Phenylephrine hydrochloride

Description

Phenylephrine Hydrochloride Injection contains phenylephrine as the active pharmaceutical ingredient in the form of hydrochloride salt. It 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 is freely soluble in water and ethanol, but it is sensitive to light.

The formulation of Phenylephrine Hydrochloride Injection, USP, is a clear, colorless solution that is essentially free of visible foreign matter, with a concentration of 10 mg/mL. Each milliliter contains 10 mg of Phenylephrine Hydrochloride USP, which is equivalent to 8.2 mg of phenylephrine base. Additionally, the injection includes 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 used as pH adjusters in Water for Injection. The pH range of Phenylephrine Hydrochloride Injection is between 3.0 and 6.5.

Uses and Indications

Phenylephrine Hydrochloride Injection 10 mg/mL is indicated for increasing blood pressure in adults experiencing clinically important hypotension primarily due to vasodilation in the contexts of anesthesia and septic shock.

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

Dosage and Administration

Prior to administration, the solution must be diluted.

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 to 1.4 mcg/kg/minute, with titration based on the patient's response.

In patients experiencing vasodilatory shock, the dosing regimen involves a continuous intravenous infusion starting at 0.5 mcg/kg/minute, which may be increased up to 6 mcg/kg/minute, also titrated to achieve the desired clinical effect.

Contraindications

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

Warnings and Precautions

Severe bradycardia and decreased cardiac output may occur 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 can lead to serious complications, including necrosis or sloughing of tissue. It is imperative to ensure proper intravenous technique and to monitor the injection site for any signs of extravasation.

Caution is advised when administering this medication concomitantly with oxytocic drugs, as the pressor effect of sympathomimetic pressor amines may be potentiated. Healthcare providers should evaluate the potential risks and benefits of such combinations and monitor patients accordingly.

Allergic-type reactions may occur with Phenylephrine Hydrochloride Injection 10 mg/mL, particularly in individuals sensitive to sulfites. It is essential to assess patients for any history of sulfite allergies prior to administration and to be prepared to manage any allergic reactions that may arise.

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, with nervousness occurring in approximately 6% of participants.

Serious adverse reactions can include severe bradycardia and decreased cardiac output, which are critical considerations during treatment. Additionally, extravasation during intravenous administration may lead to necrosis or sloughing of tissue, necessitating careful monitoring of the administration site.

The concomitant use of this medication with oxytocic drugs has been noted to potentiate the pressor effect of sympathomimetic pressor amines, which may require dose adjustments or careful patient management.

Allergic-type reactions have been observed with Phenylephrine Hydrochloride Injection 10 mg/mL, particularly in patients with hypersensitivity to the products or any of their components, including sulfite.

In cases of overdose, symptoms may include headache, vomiting, hypertension, reflex bradycardia, cardiac arrhythmias such as ventricular extrasystoles and ventricular tachycardia, as well as sensations of fullness in the head and tingling of the extremities. These symptoms highlight the importance of adhering to recommended dosing guidelines to minimize the risk of adverse effects.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there are no known interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are necessary 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 patients. However, other reported clinical experience has not identified significant differences in responses between elderly patients and their younger counterparts.

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, there was an increased incidence of agenesis of the intermediate lobe of the lung, a visceral variation, at levels as low as 0.08 times the HDD. The estimated background risk of major birth defects and miscarriage for the indicated population remains unknown; however, it is acknowledged 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 noted 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. However, evidence of maternal toxicity, including mortality, was observed at the highest tested dose of 300/200 mcg/kg. Similarly, in normotensive pregnant rabbits treated with a single daily intravenous bolus dose of 40 mcg, 100 mcg, and 200 mcg/kg from Gestation Day 7 to 19, decreased fetal body weights were reported, along with maternal toxicity characterized by decreased food consumption and body weight gain at all doses. An increased incidence of agenesis of the intermediate lobe of the lung was noted in all treatment groups compared to controls.

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 from Gestation Day 6 to Lactation Day 20. Given these findings, healthcare professionals should consider the potential risks and benefits when prescribing this medication to pregnant patients.

Lactation

There are no specific statements regarding nursing mothers or lactation in the provided text. Therefore, the effects of this medication on lactating mothers and breastfed infants are not established. Healthcare professionals should consider the lack of data when advising lactating mothers on the use of this medication.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring of these patients.

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 outlined 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 is a significant concern. Healthcare professionals should be vigilant for symptoms that may arise, which include headache, vomiting, and hypertension.

Additionally, reflex bradycardia may occur, along with potential cardiac arrhythmias such as ventricular extrasystoles and ventricular tachycardia.

Management of phenylephrine overdose should focus on monitoring the patient's vital signs closely and providing supportive care. It is essential to implement appropriate interventions to stabilize blood pressure and address any arrhythmias that may develop. Continuous cardiac monitoring is recommended to detect and manage any serious cardiac complications promptly.

Nonclinical Toxicology

No adverse effects on fertility or early embryonic development were observed in studies where phenylephrine hydrochloride was administered at doses of 50 mcg, 100 mcg, or 200 mcg/kg/day. This administration occurred via single daily bolus injection for 28 days prior to mating in male rats and for 14 days prior to mating through Gestation Day 7 in female rats, corresponding to up to 0.2 times the human daily dose (HDD) of 10 mg/60 kg/day based on body surface area.

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 based on body surface area, or in rats receiving approximately 50 mg/kg/day, equivalent to 48 times the human daily dose.

In terms of mutagenesis, phenylephrine hydrochloride tested negative in several assays, including the in vitro bacterial reverse mutation assay using S. typhimurium strains TA98, TA100, TA1535, and TA1537, the in vitro chromosomal aberrations assay, the in vitro sister chromatid exchange assay, and the in vivo rat micronucleus assay. However, positive results were noted in one of two replicates of the in vitro mouse lymphoma assay.

Postmarketing Experience

Postmarketing experience has identified hypertension as the primary side effect associated with phenylephrine, with rare occurrences of hypertensive crisis. Additionally, bradycardia has been reported, which may lead to 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.

Common, less serious adverse events include chest pain, skin or tissue damage resulting from extravasation of the drug from the venous catheter, headache, nervousness, tremor, and paresthesias in the hands or feet. Other reported symptoms encompass nausea, vomiting, excitability, dizziness, sweating, and flushing.

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 essential 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.

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

It is crucial for healthcare providers to encourage patients to report any concerning symptoms promptly and to ensure they understand the importance of monitoring their condition while receiving treatment with phenylephrine.

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°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F) in accordance with USP Controlled Room Temperature guidelines.

To ensure product integrity, the vials should be protected from light and kept covered in their original 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 2°C to 8°C. Any unused diluted solution must also be discarded.

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 Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)