Phenylephrine Hcl (phenylephrine HCl)

To produce decongestion of the conjunctiva, 1 or 2 drops of a 0.12-0.25% ophthalmic solution of phenylephrine hydrochloride may be applied topically to the conjunctiva every 3-4 hours (up to 4 times daily for self-medication) as needed. Vasoconstriction for diagnosis of ocular congestion or to improve visualization of ocular blood vessels in sickle-cell disease may be achieved by application of 1 or 2 drops of a 2.5% solution. In the ''blanching test'', congestion probably is caused by conjunctivitis rather than iridocyclitis if the drug produces perilimbal blanching in the congested eye. A 2.5 or 10% solution of the drug may also be administered prior to surgery to produce mydriasis and aid in controlling hemorrhage. (See Phenylephrine Hydrochloride 52:24.)

To produce nasal decongestion in adults and children 12 years of age or older, the usual dosage is 2 or 3 drops, 1-3 sprays, or 1-3 metered sprays instilled in each nostril. In cases of extreme nasal congestion in adults, a 1% solution may be used initially. To produce nasal decongestion in children 6-12 years of age, 2 or 3 drops or 1 or 2 sprays of a 0.25% solution may be instilled in each nostril. Doses of the drug as drops or spray may be repeated in 4 hours if needed. Phenylephrine nasal solutions should not be used for self-medication for longer than 3 days; if symptoms persist, the drug should be discontinued and a physician consulted. Intranasal application of phenylephrine should generally be used for no longer than 3-5 days.

For use with local anesthetics, phenylephrine hydrochloride may be used in concentrations of 1:2500 to 1:20,000.

Phenylephrine hydrochloride is administered by IV bolus or continuous IV infusion for the treatment of clinically important hypotension. The drug is available as a 10 mg/mL phenylephrine hydrochloride injection concentrate that must be diluted prior to administration and as a ready-to-use phenylephrine hydrochloride 100 mcg/mL (Immphentiv(R), Biorphen(R)) injection. Ready-to-use phenylephrine hydrochloride 100 mcg/mL (Immphentiv(R), Biorphen(R)) injection should not be further diluted before IV bolus administration.

For treatment of hypotension during anesthesia, the manufacturers recommend administration of phenylephrine hydrochloride as an IV bolus or continuous infusion; when used in the treatment of septic shock, the drug should be administered as a continuous IV infusion with no initial bolus dose. Phenylephrine hydrochloride injection should be stored at 20-25degreesC, but may be exposed to temperatures ranging from 15-30degreesC; single-dose and pharmacy bulk vials should be kept in their original carton until time of use and protected from light.

Commercially available phenylephrine hydrochloride injection concentrate must be diluted with a compatible IV solution prior to administration. Diluted solutions may be stored at room temperature for up to 4 hours or under refrigeration for up to 24 hours; any unused portions should be discarded.

Commercially available phenylephrine hydrochloride bulk vials are intended for use in a pharmacy admixture program for preparation of single doses to be dispensed to multiple patients. Each vial should be penetrated only one time with a suitable sterile transfer device or dispensing set. Dispensing from a pharmacy bulk vial should be completed within 4 hours after the vial is penetrated.

Prior to administration, phenylephrine hydrochloride solutions should be inspected visually for particulate matter and discoloration; the drug should be discarded if the solution is colored, cloudy, or contains any particulate matter.

Care should be taken to avoid extravasation and the infusion site should be checked for free flow.

Phenylephrine hydrochloride ophthalmic solutions are applied topically to the conjunctiva. Digital pressure should be applied on the lacrimal sac for 1-2 minutes following topical instillation of ophthalmic solutions to minimize drainage into the nose and throat and reduce the risk of absorption and systemic reactions. Excess solution around the eye should be removed with a tissue.

For intranasal applications, phenylephrine may be administered in solution as drops or spray. Vicks Sinex(R) (with mist spray nozzle) nasal solution is administered by nasal inhalation using a special nasal inhaler that produces metered droplet sprays. Care must be taken to avoid contamination of the dropper, inhaler, or spray. Except in young children in whom sprays are difficult to use, nasal sprays may be preferable to drops because of the lesser risk of swallowing the drug and resultant systemic absorption. Drops should be applied to the dependent (lower) nostril, with the patient in a lateral head-low position. The patient should remain in the same position for 5 minutes, then the solution should be applied to the other nostril in a similar manner. Alternatively, drops may be instilled when the patient is reclining with the head tilted back as far as possible. Sprays should be delivered or pumped (Vicks Sinex(R) metered spray) into each nostril with the patient's head erect so that excess solution is not released. The nose should be blown thoroughly 3-5 minutes later. Prior to initial use of the metered sprays, the nasal inhaler must be primed by depressing the pump firmly several times. To minimize the risk of spreading infections, droppers, inhalers, and spray dispensers should not be used by more than one person, and tips of the dispensers, inhalers, or droppers should be rinsed with hot water following use.

Phenylephrine nasal solutions also may be applied to a tampon or nasal pack for insertion into nasal passages. However, this method of application should be restricted to use in diagnostic or surgical procedures performed under medical supervision because mechanical injury may occur.

No dosing information is available for this tab.

No dosing information is available for this tab.

When applied topically to the conjunctiva (especially in concentrations of 2.5% or greater), phenylephrine hydrochloride must be administered under careful supervision and in reduced dosage if used within 21 days after the patient has received a monoamine oxidase (MAO) inhibitor because potentiation of the pressor effects of phenylephrine may result. Nasal solutions containing phenylephrine must not be given to a patient receiving an MAO inhibitor. The pressor response to phenylephrine may also be potentiated if a tricyclic antidepressant is administered concomitantly.

Concomitant administration of phenylephrine with cycloplegic antimuscarinic drugs such as atropine sulfate, cyclopentolate hydrochloride, homatropine hydrobromide, or scopolamine hydrobromide produces increased mydriatic effects.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Sympathomimetics/Dihydroergotamine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Concurrent use of dihydroergotamine and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels.(1)

CLINICAL EFFECTS: Concurrent use of dihydroergotamine and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Dihydroergotamine is contraindicated with sympathomimetics because the combination may result in additive or synergistic elevation of blood pressure.(1)

DISCUSSION: Significant elevation in blood pressure has been reported in patients treated with dihydroergotamine.(1) Sympathomimetics can be expected to have additional effects on blood pressure.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Agents That Affect Catecholamines/Iobenguane I 123

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Many compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells.(1)

CLINICAL EFFECTS: Compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with imaging completed with iobenguane.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discuss the use of agents that affect catecholamines. Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores prior to imaging with iobenguane. Before imaging with iobenguane, discontinue agents that affect catecholamines for at least 5 biological half-lives, as clinically tolerated.(1)

DISCUSSION: Many agents may reduce catecholamine uptake or deplete catecholamine stores.(1) Examples include: - CNS stimulants or amphetamines (e.g. cocaine, methylphenidate, dextroamphetamine) - norepinephrine and dopamine reuptake inhibitors (e.g. phentermine) - norepinephrine and serotonin reuptake inhibitors (e.g. tramadol) - monoamine oxidase inhibitors (e.g. phenelzine, linezolid) - central monoamine depleting drugs (e.g. reserpine) - non-select beta adrenergic blocking drugs (e.g. labetalol) - alpha agonists or alpha/beta agonists (e.g. pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline) - tricyclic antidepressants or norepinephrine reuptake inhibitors (e.g. amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine) - botanicals that may inhibit reuptake of norepinephrine, serotonin or dopamine (e.g. ephedra, ma huang, St. John's Wort, yohimbine)

Agents That Affect Catecholamines/Iobenguane I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Many compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells.(1)

CLINICAL EFFECTS: Compounds that reduce catecholamine uptake or that deplete catecholamine stores may impact the dosimetry calculations or effectiveness of iobenguane.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discuss the use of agents that affect catecholamines. Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores for at least 5 half-lives before administration of either the dosimetry or a therapeutic dose of iobenguane. Do not administer these drugs until at least 7 days after each iobenguane dose.(1)

DISCUSSION: Many agents may reduce catecholamine uptake or deplete catecholamine stores.(1) Examples include: - CNS stimulants or amphetamines (e.g. cocaine, methylphenidate, dextroamphetamine) - norepinephrine and dopamine reuptake inhibitors (e.g. phentermine) - norepinephrine and serotonin reuptake inhibitors (e.g. tramadol) - monoamine oxidase inhibitors (e.g. phenelzine, linezolid) - central monoamine depleting drugs (e.g. reserpine) - non-select beta adrenergic blocking drugs (e.g. labetalol) - alpha agonists or alpha/beta agonists (e.g. pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline) - tricyclic antidepressants or norepinephrine reuptake inhibitors (e.g. amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine) - botanicals that may inhibit reuptake of norepinephrine, serotonin or dopamine (e.g. ephedra, ma huang, St. John's Wort, yohimbine) - calcium channel blockers

Selected Direct-Acting Sympathomimetics/Tricyclic Compounds

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Unknown. However, it is speculated that direct-acting sympathomimetic amines have an enhanced effect due to tricyclic blockage of norepinephrine reuptake.

CLINICAL EFFECTS: Increased effect of direct acting sympathomimetics.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Consider avoiding the concurrent use of direct-acting sympathomimetics and tricyclic compounds. If concurrent use of direct-acting sympathomimetics and tricyclic compounds is warranted, the initial dose of the sympathomimetic should be lowered and the patient should be monitored for adverse cardiovascular effects. Use of tricyclic compounds and other sympathomimetics should be approached with caution.

DISCUSSION: Epinephrine and other direct-acting sympathomimetic amines exert enhanced cardiovascular effects (e.g., arrhythmias, hypertension, and tachycardia) in individuals concurrently receiving or previously treated with tricyclic antidepressants. Other direct and mixed acting sympathomimetic amines have also been reported to interact with tricyclic antidepressants. These include norepinephrine, phenylephrine, dopamine, and methoxamine. Protriptyline, amitriptyline, and desipramine have also been reported to interact with direct-acting sympathomimetics.

Sympathomimetics/Ergot Alkaloids

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Concurrent use of ergot alkaloids and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels.

CLINICAL EFFECTS: Concurrent use of ergot alkaloids and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: When possible, avoid the concurrent use of ergot alkaloids and sympathomimetics. If concurrent use is warranted, monitor blood pressure and for signs of vasoconstriction. Decreasing the dose of one or both drugs may be necessary.

DISCUSSION: There have been reports of severe vasoconstriction resulting in gangrene in patients receiving intravenous ergonovine with dopamine or norepinephrine.

Sympathomimetics/Selected Inhalation Anesthetic Agents

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The exact mechanism is unknown. The anesthetics produce conduction changes that increase impulse re-entry into the myocardial tissue.(1) The anesthetics' ability to precipitate arrhythmias is enhanced by elevated arterial blood pressure, tachycardia, hypercapnia, and/or hypoxia, events that stimulate the release of endogenous catecholamines.(1)

CLINICAL EFFECTS: Concurrent use of inhalation anesthetic agents and sympathomimetics may result in ventricular arrhythmias or sudden blood pressure and heart rate increase during surgery.(2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor blood pressure and avoid use of sympathomimetics in patients being treated with anesthetics on the day of surgery.(2) Intravenous use of epinephrine during surgery with halothane and related halogenated general anesthetics should be strongly discouraged. When intravenous epinephrine is necessary, nitrous oxide anesthesia supplemented with ether, muscle relaxants, or opioids should be used instead of halothane.(3,4) Epinephrine may safely be used subcutaneously with the following precautions: the patient is adequately ventilated to prevent hypoxia or respiratory acidosis; the total dose of epinephrine is limited to 100 mcg/10 minute period or 300 mcg/hour in adults, 3.5 mcg/Kg in infants, 2.5 mcg/Kg in children up to two years of age, and 1.45 mcg/Kg in children over two years of age; a minimum effective concentration of anesthetic is maintained; the drugs are not co-administered in patients with hypertension or other cardiovascular disorders; and the cardiac rhythm is continuously monitored during and after injection.(3-10) If arrhythmias occur after the administration of the epinephrine, the drugs of choice are lidocaine or propranolol, depending on the type of arrhythmia.(1)

DISCUSSION: Administration of epinephrine during halothane anesthesia may may lead to serious ventricular arrhythmias.(3-6,11-18) This has occurred when epinephrine was administered intravenously,(6) when it was administered with lidocaine as a dental block,(11,14) or when it was administered supraperiosteally.(5) Norepinephrine has been shown to interact with halothane in a manner similar to epinephrine.(1) In two case reports, patients were given terbutaline (0.25 to 0.35 mg) for wheezing following induction of anesthesia with halothane. One patient's heart rate increased from 68 to 100 beats/minute, and the ECG showed premature ventricular contractions and bigeminy, while the other patient developed multiple unifocal premature ventricular contractions and bigeminy. The arrhythmias resolved in both patients following lidocaine administration.(19) Although not documented, isoproterenol causes effects on the heart similar to terbutaline(20) and would probably interact with halothane in a similar manner. Other inhalation anesthetics that increase the incidence of arrhythmias with epinephrine include chloroform,(20) methoxyflurane,(20) and enflurane.(12) A similar interaction may be expected between the other inhalation anesthetics and sympathomimetics.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Sympathomimetics (Direct, Mixed-Acting)/Guanethidine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Direct or mixed-acting sympathomimetics may inhibit uptake of guanethidine at the adrenergic neuron.

CLINICAL EFFECTS: Decreased antihypertensive effectiveness. Effects may be seen for several days after discontinuation of the direct or mixed-acting sympathomimetic.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid concomitant administration of these drugs. If both drugs are administered, adjust the guanethidine dose as needed based on blood pressure.

DISCUSSION: Documentation supports routine monitoring of this interaction. It should be noted that this interaction can occur quickly.

Sympathomimetics (Direct, Mixed-Acting)/Methyldopa

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Unknown.

CLINICAL EFFECTS: The pressor response to sympathomimetics may be increased.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Start with low doses of sympathomimetics and monitor blood pressure of patients during concurrent administration of sympathomimetics and methyldopa.

DISCUSSION: The pressor response to sympathomimetics has been reported to be increased during methyldopa administration. In addition to increased duration of pressor response, severe hypertension has been reported.

Sympathomimetics/Rauwolfia Alkaloids

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Reserpine depletes catecholamine stores within the peripheral vascular adrenergic nerve endings, thus indirect acting sympathomimetics are unable to trigger the release of catecholamines. The reserpine-induced catecholamine release increases sensitivity to the effects of direct acting sympathomimetics.

CLINICAL EFFECTS: Increased effects of direct acting sympathomimetics. Decreased effects of indirect acting sympathomimetics. Mixed acting sympathomimetics will show effects based on the predominance of either direct or indirect activity.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If these agents are administered concurrently, monitor blood pressure. The dose of the sympathomimetic may need to be adjusted.

DISCUSSION: This interaction has been well documented in animal studies and human case reports have confirmed the interaction. Reserpine has been shown to decrease the response to epinephrine administered for hypotension. Reserpine has also been shown to decrease the effectiveness of ophthalmic epinephrine, a direct acting sympathomimetic. Ophthalmic phenylephrine has been shown to decrease the hypotensive effects of reserpine.

*Known hypersensitivity to phenylephrine or to any ingredient in the respective formulation.

There are no contraindication contraindications for this drug.

• Chronic heart failure
• Coronary artery disease
• Peripheral vascular disease
• Pulmonary hypertension
• Severe arteriosclerotic vascular disease

• Acidosis
• Hypoxia

The most commonly reported adverse effects in patients receiving IV phenylephrine hydrochloride were nausea, vomiting, and headache.

Less Frequent

• Bradycardia
• Hypertension
• Tachycardia
• Ventricular arrhythmias

Rare or Very Rare

• Angina
• Extravasation injury
• Hypertensive crisis
• Pulmonary edema
• Tissue necrosis

More Frequent

• Headache disorder
• Nausea
• Vomiting

Less Frequent

• Dizziness
• Dyspnea
• Nervousness
• Pallor
• Palpitations
• Peripheral vasoconstriction
• Symptoms of anxiety
• Tremor

Rare or Very Rare

• Blurred vision
• Neck pain
• Pruritus of skin

No enhanced messaging available.

The manufacturers state that safety and efficacy of parenteral preparations of phenylephrine hydrochloride have not been established in pediatric patients.

Data from randomized trials and meta-analyses with phenylephrine injection in pregnant women undergoing Cesarean section have not established a drug-associated risk of major birth defects or miscarriage. Additionally, the data did not identify adverse effects on maternal outcomes or infant Apgar scores. At recommended doses, phenylephrine does not appear to significantly affect fetal heart rate or fetal heart rate variability. Data are not available on phenylephrine use during the first or second trimester.

Untreated hypotension in pregnant women undergoing Cesarean delivery with neuraxial anesthesia has been associated with increased maternal nausea and vomiting. A sustained decrease in uterine blood flow caused by maternal hypotension has also been associated with fetal bradycardia and acidosis.

No data are available on the safety of phenylephrine injection during the period of organogenesis; therefore, conclusions cannot be drawn regarding the risk of birth defects from drug exposure. In addition, no data are available on the risk of miscarriage following fetal exposure to phenylephrine injection.

In animal studies, fetal malformations were observed following phenylephrine infusion over 1 hour during the period of organogenesis at a dosage of 1.2 times the human daily dosage. Decreased pup weight was also observed in offspring of pregnant rats who received 2.9 times the human daily dose of phenylephrine.

If a vasopressor is used in conjunction with oxytocic drugs, the vasopressor effect is potentiated and may result in serious adverse effects.

Animal reproduction studies have not been performed with phenylephrine. It is not known whether topically applied phenylephrine can cause fetal harm when administered to pregnant women. Parenterally administered phenylephrine in late pregnancy or labor may cause fetal anoxia. (See Cautions: Pregnancy and Lactation, in Phenylephrine Hydrochloride 12:12.04.) Topically applied phenylephrine should be used during pregnancy only when clearly needed.

There are no data on whether phenylephrine or its metabolite is distributed into human or animal milk following parenteral administration. The effects on the breast-fed infant and milk production are not known.

The developmental and health benefits of breast-feeding should be weighed along with the mother's clinical need for the drug and any potential adverse effects on the breast-fed infant from phenylephrine or from the underlying maternal condition.

Since it is not known whether phenylephrine is distributed into milk, the drug should be used with caution in nursing women.

If phenylephrine is used in geriatric patients, dosage should be selected carefully, usually starting at the low end of the dosage range, since renal, hepatic, and cardiovascular dysfunction and concomitant disease or other drug therapy are more common in this age group.

Clinical studies of phenylephrine hydrochloride did not include sufficient numbers of patients >=65 years of age to determine whether geriatric patients respond differently than younger patients. Clinical experience to date has not identified any differences in response between geriatric and younger patients.

If phenylephrine is used in geriatric patients, dosage should be selected carefully, usually starting at the low end of the dosage range, since renal, hepatic, and cardiovascular dysfunction and concomitant disease or other drug therapy are more common in this age group.