Each mL of the injection contains 10 mg of phenylephrine hydrochloride USP (equivalent to 8.2 mg of phenylephrine base), along with 3.5 mg of Sodium Chloride USP as a tonicity agent, 1 mg of Citric Acid Monohydrate USP and 4 mg of Sodium Citrate Dihydrate USP as buffering agents, and 2 mg of Sodium Metabisulfite NF as an antioxidant. Sodium Hydroxide NF and Hydrochloric Acid NF are included as pH adjusters in Water for Injection. The pH range of phenylephrine hydrochloride injection is 3.5 to 5.5.

Uses and Indications

Phenylephrine hydrochloride injection is indicated for increasing blood pressure in adults with clinically important hypotension resulting primarily from vasodilation in the settings of anesthesia and septic shock.

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

Prior to administration, the medication must be diluted appropriately.

For the management of perioperative hypotension, the recommended dosing is as follows: an intravenous bolus of 50 mcg to 250 mcg may be administered. Alternatively, a continuous intravenous infusion can be initiated at a rate of 0.5 mcg/kg/minute, with titration up to a maximum of 1.4 mcg/kg/minute based on the patient's response.

In patients experiencing vasodilatory shock, the continuous intravenous infusion should be started at a rate of 0.5 mcg/kg/minute, with the possibility of titration up to 6 mcg/kg/minute, again guided by the clinical effect observed.

Contraindications

Use of this product is contraindicated in individuals with a known hypersensitivity to the product or any of its components.

Warnings and Precautions

Severe bradycardia and decreased cardiac output have been observed with the use of this medication. Healthcare professionals should monitor patients closely for these cardiovascular effects, particularly in those with pre-existing heart conditions.

Extravasation during intravenous administration of the medication may lead to necrosis or sloughing of tissue. It is imperative to ensure proper intravenous technique and to monitor the infusion site for any signs of extravasation.

Concomitant use with oxytocic drugs may potentiate the pressor effect of sympathomimetic pressor amines. Caution is advised when administering this medication alongside oxytocic agents, and appropriate monitoring of blood pressure and heart rate is recommended.

Allergic-type reactions may occur with Phenylephrine Hydrochloride Injection 10 mg/mL, particularly in individuals sensitive to sulfites. Healthcare providers should be vigilant for signs of an allergic reaction and be prepared to manage such events promptly.

Side Effects

Patients receiving treatment may experience a range of adverse reactions. The most common adverse reactions reported include nausea and vomiting, headache, and nervousness.

Serious side effects have also been observed. These include severe bradycardia and decreased cardiac output, which may require immediate medical attention. Extravasation during intravenous administration can lead to necrosis or sloughing of tissue. Additionally, the concomitant use of this medication with oxytocic drugs may potentiate the pressor effect of sympathomimetic pressor amines. Allergic-type reactions have been noted, particularly with Phenylephrine Hydrochloride Injection 10 mg/mL, which may be associated with sulfite sensitivity. Hypersensitivity to the products or any of their components has also been reported.

In cases of overdose, patients may exhibit symptoms such as headache, vomiting, hypertension, reflex bradycardia, and cardiac arrhythmias, including ventricular extrasystoles and ventricular tachycardia. Other symptoms may include a sensation of fullness in the head and tingling of the extremities. It is important for healthcare providers to monitor for these adverse reactions and manage them appropriately.

Drug Interactions

There are currently no documented drug interactions associated with the use of this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

Packaging & NDC

The table below lists all NDC Code configurations of Phenylephrine Hydrochloride, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Therefore, the use of this medication in children, infants, and adolescents should be approached with caution until further data is available.

Geriatric Use

Clinical studies of phenylephrine did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience has not identified significant differences in responses between elderly patients and younger patients.

In general, dose selection for geriatric patients should be approached with caution. It is advisable to start at the low end of the dosing range, taking into account the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies. Careful monitoring of these patients is recommended to ensure safety and efficacy.

Pregnancy

In animal reproductive and developmental studies, decreased fetal body weights were observed at doses equivalent to 0.4 times the human daily dose (HDD) of 10 mg. While no malformations were reported, an increased incidence of agenesis of the intermediate lobe of the lung, a visceral variation, was noted at levels as low as 0.08 times the HDD.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. It is important to note that all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2 to 4% and 15 to 20%, respectively.

In studies involving normotensive pregnant rats, no malformations were observed when treated with a single daily intravenous bolus dose of phenylephrine hydrochloride at doses of 50 mcg, 150 mcg, or 300/200 mcg/kg from Gestation Day 6 to 17, with the highest dose being 0.3/0.2 times the HDD based on body surface area. However, maternal toxicity, including mortality, was noted at the highest tested dose.

Similarly, in normotensive pregnant rabbits treated with phenylephrine hydrochloride at doses of 40 mcg, 100 mcg, and 200 mcg/kg (0.08, 0.2, and 0.4 times the HDD) from Gestation Day 7 to 19, decreased fetal body weights were reported without clear treatment-related malformations. Maternal toxicity was evident, as indicated by decreased food consumption and body weight gain across all doses, and an increased incidence of agenesis of the intermediate lobe of the lung was observed in all treatment groups compared to controls.

Conversely, no adverse effects on the offspring were reported when pregnant rats were treated with a single daily intravenous bolus dose of up to 200 mcg/day phenylephrine hydrochloride (0.2 times the HDD) from Gestation Day 6 to Lactation Day 20.

Healthcare professionals should weigh the potential risks and benefits when considering the use of this medication in pregnant patients.

Lactation

Lactating mothers may use phenylephrine hydrochloride, as no adverse effects on the offspring were reported in studies involving pregnant rats treated with a single daily intravenous bolus dose of up to 200 mcg/day. This dosage corresponds to 0.2 times the human equivalent dose based on body surface area and was administered from Gestation Day 6 to Lactation Day 20.

While specific data on excretion in human breast milk and effects on breastfed infants are not provided, the absence of reported adverse effects in animal studies may suggest a favorable safety profile. Healthcare professionals should consider the potential benefits and risks when advising lactating mothers on the use of this medication.

Renal Impairment

There is no specific information regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In cases of overdose with phenylephrine hydrochloride injection at a concentration of 10 mg/mL, a rapid increase in blood pressure may occur. Healthcare professionals should be vigilant for the following symptoms associated with overdose: headache, vomiting, hypertension, reflex bradycardia, and various cardiac arrhythmias, which may include ventricular extrasystoles and ventricular tachycardia.

Management of phenylephrine overdose should focus on the immediate stabilization of the patient. Continuous monitoring of vital signs is essential, particularly blood pressure and heart rate. If hypertension is present, appropriate antihypertensive measures should be initiated. In cases of significant cardiac arrhythmias, advanced cardiac life support (ACLS) protocols may be necessary, including the use of antiarrhythmic medications as indicated.

It is crucial for healthcare providers to assess the severity of the overdose and to implement supportive care as needed. Prompt recognition and intervention can mitigate the potential complications associated with phenylephrine overdose.

Nonclinical Toxicology

No teratogenic effects were observed in studies involving phenylephrine hydrochloride. Additionally, no adverse effects on fertility or early embryonic development were noted when phenylephrine hydrochloride was administered at doses of 50 mcg, 100 mcg, or 200 mcg/kg/day via single daily bolus injection for 28 days prior to mating in male rats or for 14 days prior to mating through Gestation Day 7 in female rats.

Long-term animal studies conducted by the National Toxicology Program assessed the carcinogenic potential of orally administered phenylephrine hydrochloride in F344/N rats and B6C3F1 mice. These studies revealed no evidence of carcinogenicity in mice receiving approximately 270 mg/kg/day, which is 131 times the human daily dose (HDD) of 10 mg/day based on body surface area, or in rats receiving approximately 50 mg/kg/day, equivalent to 48 times the HDD based on body surface area comparisons.

Phenylephrine hydrochloride demonstrated a negative outcome in the in vitro bacterial reverse mutation assay using S. typhimurium strains TA98, TA100, TA1535, and TA1537, as well as in the in vitro chromosomal aberrations assay, the in vitro sister chromatid exchange assay, and the in vivo rat micronucleus assay. However, positive results were reported in one of two replicates of the in vitro mouse lymphoma assay.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of phenylephrine, reported voluntarily or through surveillance programs. The primary side effect noted is hypertension, which may, in rare instances, escalate to a hypertensive crisis. Additionally, patients have reported experiencing bradycardia, which can lead to heart block or other cardiac arrhythmias.

Other cardiovascular events include extra ventricular beats and myocardial ischemia, particularly in individuals with pre-existing cardiac conditions. Respiratory complications such as pulmonary edema and rales have also been documented.

Common, less serious symptoms reported include chest pain, skin or tissue damage resulting from extravasation of the drug from the venous catheter, headache, nervousness, tremor, and paresthesias (numbness or tingling) in the extremities. Gastrointestinal symptoms such as nausea and vomiting, along with neuropsychiatric effects including excitability, dizziness, sweating, and flushing, have also been observed.

Patient Counseling

Healthcare providers should inform patients, families, or caregivers that the primary side effect of phenylephrine is hypertension, which may, in rare cases, lead to a hypertensive crisis. It is important to discuss the potential for bradycardia, which can result in heart block or other cardiac arrhythmias, as well as extra ventricular beats, myocardial ischemia in patients with pre-existing cardiac conditions, and pulmonary edema or rales.

Patients should be made aware of common, less serious symptoms that may occur, including chest pain, which could indicate complications. Providers should also explain the risk of skin or tissue damage if the medication leaks from the venous catheter into surrounding tissues. Other symptoms to discuss include headache, nervousness, tremor, and numbness or tingling (paresthesias) in the hands or feet, as well as gastrointestinal symptoms such as nausea and vomiting. Additionally, patients may experience excitability, dizziness, sweating, and flushing.

It is essential for healthcare providers to ensure that patients understand these potential side effects and symptoms, enabling them to recognize and report any adverse reactions promptly.

Storage and Handling

The product is supplied in 1 mL vials, which are intended for single-dose use only. Any unused portion must be discarded. It is essential to store the vials at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. The vials should be protected from light and kept covered in their carton until the time of use.

Once the solution has been diluted, it should not be held for more than 4 hours at room temperature or for more than 24 hours when refrigerated at temperatures between 2°C and 8°C. Proper adherence to these storage and handling instructions is crucial to ensure the integrity and efficacy of the product.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Phenylephrine Hydrochloride as submitted by Eugia US LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)