Phenylephrine hydrochloride

Description

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

This injection is characterized by its very high solubility in water, free solubility in ethanol, and insolubility in chloroform and ethyl ether. It is sensitive to light. Phenylephrine Hydrochloride Injection, USP is formulated at a concentration of 10 mg per mL and appears as a clear, colorless aqueous solution that is essentially free of visible foreign matter.

Prior to administration, the solution must be diluted for either bolus intravenous infusion or continuous intravenous infusion. Each mL of the injection contains 10 mg of phenylephrine hydrochloride (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, resulting in a pH range of 3.0 to 6.5.

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

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, with titration to effect up to a maximum of 1.4 mcg/kg/minute.

In patients experiencing vasodilatory shock, the dosing regimen involves a continuous intravenous infusion starting at 0.5 mcg/kg/minute, with titration to effect permissible up to 6 mcg/kg/minute.

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

Contraindications

Use of this product is contraindicated in individuals with a known hypersensitivity to the product or any of its components. This contraindication is based on the potential for severe allergic reactions, which may pose significant health risks.

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 poses a significant risk, as it 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.

Caution is advised when administering this medication concomitantly with oxytocic drugs, as the pressor effect of sympathomimetic pressor amines may be potentiated. This interaction necessitates careful monitoring of blood pressure and heart rate in patients receiving both therapies.

Allergic-type reactions may occur with phenylephrine hydrochloride injection (10 mg per 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 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 require immediate medical attention. 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 could pose significant risks. Allergic-type reactions have been noted with the use of phenylephrine hydrochloride injection (10 mg per 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 a rapid rise in blood pressure, headache, vomiting, hypertension, reflex bradycardia, cardiac arrhythmias (including ventricular extrasystoles and ventricular tachycardia), as well as sensations of fullness in the head and tingling of the extremities. Monitoring for these adverse reactions is essential to ensure patient safety and effective management.

Drug Interactions

The interaction profile includes both agonistic and antagonistic effects with various drug classes.

Agonistic interactions are observed with the following agents: 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. Clinicians should be aware of the potential for enhanced pharmacological effects when these agents are co-administered, which may necessitate careful monitoring of therapeutic outcomes and side effects.

Conversely, antagonistic interactions are noted with α-adrenergic blocking agents. The presence of these agents may diminish the therapeutic efficacy of the drug, and clinicians should consider dosage adjustments or alternative therapies based on the clinical context and patient response. Regular monitoring of the patient's condition is advised to ensure optimal therapeutic management.

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 remains unknown. It is important to recognize 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

There are no reported adverse effects on breastfed infants when lactating mothers are treated with phenylephrine hydrochloride. In animal studies, pregnant rats administered 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 show any negative outcomes in their offspring.

Healthcare professionals should consider this information when evaluating the use of phenylephrine hydrochloride in lactating mothers.

Renal Impairment

Patients with renal impairment may not have specific information regarding dosage adjustments, special monitoring, or safety considerations outlined in the prescribing information. Therefore, healthcare professionals should exercise caution when prescribing this medication to individuals with reduced kidney function, as the absence of detailed guidance 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 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 (10 mg per 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. Notably, patients may experience ventricular extrasystoles and ventricular tachycardia, along with sensations of fullness in the head and tingling in the extremities.

Management of phenylephrine overdose should include the consideration of an α-adrenergic antagonist to mitigate the effects of excessive adrenergic stimulation. Continuous monitoring of cardiovascular status is essential, and appropriate supportive measures should be implemented based on the severity of symptoms presented.

Nonclinical Toxicology

No information is available regarding teratogenic effects associated with phenylephrine hydrochloride.

Non-teratogenic effects were observed in studies where 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 and for 14 days prior to mating through Gestation Day 7 in female rats. No adverse effects on fertility or early embryonic development were noted at these doses, which correspond to up to 0.2 times the human daily dose 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. The 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 based on body surface area comparisons.

Phenylephrine hydrochloride was tested in various genotoxicity assays. It tested negative 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 and the in vitro sister chromatid exchange assay. Additionally, the in vivo rat micronucleus assay yielded negative results. However, positive results were observed 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 hydrochloride injection, 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 or 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/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 associated with phenylephrine hydrochloride injection is hypertension, which may, in rare cases, lead to a hypertensive crisis. It is important to discuss the potential for bradycardia, which is characterized by a slow heart rate and may result in heart block or other cardiac arrhythmias. Patients with underlying cardiac disease should be made aware of the risk of myocardial ischemia and pulmonary edema, which may present as fluid in the lungs or rales.

Providers should also communicate that while some symptoms may be less serious, they can still be concerning. Patients should be advised to report any occurrence of chest pain, as well as any signs of skin or tissue damage that may arise if the medication leaks from the venous catheter into surrounding tissue. Other common symptoms that may occur include headache, nervousness, tremor, and numbness or tingling (paresthesias) in the hands or feet. Additionally, patients should be made aware of the possibility of experiencing nausea, vomiting, excitability, dizziness, sweating, and flushing.

It is essential for healthcare providers to ensure that patients understand these potential side effects and encourage them to seek medical attention if they experience any severe or concerning symptoms.

Storage and Handling

The product is supplied in packaging that adheres to the National Drug Code (NDC) specifications. 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 it is ready for 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 portion of the diluted solution should 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 Meitheal Pharmaceuticals Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)