Phenylephrine hydrochloride

Description

Phenylephrine Hydrochloride Injection contains phenylephrine as the active pharmaceutical ingredient in the form of its hydrochloride salt. It is a synthetic sympathomimetic agent provided in a sterile formulation for parenteral administration. The chemical name of phenylephrine hydrochloride is (-)-m-Hydroxy-α-(methylamino)methylbenzyl alcohol hydrochloride, and its structural formula is represented accordingly.

This injection is characterized as a clear, colorless, aqueous solution that is essentially free of visible foreign matter, with a concentration of 10 mg/mL of phenylephrine hydrochloride, which is equivalent to 8.2 mg of phenylephrine base. Each milliliter also contains 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 USP as an antioxidant. Sodium Hydroxide NF and Hydrochloric Acid NF are included as pH adjusters in Water for Injection, resulting in a pH range of 3.0 to 6.5.

Phenylephrine hydrochloride is freely soluble in water and alcohol but is sensitive to light. It is essential to dilute the solution prior to administration, whether as a bolus intravenous infusion or a continuous intravenous infusion.

Uses and Indications

Phenylephrine Hydrochloride Injection 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

The product must be diluted prior to administration to ensure safe and effective delivery.

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 1.4 mcg/kg/minute 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, with the possibility of titration up to 6 mcg/kg/minute, again guided by the clinical effect observed in the patient.

Healthcare professionals should closely monitor the patient's response and adjust the infusion rate accordingly to achieve the desired therapeutic effect.

Contraindications

Use of this product is contraindicated in individuals with hypersensitivity to the product or any of its components. Due to the potential for severe allergic reactions, patients with a known history of such hypersensitivity should not use this product.

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 signs of bradycardia and assess cardiac output, particularly in those with pre-existing cardiovascular conditions.

Extravasation during intravenous administration of this medication may lead to serious complications, including necrosis or sloughing of tissue. It is imperative to ensure proper intravenous placement and to monitor the infusion site regularly to prevent 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 for enhanced hypertensive responses.

Patients may experience allergic-type reactions due to the presence of sulfite in Phenylephrine Hydrochloride Injection 10 mg/mL. It is essential to inquire about any known sulfite allergies prior to administration and to observe patients for signs of an allergic reaction during and after the infusion.

Side Effects

Patients may experience a range of adverse reactions associated with the use of this medication. The most common adverse reactions reported include nausea and vomiting, headache, and nervousness.

Severe adverse reactions have also been observed. These include severe bradycardia and decreased cardiac output, which may pose significant risks to patients. Extravasation during intravenous administration can lead to necrosis or sloughing of tissue, necessitating careful monitoring during administration. Additionally, the concomitant use of this medication with oxytocic drugs may potentiate the pressor effect of sympathomimetic pressor amines, which requires caution. Allergic-type reactions have been noted with Phenylephrine Hydrochloride Injection 10 mg/mL, particularly in patients with sulfite sensitivity.

Other important considerations include hypersensitivity reactions to the products or any of their components. In cases of overdose, symptoms may manifest as headache, vomiting, hypertension, reflex bradycardia, cardiac arrhythmias (including ventricular extrasystoles and ventricular tachycardia), a sensation of fullness in the head, and tingling of the extremities. Monitoring for these adverse reactions is essential to ensure patient safety.

Drug Interactions

The use of this medication may result in significant drug interactions, categorized primarily into agonistic and antagonistic effects.

Agonistic interactions are observed with the following drug classes: monoamine oxidase inhibitors (MAOIs), β-adrenergic blocking agents, α-2 adrenergic agonists, steroids, tricyclic antidepressants, norepinephrine transport inhibitors, ergot alkaloids, centrally-acting sympatholytic agents, and atropine sulfate. Co-administration with these agents may enhance the pharmacological effects, necessitating careful monitoring of the patient's response and potential dose adjustments.

Conversely, antagonistic interactions may occur with α-adrenergic blocking agents. The presence of these agents may diminish the therapeutic effects of the medication, warranting consideration of alternative therapies or dosage modifications based on clinical response.

Healthcare professionals are advised to monitor patients closely for any signs of altered efficacy or adverse effects when these interactions are anticipated.

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, 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 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.

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. Given these findings, healthcare professionals should weigh the potential risks and benefits when considering the use of this medication in pregnant patients.

Lactation

There are no reported adverse effects on breastfed infants when lactating mothers are treated with phenylephrine hydrochloride. In studies involving pregnant rats, administration of a single daily intravenous bolus dose of up to 200 mcg/day (0.2 times the human equivalent dose based on body surface area) from Gestation Day 6 to Lactation Day 20 did not result in negative outcomes for the offspring. Therefore, the use of phenylephrine hydrochloride in lactating mothers may be considered safe based on available animal data.

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.

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 is a significant concern. Healthcare professionals should be vigilant for symptoms that may arise, which include headache, vomiting, hypertension, reflex bradycardia, and various cardiac arrhythmias such as ventricular extrasystoles and ventricular tachycardia.

Patients may also report a sensation of fullness in the head and tingling in the extremities, which can further indicate the severity of the overdose.

Management of phenylephrine overdose may involve the administration of an α-adrenergic antagonist to counteract the effects of the overdose. It is essential for healthcare providers to monitor the patient closely and provide supportive care as needed.

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 (up to 0.2 times the human daily dose of 10 mg/60 kg/day based on body surface area) 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 (131 times the human daily dose based on body surface area) or in rats receiving approximately 50 mg/kg/day (48 times the human daily dose 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. Positive results were noted in only one of two replicates of the in vitro mouse lymphoma assay.

No specific details regarding animal pharmacology were provided in the available data.

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 and myocardial ischemia in patients with pre-existing cardiac conditions. Cases of pulmonary edema and rales have also been noted.

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 (numbness or tingling) in the extremities. 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 important to discuss the potential for bradycardia, which can result in heart block or other cardiac arrhythmias, particularly in patients with pre-existing cardiac conditions. Additionally, patients should be made aware of the risk of myocardial ischemia and pulmonary edema, which may manifest as fluid in the lungs or rales.

Providers should also communicate that while some side effects are less serious, they can still impact the patient's well-being. These may include chest pain, skin or tissue damage if the drug leaks from the venous catheter into surrounding tissue, and neurological symptoms such as headache, nervousness, tremor, and numbness or tingling (paresthesias) in the hands or feet. Patients may also experience gastrointestinal symptoms like nausea and vomiting, as well as general symptoms including excitability, dizziness, sweating, and flushing.

It is essential for healthcare providers to ensure that patients understand these potential side effects and encourage them to report any concerning symptoms 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 should be stored 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, it must be protected from light and kept covered in its carton until the time of use. Once diluted, the solution 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 should 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 Novadoz Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)