Immphentiv, Phenylephrine Hydrochloride

Description

Phenylephrine Hydrochloride Injection and IMMPHENTIV® injection contain phenylephrine as the active pharmaceutical ingredient in the form of hydrochloride salt. Phenylephrine is a synthetic sympathomimetic agent provided in a sterile form suitable for parenteral injection. The chemical name for phenylephrine hydrochloride is (-)-m-Hydroxy-α (methylamino)methylbenzyl alcohol hydrochloride, and it possesses a structural formula that reflects its chemical composition.

Phenylephrine hydrochloride is characterized by its high solubility in water, free solubility in ethanol, and insolubility in chloroform and ethyl ether. It is also sensitive to light. IMMPHENTIV®, USP, is formulated as a clear, colorless, aqueous solution that is essentially free of visible foreign matter and is presented as a Ready-To-Use formulation. Each mL of IMMPHENTIV® contains 100 mcg of Phenylephrine Hydrochloride USP (equivalent to 82 mcg of phenylephrine base), along with 7.5 mg of Sodium Chloride USP as a tonicity agent, 4 mg of Sodium Citrate Dihydrate USP, and 1 mg of Citric Acid Monohydrate USP as buffering agents. Additionally, it includes 0.2 mg of Edetate Disodium USP as a chelating agent, with Sodium Hydroxide NF and Hydrochloric Acid NF used as pH adjusters, all in Water for Injection USP. The pH range for IMMPHENTIV® injection is 3.0 to 6.5.

Phenylephrine Hydrochloride injection, USP, is also a clear, colorless, aqueous solution that is free of visible foreign matter. It must be diluted prior to administration as either a bolus intravenous infusion or a continuous intravenous infusion. Each mL of this formulation contains 10 mg of Phenylephrine Hydrochloride (equivalent to 8.2 mg of phenylephrine base), 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. It also contains 2 mg of Sodium Metabisulfite USP as an antioxidant, with Sodium Hydroxide NF and Hydrochloric Acid NF serving as pH adjusters in Water for Injection. The pH range for Phenylephrine Hydrochloride injection is similarly 3.0 to 6.5.

Uses and Indications

IMMPHENTIV injection 100 mcg/mL is indicated for increasing blood pressure in adults with clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia.

Phenylephrine Hydrochloride Injection 10 mg/mL is also indicated for increasing blood pressure in adults with clinically important hypotension resulting primarily from vasodilation in the settings of anesthesia and septic shock.

There are no teratogenic or nonteratogenic effects associated with these medications.

Dosage and Administration

IMMPHENTIV Injection is administered at a concentration of 100 mcg/mL. It is critical that this product is not diluted prior to administration. For the management of perioperative hypotension, the recommended dosing is an intravenous bolus of 50 mcg to 250 mcg.

Phenylephrine Hydrochloride Injection is available at a concentration of 10 mg/mL and must be diluted before administration. For the treatment of perioperative hypotension, the dosing regimen includes an intravenous bolus of 50 mcg to 250 mcg. Additionally, for continuous infusion, the dosage should be initiated at 0.5 mcg/kg/minute and may be titrated up to 1.4 mcg/kg/minute based on the patient's response.

In cases of vasodilatory shock, Phenylephrine Hydrochloride should be administered as a continuous intravenous infusion, starting at 0.5 mcg/kg/minute and titrated as necessary, with a maximum dose of up to 6 mcg/kg/minute 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.

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 of the medication can lead to serious complications, including 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. Healthcare providers should evaluate the potential risks and benefits of such combinations and monitor patients accordingly.

Allergic-type reactions may occur with Phenylephrine Hydrochloride Injection 10 mg/mL, particularly in individuals with sulfite sensitivity. It is essential to assess patients for any history of sulfite allergies prior to administration and to be prepared to manage any allergic reactions that may arise.

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

Agonistic interactions may occur with several drug classes, 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. Clinicians should be aware of the potential for enhanced effects when these agents are co-administered, which may necessitate careful monitoring of therapeutic outcomes and side effects.

Conversely, antagonistic interactions may arise with α-adrenergic blocking agents. The clinical significance of this interaction should be evaluated, and dosage adjustments may be required based on the patient's response and the specific clinical context. Regular monitoring is advised to ensure optimal therapeutic efficacy and safety.

Packaging & NDC

The table below lists all NDC Code configurations of Immphentiv, Phenylephrine Hydrochloride (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. Monitoring for efficacy and safety is recommended to ensure appropriate therapeutic outcomes in this population.

Pregnancy

In animal reproductive and developmental studies, decreased fetal body weights were observed at 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 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.

Animal reproduction studies have not been conducted with phenylephrine, and it is not known whether phenylephrine can cause fetal harm when administered to a pregnant woman or affect reproductive capacity. Therefore, phenylephrine should be administered to a pregnant woman only if clearly needed. However, the safety of its use for the management of hypotension associated with neuraxial anesthesia in cesarean deliveries is well established.

Lactation

Lactating mothers may receive phenylephrine hydrochloride; however, data on its excretion in human breast milk are not available. In animal studies, no adverse effects on 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 human dose based on body surface area) from Gestation Day 6 to Lactation Day 20. Given the lack of human data, healthcare professionals should weigh the potential benefits against any unknown risks when considering the use of this medication in 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 population to mitigate the risk of adverse effects associated with heightened sensitivity. Monitoring of these patients is essential to ensure appropriate dosing and to adjust as necessary based on clinical response.

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 used in patients without liver dysfunction.

Monitoring of liver function is recommended in these patients to ensure appropriate dosing and to assess any potential adverse effects related to hepatic impairment. Careful evaluation of the patient's clinical status and liver function tests should guide the management and dosing adjustments in this population.

Overdosage

In the event of an overdose of IMMPHENTIV (100 mcg/mL) and phenylephrine hydrochloride injection (10 mg/mL), healthcare professionals should be aware that a rapid increase in blood pressure may occur.

Symptoms of Overdose Patients experiencing an overdose may present with a range of symptoms, including headache, vomiting, and hypertension. Additional manifestations can include 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.

Management Procedures In managing an overdose, it is advisable to consider the administration of an α-adrenergic antagonist to counteract 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

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 and found 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 tested negative 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 the 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 are up to 0.2 times the HDD of 10 mg/60 kg/day based on body surface area, were given 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.

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 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, 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 effects and to encourage them to report any concerning symptoms promptly.

Storage and Handling

The product is supplied in accordance with the following 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) as defined by USP Controlled Room Temperature guidelines. It is essential to protect the product from light and to keep it covered in its carton until it is ready for use.

Any unused portion of the product must be discarded. Additionally, 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 temperatures between 2°C and 8°C.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Immphentiv, 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)