Phenylephrine hydrochloride

Description

Phenylephrine hydrochloride is a synthetic sympathomimetic agent formulated for parenteral injection. The chemical designation of phenylephrine hydrochloride is (-)-m-Hydroxy-α-(methylamino)methylbenzyl alcohol hydrochloride, with a structural formula that reflects its molecular composition. 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.

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, as 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.

Limitations of Use: There are no reported teratogenic or nonteratogenic effects associated with 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 the possibility of titration up to 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 a known 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 patients closely for signs of bradycardia and assess cardiac output, particularly in those with pre-existing cardiovascular conditions.

Extravasation during intravenous administration poses a significant 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 for any signs of extravasation to mitigate this risk.

Concomitant use with oxytocic drugs may enhance the pressor effect of sympathomimetic pressor amines. Caution is advised when administering this medication alongside oxytocic agents, and healthcare professionals should consider adjusting dosages or closely monitoring blood pressure and heart rate in these patients.

Allergic-type reactions, particularly those related to sulfite sensitivity, have been reported. Patients with a known history of sulfite allergies should be evaluated carefully prior to administration, and appropriate measures should be taken to manage any potential allergic reactions.

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 typically mild to moderate in severity.

Severe adverse reactions have also been observed. Notably, patients may experience severe bradycardia and decreased cardiac output. Additionally, extravasation during intravenous administration can lead to necrosis or sloughing of tissue. It is important to note that the concomitant use of this medication with oxytocic drugs may potentiate the pressor effect of sympathomimetic pressor amines. Allergic-type reactions, particularly those related to sulfite sensitivity, have been documented as well.

Other adverse reactions of clinical significance include hypersensitivity to the medication or any of its components. Symptoms of overdose may manifest as headache, vomiting, hypertension, reflex bradycardia, and cardiac arrhythmias, which can include ventricular extrasystoles and ventricular tachycardia. Patients may also report a sensation of fullness in the head and tingling of the extremities. Monitoring for these adverse reactions is recommended 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 classes of drugs:

• Monoamine Oxidase Inhibitors (MAOIs): Co-administration may enhance the pharmacological effects, potentially leading to increased risk of hypertensive crises or serotonin syndrome.

• β-Adrenergic Blocking Agents: Concurrent use may amplify the effects on cardiovascular function, necessitating careful monitoring of heart rate and blood pressure.

• α-2 Adrenergic Agonists: The combination may lead to enhanced sedation and hypotensive effects.

• Steroids: There may be an increased risk of side effects related to the immune response and metabolic effects.

• Tricyclic Antidepressants: Co-administration can lead to increased central nervous system effects, including sedation and potential cardiovascular complications.

• Norepinephrine Transport Inhibitors: The interaction may heighten the risk of hypertensive episodes.

• Ergot Alkaloids: Concurrent use may increase the risk of vasospastic reactions.

• Centrally-Acting Sympatholytic Agents: The combination may lead to enhanced central nervous system depression.

• Atropine Sulfate: Co-administration may result in increased anticholinergic effects.

Antagonistic interactions are noted with α-Adrenergic Blocking Agents. The use of these agents may diminish the therapeutic effects of the medication, potentially requiring dosage adjustments or alternative therapies to achieve the desired clinical outcomes.

Healthcare professionals should monitor patients closely for any signs of adverse effects or diminished efficacy when these interactions are present, and consider appropriate dosage adjustments as necessary.

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

Elderly patients may exhibit altered pharmacokinetics and pharmacodynamics, necessitating careful consideration when prescribing medications. It is essential to monitor this population closely for potential adverse effects and therapeutic efficacy.

While specific dosage adjustments for elderly patients are not provided, clinicians should remain vigilant regarding the overall health status and comorbidities that may influence drug metabolism and response.

Furthermore, safety and effectiveness in pediatric patients have not been established, underscoring the importance of tailoring treatment approaches based on age and individual patient characteristics. Regular assessment and monitoring are recommended to ensure optimal outcomes in geriatric patients.

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.

Current 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 appears to be clinically manageable, with no known detrimental effects on breastfed infants.

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 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 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, along with sensations of fullness in the head and tingling in the extremities.

Management of an overdose should include the consideration of administering an α-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. It is not known whether phenylephrine can cause fetal harm when administered to a pregnant woman or if it can affect reproductive capacity. 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 (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, 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. Common symptoms that patients may experience 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. Gastrointestinal symptoms like nausea and vomiting, as well as feelings of excitability, dizziness, sweating, and flushing, should also be discussed.

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 packaging that includes specific NDC numbers. 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). It is essential to protect the product from light and to keep it covered in its carton until it is ready for use.

Once diluted, the solution must not be held at room temperature for more than 4 hours. If refrigerated, the diluted solution should not be stored for more than 24 hours. Any unused portion of the diluted solution should be discarded to ensure 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 Civica, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)