Phenylephrine hydrochloride

Description

Phenylephrine hydrochloride is a synthetic sympathomimetic agent formulated for parenteral injection. Its chemical structure is defined as (-)-m-Hydroxy-α-(methylamino)methylbenzyl alcohol hydrochloride. The compound has a high solubility profile, being very soluble in water, freely soluble in ethanol, and insoluble in chloroform and ethyl ether. It is also sensitive to light.

Phenylephrine Hydrochloride Injection, USP is presented as a clear, colorless, aqueous solution that is essentially free of visible foreign matter. Each milliliter of the solution contains 10 mg of phenylephrine hydrochloride, along with 3.5 mg of sodium chloride, 4 mg of sodium citrate dihydrate, 1 mg of citric acid monohydrate, and 2 mg of sodium metabisulfite, all in water for injection. The pH of the solution may be adjusted to a range of 3.0 to 6.5 using sodium hydroxide and/or hydrochloric acid, if necessary.

Uses and Indications

Phenylephrine Hydrochloride is indicated for increasing blood pressure in adults experiencing clinically important hypotension primarily due to vasodilation. This includes conditions such as septic shock or during anesthesia.

There are no teratogenic or nonteratogenic effects associated with the use of Phenylephrine Hydrochloride.

Dosage and Administration

Prior to administration, the product 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 up to a maximum of 1.4 mcg/kg/minute based on the patient's response.

In patients experiencing vasodilatory shock, a continuous intravenous infusion is indicated at a rate ranging from 0.5 mcg/kg/minute 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 it or any of its components.

Warnings and Precautions

Severe bradycardia and decreased cardiac output have been observed in patients receiving this medication. Healthcare professionals should monitor heart rate and cardiac function closely, particularly in patients 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 for any signs of extravasation.

Caution is advised when this medication is used 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 consider monitoring blood pressure and heart rate during co-administration.

Patients with a known sensitivity to sulfites may experience allergic-type reactions. It is essential to assess patient history for sulfite allergies prior to administration and to monitor for any signs of hypersensitivity during treatment.

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. These reactions are frequently observed in clinical settings and may be particularly prevalent among patients undergoing specific procedures, such as neuraxial anesthesia during cesarean delivery, where nausea and vomiting are often linked to hypotension and bradycardia.

Severe adverse reactions, although less common, can occur and warrant careful monitoring. These include severe bradycardia and decreased cardiac output, which may pose significant risks to patient safety. Additionally, extravasation during intravenous administration has been noted to potentially cause necrosis or sloughing of tissue, emphasizing the importance of proper administration techniques. The concomitant use of this medication with oxytocic drugs may potentiate the pressor effect of sympathomimetic pressor amines, necessitating caution in such combinations.

Allergic-type reactions, particularly hypersensitivity to sulfite or any of the medication's components, have also been reported. Symptoms of overdose may manifest as headache, vomiting, hypertension, reflex bradycardia, and cardiac arrhythmias, including ventricular extrasystoles and ventricular tachycardia. Patients may also report a sensation of fullness in the head and tingling of the extremities.

In summary, while the medication is generally well-tolerated, healthcare providers should remain vigilant for both common and severe adverse reactions, particularly in vulnerable patient populations.

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 several classes of drugs, including 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 of these agents may enhance the pharmacological effects of the medication, potentially leading to increased therapeutic or adverse effects. Clinicians should consider monitoring patients closely for signs of enhanced effects and adjust dosages accordingly.

Conversely, antagonistic interactions may occur with α-adrenergic blocking agents. The presence of these agents may diminish the efficacy of the medication, necessitating careful evaluation of the therapeutic regimen. It is advisable to monitor the clinical response and adjust dosages of the medication as needed to achieve the desired therapeutic outcomes.

Overall, healthcare professionals should exercise caution when prescribing this medication in conjunction with the aforementioned drug classes, ensuring appropriate monitoring and dosage adjustments to mitigate potential interactions.

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

Pediatric patients may be treated with this drug; however, it is not known whether it is excreted in human milk. Healthcare professionals should consider this uncertainty when prescribing to breastfeeding mothers. Further studies may be necessary to establish the safety and efficacy of this drug in specific pediatric populations.

Geriatric Use

There is no specific information regarding the use of this medication in geriatric patients. Therefore, healthcare providers should exercise caution when prescribing this medication to elderly patients. It is advisable to monitor this population closely for any potential adverse effects or changes in efficacy, as age-related physiological changes may influence drug metabolism and response. Additionally, consideration should be given to the presence of comorbidities and concurrent medications that are common in geriatric patients, which may necessitate dosage adjustments or increased monitoring.

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with intravenous phenylephrine. It is not known whether phenylephrine can cause fetal harm when administered to a pregnant woman or affect reproductive capacity. Therefore, phenylephrine hydrochloride should be given to a pregnant woman only if clearly needed. Healthcare professionals are advised to weigh the potential benefits against the risks when considering the use of this medication in pregnant patients.

Lactation

Lactating mothers may experience adverse reactions such as nausea and vomiting when using phenylephrine during neuraxial anesthesia for cesarean delivery. These reactions are often linked to hypotension, bradycardia, reactive hypertension, and transient arrhythmias.

Data suggest that phenylephrine does not significantly affect placental perfusion, as evidenced by stable neonate Apgar scores and blood-gas status. Therefore, the use of phenylephrine in lactating mothers is not expected to adversely impact breastfed infants.

Renal Impairment

There is no specific information available 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 phenylephrine hydrochloride overdose, 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, alongside sensations of fullness in the head and tingling in the extremities.

Management of an overdose should include the consideration of administering an alpha-adrenergic antagonist to mitigate the effects of excessive adrenergic stimulation. Continuous monitoring of the patient's cardiovascular status is essential, and appropriate supportive measures should be implemented as necessary.

Nonclinical Toxicology

Animal reproduction studies have not been conducted with intravenous phenylephrine. The potential for phenylephrine to cause fetal harm when administered to a pregnant woman or to affect reproductive capacity is not known. Therefore, phenylephrine hydrochloride should be administered to a pregnant woman only if clearly needed.

The most common maternal adverse reactions reported in studies of phenylephrine use during neuraxial anesthesia for cesarean delivery include nausea and vomiting, which are frequently associated with hypotension, bradycardia, reactive hypertension, and transient arrhythmias. Phenylephrine does not appear to cause a decrease in placental perfusion sufficient to alter either the neonate Apgar scores or blood-gas status.

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 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 rarely 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 and the risk of skin or tissue damage if the drug leaks from the venous catheter into surrounding tissue. Additional symptoms to discuss include headache, nervousness, tremor, and numbness or tingling (paresthesias) in the hands or feet. Patients may also experience nausea, vomiting, excitability, dizziness, sweating, and flushing.

It is essential for healthcare providers to ensure that patients understand these potential side effects and symptoms, encouraging them to report any concerning changes or reactions during treatment.

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°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F).

To ensure the integrity of the product, it must be protected from light and kept covered in its carton until the time of use. Any unused portion should be discarded 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 Hikma Pharmaceuticals USA Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)