Phenylephrine hydrochloride

Description

Phenylephrine Hydrochloride Injection contains phenylephrine as the active pharmaceutical ingredient in the form of its hydrochloride salt. Phenylephrine is a synthetic sympathomimetic agent provided in a sterile formulation for parenteral administration. The chemical structure of phenylephrine hydrochloride is represented as (-)-m-Hydroxy-α-(methylamino)methylbenzyl alcohol hydrochloride. This compound exhibits high solubility in water, is freely soluble in ethanol, and is insoluble in chloroform and ethyl ether. It is also sensitive to light.

The injection is presented as a clear, colorless, aqueous solution that is essentially free of visible foreign matter. Prior to administration, it must be diluted for either bolus intravenous infusion or continuous intravenous infusion. Each milliliter of the solution contains 10 mg of phenylephrine hydrochloride, 3.5 mg of sodium chloride, 4 mg of sodium citrate dihydrate, and 1 mg of citric acid, all in water for injection. The pH of the solution may be adjusted to a range of 3.5 to 5.5 using sodium hydroxide and/or hydrochloric acid, if necessary.

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

In cases of vasodilatory shock, the dosing regimen involves a continuous intravenous infusion starting at 0.5 mcg/kg/minute, which can be titrated up to a maximum of 6 mcg/kg/minute according to the clinical effect observed.

Healthcare professionals should monitor the patient's response closely and adjust the infusion rate as necessary 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.

Warnings and Precautions

Severe bradycardia and decreased cardiac output are significant risks associated with the use of this medication. Healthcare professionals should closely monitor patients for these cardiovascular effects, particularly in those with pre-existing heart conditions or those receiving concomitant medications that may exacerbate these issues.

Extravasation during intravenous administration poses a serious risk, as it may lead to necrosis or sloughing of tissue. It is imperative that healthcare providers ensure proper intravenous technique and monitor the infusion site closely to prevent this complication.

When this medication is used in conjunction with oxytocic drugs, there is a potentiation of the pressor effect of sympathomimetic pressor amines. Caution is advised when administering these agents together, and careful monitoring of blood pressure and heart rate is recommended to mitigate potential adverse effects.

No specific general precautions or laboratory tests have been identified for this medication; however, ongoing assessment of the patient's clinical status is essential to ensure safe and effective use.

Side Effects

Patients may experience a range of adverse reactions while using this medication. The most common adverse reactions reported include nausea and vomiting, headache, and nervousness.

Serious side effects have been identified, including severe bradycardia and decreased cardiac output. Extravasation during intravenous administration may lead to necrosis or sloughing of tissue. Additionally, caution is advised when using this medication concomitantly with oxytocic drugs, as the pressor effect of sympathomimetic pressor amines may be potentiated.

Allergic reactions, such as hypersensitivity to the product or any of its components, have also been observed.

In cases of overdosage, symptoms may include 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.

Long-term animal studies have shown no evidence of carcinogenicity in mice or rats, and phenylephrine hydrochloride has tested negative in various mutagenesis assays. Furthermore, no adverse effects on fertility or early embryonic development were noted in animal studies.

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 adverse effects.

Conversely, antagonistic interactions are noted with α-adrenergic blocking agents. The presence of these agents may diminish the intended effects of the drug, and dosage adjustments may be required based on clinical response. Monitoring for reduced efficacy is advised when these agents are used concurrently.

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, there was an increased incidence of agenesis of the intermediate lobe of the lung, a visceral variation, at doses as low as 0.08 times the HDD.

The estimated background risk of major birth defects and miscarriage in 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 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, with the highest dose being 0.3/0.2 times the HDD based on body surface area. However, maternal toxicity, including mortality, was observed 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, but no clear treatment-related malformations were identified. Maternal toxicity was evident, as indicated by decreased food consumption and body weight gain across all doses, along with an increased incidence of agenesis of the intermediate lobe of the lung 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 consider these findings when prescribing this medication to pregnant patients or women of childbearing potential, weighing the potential risks against the benefits.

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. There is currently no data available regarding the excretion of phenylephrine hydrochloride in human breast milk or its effects on breastfed infants. Therefore, healthcare professionals should weigh the potential benefits against any unknown risks when considering this medication for lactating mothers.

Renal Impairment

In patients with end stage renal disease (ESRD) undergoing hemodialysis, dose-response data indicates increased responsiveness to phenylephrine. Therefore, it is advisable to consider using lower doses of phenylephrine hydrochloride in this patient population to mitigate the risk of adverse effects associated with heightened sensitivity. Monitoring of these patients is essential to ensure appropriate dosing and to avoid potential complications related to reduced kidney function.

Hepatic Impairment

In patients with hepatic impairment, particularly those with liver cirrhosis classified under Child Pugh Class A, Class B, and Class C, there is evidence suggesting a decreased responsiveness to phenylephrine. Given this reduced responsiveness, it may be necessary to consider administering larger doses than typically recommended for these patients.

Monitoring of liver function is advised in patients with compromised hepatic function to ensure appropriate dosing and to assess the need for any adjustments. Careful evaluation of the patient's clinical status and response to treatment should guide any modifications in dosage.

Overdosage

In cases of overdose with phenylephrine hydrochloride injection (10 mg/mL), healthcare professionals should be aware that a rapid increase in blood pressure may occur. This hypertensive response can lead to a range of symptoms that require prompt attention.

Symptoms of Overdose Patients experiencing an overdose may present with a variety of symptoms, including headache, vomiting, and significant hypertension. Additionally, reflex bradycardia may be observed, along with 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.

Management of Overdose In the event of an overdose, it is advisable to consider the administration of an α-adrenergic antagonist to mitigate the effects of excessive phenylephrine. Continuous monitoring of the patient's cardiovascular status is essential, and supportive care should be provided as necessary. Immediate medical intervention may be required to address severe hypertension and associated complications.

Nonclinical Toxicology

Long-term animal studies conducted by the National Toxicology Program evaluated the carcinogenic potential of orally administered phenylephrine hydrochloride in F344/N rats and B6C3F1 mice. These studies utilized the dietary route of administration. The results indicated 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. Similarly, rats administered approximately 50 mg/kg/day, equivalent to 48 times the HDD based on body surface area comparisons, also showed no evidence of carcinogenicity.

In terms of mutagenesis, phenylephrine hydrochloride demonstrated a negative outcome 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 observed in one of two replicates of the in vitro mouse lymphoma assay.

Regarding impairment of fertility, no adverse effects were noted on fertility or early embryonic development when phenylephrine hydrochloride was administered at doses of 50 mcg, 100 mcg, or 200 mcg/kg/day. These doses, which were administered 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, corresponded to up to 0.2 times the HDD of 10 mg/60 kg/day based on body surface area.

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 complications such as heart block, other cardiac arrhythmias, 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 (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 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 tissue. Other symptoms to discuss 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 essential for healthcare providers to ensure that patients understand these potential side effects and to encourage them to report any concerning symptoms promptly.

Storage and Handling

The product is supplied in a configuration that allows for single use only. It is essential to store the product at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) as defined by 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. Any unused portion should be discarded after use to maintain safety and efficacy.

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 Fresenius Kabi USA, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)