PDR MEMBER LOGIN:

Not a Member? Register Now

Forgot your password?

  • PDR Search

    Required field
  •  
  • Advertisement

  • phenylephrine hydrochloride - Drug Summary

  • CLASSES

    Cardiac Stimulants Excluding Dopaminergic Agents
    Decongestants
    Ocular Decongestants, Sympathomimetics
    Topical Anti-hemorrhoidals
    Topical Nasal Decongestants

    BOXED WARNING

    Requires an experienced clinician

    Phenylephrine injection therapy requires an experienced clinician. The manufacturer includes a black box warning for phenylephrine injection advising that prescribers should become familiar with the product label information before prescribing phenylephrine.

    DEA CLASS

    Rx, OTC

    DESCRIPTION

    Synthetic sympathomimetic amine with selective alpha-1 adrenergic agonist effects
    Used orally and intranasally as decongestant, ophthalmically to produce mydriasis for examination or procedures, and parenterally as a vasopressor
    Adverse reactions due to excessive pharmacologic activity

    COMMON BRAND NAMES

    4-Way Nasal, AK-Dilate, Biorphen, Little Remedies for Noses, Mydfrin, Neo-Synephrine, Neo-Synephrine Cold + Allergy, Neo-Synephrine Extra Strength, Neo-Synephrine Mild, Neofrin, Ocu-Phrin, Sudafed PE, Sudafed PE Children's Nasal Decongestant, Sudafed PE Congestion, Sudafed PE Sinus Congestion, Sudogest PE, Vazculep

    HOW SUPPLIED

    4-Way Nasal/Neo-Synephrine/Neo-Synephrine Cold + Allergy/Neo-Synephrine Extra Strength/Neo-Synephrine Mild Nasal Spray: 0.25%, 0.5%, 1%
    AK-Dilate/Mydfrin/Neofrin/Neo-Synephrine/Ocu-Phrin/Phenylephrine/Phenylephrine Hydrochloride Ophthalmic Sol: 2.5%, 10%
    Biorphen/Phenylephrine/Phenylephrine Hydrochloride/Vazculep Intravenous Inj Sol: 1mL, 10mg, 100mcg
    Little Remedies for Noses Nasal Drops: 0.125%
    Phenylephrine Hydrochloride, Hard fat/Phenylephrine, Hard fat Rectal Supp: 0.25-88.7%
    Phenylephrine/Phenylephrine Hydrochloride/Sudafed PE/Sudafed PE Congestion/Sudafed PE Sinus Congestion/Sudogest PE Oral Tab: 10mg
    Phenylephrine/Phenylephrine Hydrochloride/Vazculep Intramuscular Inj Sol: 1mL, 10mg
    Phenylephrine/Phenylephrine Hydrochloride/Vazculep Subcutaneous Inj Sol: 1mL, 10mg
    Sudafed PE Children's Nasal Decongestant Oral Sol: 2.5mg, 5mL

    DOSAGE & INDICATIONS

    For mydriasis induction before ophthalmic procedures or examination.
    Ophthalmic dosage (10% solution)
    Adults

    1 drop to each eye to be examined, 15 to 30 minutes before the procedure. If needed, the dose may be repeated at 3- to 5-minute intervals to a maximum dose of 3 drops per eye.[54174]

    Children and Adolescents

    1 drop to each eye to be examined, 15 to 30 minutes before the procedure. If needed, the dose may be repeated at 3- to 5-minute intervals to a maximum dose of 3 drops per eye.[54174]

    Ophthalmic dosage (2.5% solution)
    Adults

    1 drop to each eye to be examined, 15 to 30 minutes before the procedure. If needed, the dose may be repeated at 3- to 5-minute intervals to a maximum dose of 3 drops per eye.[54174]

    Infants, Children, and Adolescents

    1 drop to each eye to be examined, 15 to 30 minutes before the procedure. If needed, the dose may be repeated at 3- to 5-minute intervals to a maximum dose of 3 drops per eye.[54174]

    Neonates

    1 drop to each eye to be examined, 15 to 30 minutes before the procedure. If needed, the dose may be repeated at 3- to 5-minute intervals to a maximum dose of 3 drops per eye.[54174]

    For the treatment of paroxysmal supraventricular tachycardia (PSVT).
    Intravenous dosage
    Adults

    The initial dose, given by rapid IV injection, should not exceed 0.5 mg. Subsequent doses, which are determined by the initial blood pressure response, should not exceed the preceding dose by more than 0.1 mg to 0.2 mg. Maximum single dose is 1 mg IV.

    Children† and Adolescents†

    5 to 10 mcg/kg/dose IV over 20 to 30 seconds. Phenylephrine is not a preferred agent for the acute treatment of PSVT in pediatric patients and is not a standard drug used in pediatric advanced life support (PALS) protocols.

    For the treatment of hypotension or shock.
    For mild to moderate hypotension.
    Intramuscular or Subcutaneous dosage
    Adults

    2 to 5 mg IM or subcutaneously (range: 1 to 10 mg) every 10 to 15 minutes as needed. Max initial dose: 5 mg.

    Children† and Adolescents†


    0.1 mg/kg/dose (Max: 5 mg/dose) IM or subcutaneously every 1 to 2 hours as needed.

    Intravenous dosage
    Adults

    0.1 to 0.5 mg IV every 10 to 15 minutes as needed. Usual dose: 0.2 mg.

    For severe hypotension or shock (e.g., drug-induced severe hypotension, septic shock†, traumatic brain injury (TBI)).
    Intravenous dosage
    Adults

    0.5 mcg/kg/minute continuous IV infusion, initially. Titrate every 30 minutes to blood pressure goal up to 6 mcg/kg/minute. Doses more than 6 mcg/kg/minute do not offer significant increase in blood pressure. Alternately, 100 to 180 mcg/minute continuous IV infusion until the blood pressure stabilizes, with dosage titration to the desired mean arterial pressure (MAP) and systemic vascular resistance (SVR). The usual maintenance infusion rate is 40 to 60 mcg/minute IV. Patients with hypovolemia should receive adequate fluid resuscitation prior to administration of phenylephrine. Phenylephrine is not recommended as first-line therapy for septic shock. Infusion rates up to 360 mcg/minute IV have been reported to maintain MAP during severe septic shock.

    Infants†, Children†, and Adolescents†

    5 to 20 mcg/kg IV, then 0.1 to 0.5 mcg/kg/minute continuous IV infusion, initially; titrate to hemodynamic goals.[32485] [54587] [54588] Although the maximum dosage has not been established, infusion rates up to 3 mcg/kg/minute IV have been reported.[32481] [32482] Other vasopressors are generally preferred for pediatric advanced life support (PALS), but phenylephrine may be useful for select emergent circumstances.[43713] [54587] [54588]

    For the treatment of clinically important hypotension primarily from vasodilation in the setting of anesthesia.
    Intravenous dosage
    Adults

    40 to 100 mcg IV every 1 to 2 minutes as needed to maintain target blood pressure. Max total dose: 200 mcg.[57578] [64705] If blood pressure is below target goal, start 10 to 35 mcg/minute continuous IV infusion, not to exceed 200 mcg/minute.[57578]

    For the treatment of clinically important hypotension in the perioperative setting with neuraxial or general anesthesia.
    Intravenous dosage
    Adults

    50 to 250 mcg IV. Usual dose: 50 or 100 mcg. If needed, start 0.5 mcg/kg/minute continuous IV infusion and titrate to blood pressure goal up to Max: 1.4 mcg/kg/minute.

    For use during spinal anesthesia.
    For prevention of hypotension during spinal anesthesia.
    Subcutaneous or Intramuscular dosage
    Adults

    2 to 3 mg subcutaneously or IM, 3 to 4 minutes before spinal anesthesia. A dose of 2 mg subcutaneously or IM is usually adequate with lower levels of spinal anesthesia; however, 3 mg IM or subcutaneously may be necessary with higher levels of spinal anesthesia.

    Children and Adolescents

    0.044 to 0.088 mg/kg/dose IM or subcutaneously.

    For the prolongation of spinal anesthesia.
    Intraspinal dosage
    Adults

    2 to 5 mg added to the anesthetic solution increases the duration of motor block by as much as 50% without an increase in the incidence of complications such as nausea, vomiting, or blood pressure disturbances.

    For hypotensive emergencies during spinal anesthesia.
    Intravenous dosage
    Adults

    0.2 mg IV initially. Subsequent doses should not exceed the previous dose by more than 0.1 to 0.2 mg. Maximum: 0.5 mg/dose IV. Infusions have also been used with dosing similar to that used for other hypotensive states to prevent or treat hypotension. High phenylephrine IV infusion rates have been reported for some patient populations including spinal anesthesia induced hypotension, including during cesarean delivery.

    For vasoconstriction for regional anesthesia.
    Parenteral dosage
    Adults

    1 mg added to each 20 mL of local anesthetic solution; optimum concentration is 0.05 mg/mL. Some pressor response can be expected when at least 2 mg is injected.[32480]

    For the treatment of sinus and nasal congestion and eustachian tube congestion due to the common cold, allergic rhinitis, or sinusitis.
    Oral dosage
    Adults

    10 to 20 mg PO every 4 to 6 hours as needed. Max: 60 mg/day. Initiate dosage at the lower end of the adult dosage range for geriatric patients; the dose may be increased if needed. Elderly patients are more likely to have adverse reactions.

    Children and Adolescents 12 to 17 years

    10 to 20 mg PO every 4 to 6 hours as needed. Max: 60 mg/day.

    Children 6 to 11 years

    5 mg PO every 4 to 6 hours as needed. Max: 30 mg/day.

    Children 4 to 5 years

    2.5 mg PO every 4 to 6 hours as needed. Max: 15 mg/day. Nonprescription use is not recommended in this patient population due to reports of serious adverse effects; use under the advice of a health care professional.

    Intranasal dosage (1% nasal drops or 0.5% and 1% nasal spray)
    Adults

    2 to 3 sprays or drops to each nostril every 4 hours as needed. Use beyond 3 days is not recommended.

    Children and Adolescents 12 to 17 years

    2 to 3 sprays or drops to each nostril every 4 hours as needed. Use beyond 3 days is not recommended.[54370]

    Intranasal dosage (0.25% nasal spray)
    Adults

    2 to 3 sprays to each nostril every 4 hours as needed. Use beyond 3 days is not recommended.

    Children and Adolescents 6 to 17 years

    2 to 3 sprays to each nostril every 4 hours as needed. Use beyond 3 days is not recommended.

    Intranasal dosage (0.125% nasal drops)
    Children 2 to 5 years

    2 to 3 drops to each nostril every 4 hours as needed. Use beyond 3 days is not recommended.

    For the treatment of internal and external symptoms of hemorrhoids.
    Topical dosage (rectal cream or ointment)
    Adults

    Apply to the affected area 4 times daily, especially at night, in the morning, or after each bowel movement.[54364]

    Children and Adolescents 12 to 17 years

    Apply to the affected area 4 times daily, especially at night, in the morning, or after each bowel movement.[54364]

    Rectal dosage (suppository)
    Adults

    1 suppository/dose rectally up to 4 times daily, usually in the morning, evening, or after each bowel movement.[54363]

    Children and Adolescents 12 to 17 years

    1 suppository/dose rectally up to 4 times daily, usually in the morning, evening, or after each bowel movement.[54363]

    For the treatment of epistaxis†.
    Nasal dosage
    Adults

    2 to 6 sprays in the affected nostril(s) during the active bleed, then 2 sprays 3 to 4 times daily for 3 to 5 days. Alternatively, soak gauze or a cotton pledget in the decongestant solution and place in the affected nostril(s) for 30 minutes.[65040]

    For the treatment of hypercyanotic episodes associated with tetralogy of fallot (i.e., tetralogy spells†).
    Intravenous dosage
    Infants and Children

    5 to 20 mcg/kg/dose IV once, followed by 0.1 to 5 mcg/kg/minute continuous IV infusion.

    Neonates

    5 to 20 mcg/kg/dose IV once, followed by 0.1 to 5 mcg/kg/minute continuous IV infusion.

    †Indicates off-label use

    MAXIMUM DOSAGE

    NOTE: For certain indications and routes of administration, phenylephrine dosage must be individualized and is highly variable depending on the nature and severity of the disease and on patient response; do not exceed recommended dosage limits for the specific product prescribed; the following are general guidelines:

    Adults

    60 mg/day PO; 3 sprays/drops of 1% nasal solution to each nostril within a 4-hour period; 1 drop/dose of 2.5% or 10% ophthalmic solution per eye; 4 applications/day of hemorrhoidal cream/ointment; 4 suppositories/day PR. For parenteral use, the maximum dose is dependent on condition being treated.

    Geriatric

    60 mg/day PO; 3 sprays/drops of 1% nasal solution to each nostril within a 4-hour period; 1 drop/dose of 2.5% or 10% ophthalmic solution per eye; 4 applications/day of hemorrhoidal cream/ointment; 4 suppositories/day PR. For parenteral use, the maximum dose is dependent on condition being treated.

    Adolescents

    60 mg/day PO; 3 sprays/drops of 1% nasal solution to each nostril within a 4-hour period; 1 drop/dose of 2.5% or 10% ophthalmic solution per eye; 4 applications/day of hemorrhoidal cream/ointment; 4 suppositories/day PR. For parenteral use, the maximum dose is dependent on condition being treated.

    Children

    12 years: 60 mg/day PO; 3 sprays/drops of 0.5% or 1% nasal solution to each nostril within a 4-hour period; 1 drop/dose of 2.5% or 10% ophthalmic solution per eye; 4 applications/day of hemorrhoidal cream/ointment; 4 suppositories/day PR. For parenteral use, the maximum dose is dependent on condition being treated.
    6 to 11 years: 30 mg/day PO; 3 sprays of 0.25% nasal solution to each nostril within a 4-hour period; 1 drop/dose of 2.5% or 10% ophthalmic solution per eye. For parenteral use, the maximum dose is dependent on condition being treated.
    4 to 5 years: 15 mg/day PO; 3 drops of 0.125% nasal solution in each nostril within a 4-hour period; 1 drop/dose of 2.5% or 10% ophthalmic solution per eye. For parenteral use, the maximum dose is dependent on condition being treated.
    2 to 3 years: 15 mg/day PO has been used off-label; 3 drops of 0.125% nasal solution in each nostril within a 4-hour period; 1 drop/dose of 2.5% or 10% ophthalmic solution per eye. For parenteral use, the maximum dose is dependent on condition being treated.
    1 to 2 years: PO and intranasal administration not recommended; 1 drop/dose of 2.5% or 10% ophthalmic solution per eye. For parenteral use, the maximum dose is dependent on condition being treated.

    Infants

    PO and intranasal administration not recommended; 1 drop/dose of 2.5% ophthalmic solution per eye; safety and efficacy of injectable solution not established.

    Neonates

    PO and intranasal administration not recommended; 1 drop/dose of 2.5% ophthalmic solution per eye; safety and efficacy of injectable solution not established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Patients with Child-Pugh Class B or C hepatic impairment may experience decreased responsiveness to phenylephrine, and more phenylephrine may be needed in this population; initiate treatment in the recommended range, and adjust dose based on the target blood pressure goal.[54374] [57578] [64705]

    Renal Impairment

    Patients with end-stage renal disease (ESRD) may experience increased responsiveness to phenylephrine, and less phenylephrine may be needed in this population; initiate treatment at the lower end of the recommended range, and adjust dose based on the target blood pressure goal.[54374] [57578] [64705]

    ADMINISTRATION

    Oral Administration

    May be administered without regard to meals.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.[54374]
    Updates for coronavirus disease 2019 (COVID-19): The FDA is allowing phenylephrine 0.1 mg/mL, 10 mg/mL, 50 mg/5 mL, and 100 mg/10 mL to be used beyond the labeled in-use time to help ensure access during COVID-related drug shortages. This period should be as short as possible, and for a maximum of 2 hours at room temperature or 4 hours when refrigerated. In-use time is defined as the maximum amount of time allowed to elapse between penetration of a closed-container system or after reconstitution of a lyophilized drug before patient administration.[65833]

    Intravenous Administration

    Pharmacy Bulk Vial (Vazculep)
    Bulk vials are intended for dispensing single doses of admixtures for infusion to multiple patients in a pharmacy admixture process.
    Each closure should be penetrated only 1 time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents.
    Complete dispensing from a bulk vial within 4 hours after the vial is penetrated.[57578]
     
    Ready-to-Use Formulation (Biorphen)
    Do not dilute before administration.[64705]
     
    IV Push
    Concentrated products require dilution; admix 1 mL of the 10 mg/mL solution with 99 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection for a final concentration of phenylephrine 100 mcg/mL.
    Inject appropriate dose directly into a large vein over 20 to 30 seconds.[54374]
     
    Continuous IV Infusion
    Solution concentration and administration rate are dependent on the patient's drug and fluid requirements and intravenous access. Central line access is preferred.[54374]
    Reassess vital signs with each dose change during titration.
    Use infusion pump for administration.
    Standard usual concentrations:
    FDA-approved labeling recommends phenylephrine 10 mg/500 mL (i.e., 20 mcg/mL) in 0.9% Sodium Chloride Injection or 5% Dextrose Injection.[54374] [57578]
    ASHP Recommended Standard Concentrations for Adult Continuous Infusions: 80 mcg/mL or 400 mcg/mL (for severe fluid restriction in those with high dosing requirements).[64020]
    For pediatric (PICU) and neonatal intensive care (NICU), some institutions have reported the use of standard phenylephrine infusion concentrations of 50 mcg/mL and 100 mcg/mL for "smart-pump" infusion.[54599]
     
    Extravasation Management
    Do not inject phenylephrine into extremities such as fingers, toes, nose, and genitalia because it can cause severe tissue necrosis due to vasoconstriction of small blood vessels.
    If extravasation of phenylephrine occurs, infiltrate the affected area as soon as possible with 10 to 15 mL of normal saline solution containing 5 to 10 mg phentolamine for adults; use a syringe with a fine hypodermic needle to liberally infiltrate throughout the ischemic area.
    The ischemic area may be identified by a cool, hard, and pallid appearance. Phentolamine causes immediate and noticeable local hyperemic changes if the area is infiltrated within 12 hours of extravasation.[53946] [54374]

    Intramuscular Administration

    No dilution necessary.
    Inject deeply into a large muscle.

    Subcutaneous Administration

    Inject subcutaneously taking care not to inject intradermally.

    Inhalation Administration
    Intranasal Inhalation Administration

    Instruct patient on the proper technique for administering the nasal solution or drops.
    To avoid the spread of infection, do not use the container for more than one person.

    Rectal Administration

    Rectal Cream or Ointment
    Cleanse the area before use. Remove the protective cover from the applicator tip, attach the applicator tip to the medication tube, and lubricate the applicator. Insert the applicator tip into the rectum and squeeze the tube to apply a small amount of medication. After use, cleanse the applicator tip and replace cover. Apply some medication to the external area.
     
    Rectal Suppository
    Cleanse the area before use.
    Instruct patient or caregiver on proper use of suppository.
    Prior to insertion, carefully remove the wrapper. Avoid excessive handling as to avoid melting of the suppository.
    If suppository is too soft to insert, chill in the refrigerator for 30 minutes or run cold water over it before removing the wrapper.
    Moisten the suppository with cool water prior to insertion.
    Have patient lie down on their side, usually in the Sim's lateral position to provide support and comfort.
    Apply gentle pressure to insert the suppository completely into the rectum, pointed end first, using a gloved, lubricated index finger.
    After insertion, keep the patient lying down to aid retention.

    Ophthalmic Administration

    Instruct the patient on proper instillation of eye solution.
    Do not touch the tip of the dropper to the eye, fingertips, or other surface.
    Apply pressure to the lacrimal sac for 2 to 3 minutes after instillation to avoid increased systemic absorption.
    To avoid the spread of infection, do not use the container for more than 1 person.
    Do not use if the solution is brown or contains a precipitate.[54169]

    STORAGE

    Generic:
    - Protect from light
    - Store between 68 to 77 degrees F
    - Store in outer carton when not in use
    4-Way Nasal:
    - Store between 68 to 77 degrees F
    AK-Dilate:
    - Avoid excessive heat (above 104 degrees F)
    - Avoid extreme temperatures
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Keep away from heat and flame
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Anu-Med:
    - Store below 86 degrees F
    Biorphen:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - See package insert for detailed storage information
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in carton until time of use
    Formulation R :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Hemorrhoidal :
    - Store below 86 degrees F
    Little Remedies for Noses:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Lusonal:
    - Store at room temperature (between 59 to 86 degrees F)
    Mydfrin:
    - Avoid excessive heat (above 104 degrees F)
    - Avoid extreme temperatures
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Keep away from heat and flame
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Nasop:
    - Store at room temperature (between 59 to 86 degrees F)
    Nasop 12:
    - Store at room temperature (between 59 to 86 degrees F)
    Neofrin:
    - Avoid excessive heat (above 104 degrees F)
    - Avoid extreme temperatures
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Keep away from heat and flame
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Neo-Synephrine:
    - Avoid excessive heat (above 104 degrees F)
    - Avoid extreme temperatures
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Keep away from heat and flame
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Neo-Synephrine Cold + Allergy:
    - Store between 68 to 77 degrees F
    Neo-Synephrine Extra Strength:
    - Store between 68 to 77 degrees F
    Neo-Synephrine Mild:
    - Store between 68 to 77 degrees F
    Ocu-Phrin:
    - Avoid excessive heat (above 104 degrees F)
    - Avoid extreme temperatures
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Keep away from heat and flame
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    PediaCare Children's Decongestant:
    - Storage information not listed
    PediaCare Decongestant:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    PediaCare Infants' Decongestant:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Sinex Nasal:
    - Store at room temperature (between 59 to 86 degrees F)
    Sudafed PE:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Sudafed PE Children's Nasal Decongestant :
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Sudafed PE Congestion:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Sudafed PE Sinus Congestion:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Sudogest PE:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Vazculep:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - Reconstituted product maintains potency for 4 hours at room temperature or for 24 hours under refrigeration (41 degrees F)
    - Store at 20 to 25 degrees C (68 to 77 degrees F); excursions permitted between 15 to 30 degrees C (59 to 86 degrees F) USP Controlled Room Temperature
    - Store diluted product in accordance with package insert instructions
    - Store in a cool, well ventilated, dry place
    - Store in carton until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    Requires an experienced clinician

    Phenylephrine injection therapy requires an experienced clinician. The manufacturer includes a black box warning for phenylephrine injection advising that prescribers should become familiar with the product label information before prescribing phenylephrine.

    MAOI therapy

    Systemic phenylephrine should not be combined with MAOI therapy or used within 2 weeks of such therapy; use caution with ophthalmic, nasal, and topical rectal products, which may be absorbed systemically.

    Angina, arteriosclerosis, cardiac disease, heart failure, hypertension, peripheral vascular disease, pulmonary hypertension, ventricular tachycardia

    Some formulations of injectable phenylephrine are contraindicated in patients with severe hypertension or ventricular tachycardia.[32480] Because of its increasing blood pressure effects, phenylephrine can cause severe bradycardia and decrease cardiac output, precipitate angina in patients with severe arteriosclerosis or a history of angina, and exacerbate underlying heart failure or pulmonary hypertension. Excessive peripheral and visceral vasoconstriction and ischemia to vital organs may occur, especially in patients with significant peripheral vascular disease.[32480] [54374] [57578] [64705] The phenylephrine 10% ophthalmic solution is contraindicated in patients with hypertension; use the 2.5% solution in patients with hypertension or preexisting cardiac disease.[54174] In addition, use orally or nasally administered phenylephrine with caution in patients with known or suspected cardiac disease or high blood pressure.[54354] [54370]

    Aneurysm, cerebrovascular disease, intracranial bleeding, organic brain syndrome, stroke

    Phenylephrine should be avoided in patients with cerebrovascular disease such as cerebral arteriosclerosis, aneurysm, intracranial bleeding, history or stroke or organic brain syndrome because of the potential sympathomimetic (presumably alpha) effects in the CNS and the potential for cerebrovascular hemorrhage, especially with intravenous use.

    Sulfite hypersensitivity

    Avoid phenylephrine in patients with sulfite hypersensitivity unless the patient is being treated for an emergent condition such as anaphylaxis or cardiac arrest. Phenylephrine formulations contain sodium metabisulfite, a sulfite that can cause severe allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes in susceptible patients. The overall presence of sulfite hypersensitivity in the general population is unknown but presumed to be low. Sulfite hypersensitivity is seen most often in asthmatic patients compared to non-asthmatic patients.[32480] [54374] [57578]

    Prostatic hypertrophy, urinary retention

    Systemic phenylephrine products should be used with caution in men with symptomatic, benign prostatic hypertrophy, due to the potential for urinary retention.

    Hyperthyroidism, thyrotoxicosis

    The phenylephrine 10% ophthalmic solution is contraindicated in patients with thyrotoxicosis, including hyperthyroidism; the 2.5% solution should be used with caution in these patients. All dosage forms of phenylephrine should be used with caution in patients with hyperthyroidism as these patients can be more sensitive to catecholamines; thyrotoxic or cardiotoxic symptoms can occur.

    Diabetes mellitus

    Because phenylephrine is an adrenergic agent, it should be given with caution to patients with diabetes mellitus.

    Extravasation

    Avoid extravasation of phenylephrine injection by checking infusion site for free flow. Extravasation of phenylephrine can cause necrosis and tissue sloughing.[54374] [64705]

    Children, infants, neonates

    The 10% ophthalmic phenylephrine solution is contraindicated in neonates and infants younger than 1 year due to the potential for adverse cardiac effects. Infants and children are more susceptible than adults to systemic absorption from intranasal or ophthalmic use, especially with use of the 10% ophthalmic solution, increasing the risk of adverse events. Consider avoiding the use of the 10% solution in patients younger than 5 years. The adverse effects of systemically absorbed sympathomimetics, such as phenylephrine, can be severe, especially in infants and toddlers; CNS stimulation, hypertension and tachycardia may occur.[26649] Do not use oral nonprescription phenylephrine products in children and infants younger than 4 years; use any systemic decongestant sympathomimetic amine with caution in children 6 years and younger.[54360] Administration of cough and cold products to children and infants younger than 2 years is associated with a risk for serious injury or fatal overdose.  Over a 2-year period, 1,519 children younger than 2 years were treated in emergency departments for adverse events related to cough and cold medications; some of these events were due to inadvertent inappropriate use and some fatalities occurred.[33534] Nonprescription cough and cold products containing phenylephrine are not recommended for use in children younger than 6 years. Over-the-counter cough and cold products are not recommended for use in infants and children younger than 2 years. Advise parents and caregivers to read labels carefully, to use caution when administering multiple products, and to use only measuring devices specifically designed for use with medications if using cough and cold products in children. Thoroughly assess each patient's use of similar products, both prescription and nonprescription, to avoid duplication of therapy and the potential for inadvertent overdose.[41013] [41014]

    Labor, obstetric delivery, pregnancy

    There are no data on the use of phenylephrine injection during the first or second trimester of human pregnancy. Data from randomized controlled trials and meta-analyses with phenylephrine injection use in pregnant women during labor and obstetric delivery (i.e., Cesarean section) have not established a drug-associated risk of major birth defects and miscarriage. These studies have not identified an adverse effect on maternal outcomes of infant Apgar scores. At recommended doses, phenylephrine does not appear to affect fetal heart rate or fetal heart rate variability to a significant degree. Untreated hypotension associated with spinal anesthesia for Cesarean section is associated with an increase in maternal nausea and vomiting. A sustained decrease in uterine blood flow due to maternal hypotension may result in fetal bradycardia and acidosis. In animal studies, evidence of fetal malformation was noted when phenylephrine was administered during organogenesis via a 1-hour infusion at 1.2 times the human daily dose (HDD) of 10 mg/60 kg/day. Decreased pup weights were noted in the offspring of pregnant rats treated with 2.9 times the HDD.[57578] Decreased fetal body weights with no clear treatment-related malformations were reported in a study of normotensive pregnant rabbits treated with a single daily intravenous phenylephrine bolus dose of 40 mcg, 100 mcg, and 200 mcg/kg (0.08, 0.2 and 0.4 times the HDD based on body surface area) from gestation days 7 to 19. An increased incidence of agenesis of the intermediate lobe of the lung was also noted in all treatment groups compared to controls. A study in rabbits indicated that continued moderate overexposure to oral phenylephrine (3 mg/day) during the second half of pregnancy may contribute to perinatal wastage, prematurity, premature labor, and possibly fetal anomalies; when phenylephrine (3 mg/day) was given to rabbits during the first half of pregnancy, a significant number gave birth to litters of low birth weight. Another study showed that phenylephrine was associated with anomalies of aortic arch and with ventricular septal defect in the chick embryo.[49510] It is not known whether phenylephrine ophthalmic solution can cause fetal harm or affect reproduction capacity. Use phenylephrine ophthalmic solution during pregnancy only if clearly needed.[54169] Under the direction of a health care professional, topical or nasal phenylephrine may be used during pregnancy.[54363] [54364] [54370]

    Breast-feeding

    There are no data on the presence of phenylephrine or its metabolite in human or animal milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for phenylephrine and any potential adverse effects on the breast-fed infant from phenylephrine or from the underlying maternal condition.[49510] [57578] Use caution when administering ophthalmic phenylephrine to a pregnant woman.[54169] Under the direction of a health care professional, topical or nasal phenylephrine may be used by a breast-feeding woman.[54363] [54364] [54370]

    Contact lenses

    The ophthalmic use of phenylephrine while wearing contact lenses is not recommended.

    Ocular surgery

    Ophthalmic application of phenylephrine to eyes or adnexa that are diseased, traumatized or following ocular surgery, or to patients with suppressed lacrimation (e.g., during anesthesia) may result in sufficient absorption of phenylephrine to produce a systemic vasopressor effect.

    Geriatric

    In general, use caution in administering phenylephrine to geriatric patients. In general, elderly patients are more susceptible than younger adults to the drug's effects. The baroreceptor reflex response to phenylephrine may decrease with age. Elderly patients, especially those with pre-existing cardiac disease, may be more likely to experience adverse cardiovascular reactions including increased blood pressure, cardiac arrhythmias, or ischemia with systemic use. Phenylephrine, when administered by ophthalmic routes, should be also used with caution. The use of the 2.5% ophthalmic solution is preferred for elderly patients when using ophthalmic formulas; avoid use of the 10% ophthalmic solution. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to the OBRA guidelines, use of cough, cold, and allergy medications should be limited to less than 14 days unless there is documented evidence of enduring symptoms that cannot otherwise be alleviated and for which a cause cannot be identified and corrected. OBRA guidelines also state that oral decongestants, such as phenylephrine, should be used cautiously in patients who have insomnia or hypertension. Oral decongestants may cause dizziness, nervousness, insomnia, palpitations, urinary retention, and elevated blood pressure. During use of phenylephrine to manage urinary incontinence, assessment of the underlying causes and identification of the type/category of urinary incontinence needs to be documented prior to or soon after initiating treatment. Medications for urinary incontinence have specific and limited indications based on the cause and categorization of incontinence. Patients should be assessed periodically for medication effects on urinary incontinence as well as lower urinary tract symptoms and treatment tolerability.

    Phenylketonuria

    Some oral chewable formulations of phenylephrine contain aspartame and such products should be avoided or restricted in patients who have phenylketonuria or who must restrict intake of phenylalanine, an amino acid used in the synthesis of aspartame.

    Cyclopropane anesthesia, halothane anesthesia

    Phenylephrine injection should be used cautiously during cyclopropane anesthesia or halothane anesthesia since these agents may sensitize the heart to the arrhythmic action of phenylephrine.

    Shock

    Monitor renal function closely in patients with septic shock; phenylephrine can increase the need for renal replacement therapy.

    Hepatic disease

    Dose-response data indicate decreased responsiveness to injectable phenylephrine in patients with cirrhosis or hepatic disease (Child-Pugh Class B and C). Initiate treatment in the recommended range; more phenylephrine may be required in this population.[54374] [57578] [64705]

    Renal failure

    Dose-response data indicate increased responsiveness to injectable phenylephrine in patients with end-stage renal disease (ESRD) or renal failure. Consider initiating treatment at the lower end of the recommended dosage range, and adjust the dose based on the target blood pressure goal.[54374] [57578] [64705]

    Autonomic neuropathy

    Use phenylephrine with caution in patients with autonomic neuropathy. Patients with autonomic dysfunction, such as those with spinal cord injury, may have an increased blood pressure response to adrenergic drugs.[54374] [57578] [64705]

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / Incidence not known
    AV block / Early / Incidence not known
    heart failure / Delayed / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    intracranial bleeding / Delayed / Incidence not known
    tissue necrosis / Early / Incidence not known
    visual impairment / Early / Incidence not known
    bowel ischemia / Delayed / Incidence not known
    pulmonary edema / Early / Incidence not known

    Moderate

    sinus tachycardia / Rapid / Incidence not known
    hypertension / Early / Incidence not known
    angina / Early / Incidence not known
    blurred vision / Early / Incidence not known
    photophobia / Early / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    contact dermatitis / Delayed / Incidence not known
    excitability / Early / Incidence not known
    colitis / Delayed / Incidence not known
    dyspnea / Early / Incidence not known

    Mild

    nausea / Early / 1.0-10.0
    headache / Early / Incidence not known
    restlessness / Early / Incidence not known
    syncope / Early / Incidence not known
    diaphoresis / Early / Incidence not known
    injection site reaction / Rapid / Incidence not known
    pallor / Early / Incidence not known
    skin discoloration / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    nasal irritation / Early / Incidence not known
    rhinitis / Early / Incidence not known
    nasal congestion / Early / Incidence not known
    ocular pain / Early / Incidence not known
    mydriasis / Early / Incidence not known
    tremor / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known
    vomiting / Early / Incidence not known
    abdominal pain / Early / Incidence not known

    DRUG INTERACTIONS

    Acarbose: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Acebutolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Acetaminophen; Caffeine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Acetaminophen; Caffeine; Pyrilamine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Acetaminophen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Aclidinium; Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Acrivastine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Albiglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Albuterol: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Alogliptin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Alogliptin; Pioglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Alpha-blockers: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Alpha-glucosidase Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Alprazolam: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Ambrisentan: (Major) Sympathomimetics can antagonize the effects of vasodilators when administered concomitantly. Patients should be monitored for reduced efficacy if taking ambrisentan with a sympathomimetic.
    Amiloride: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Amiodarone: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Amlodipine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Amlodipine; Atorvastatin: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Amlodipine; Benazepril: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Amlodipine; Celecoxib: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Amlodipine; Olmesartan: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Amlodipine; Valsartan: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Amoxapine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
    Angiotensin II receptor antagonists: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Angiotensin-converting enzyme inhibitors: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin-converting enzyme inhibitors. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Arformoterol: (Moderate) Caution and close observation should be used when arformoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Aspirin, ASA; Caffeine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Atenolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Atenolol; Chlorthalidone: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Atomoxetine: (Moderate) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
    Atropine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Atropine; Difenoxin: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Atropine; Edrophonium: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Avanafil: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
    Azelastine; Fluticasone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Azilsartan; Chlorthalidone: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Beclomethasone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Bendroflumethiazide; Nadolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Benzodiazepines: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Beta-blockers: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Betamethasone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Betaxolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Bethanechol: (Moderate) Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects.
    Bisoprolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Bretylium: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
    Brimonidine; Timolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Bromocriptine: (Moderate) The combination of bromocriptine with phenylephrine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phenylephrine should be approached with caution. One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm.
    Brompheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Budesonide: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Budesonide; Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Bumetanide: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Butalbital; Acetaminophen; Caffeine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Butorphanol: (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
    Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Caffeine; Sodium Benzoate: (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Calcium-channel blockers: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Canagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Canagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Carbinoxamine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Cardiac glycosides: (Moderate) Carefully monitor patients receiving cardiac glycosides and vasopressors concurrently due to the increased risk of arrhythmia.
    Carteolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Carvedilol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Cetirizine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Chlordiazepoxide: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Chlordiazepoxide; Amitriptyline: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Chlordiazepoxide; Clidinium: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Chlorothiazide: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Chlorpheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Chlorthalidone: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Chlorthalidone; Clonidine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Ciclesonide: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Clevidipine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Clonazepam: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Clonidine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
    Clorazepate: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Cocaine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration.
    Codeine; Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Colchicine: (Minor) The response to sympathomimetics may be enhanced by colchicine.
    Corticosteroids: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Cortisone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Dapagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dapagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dapagliflozin; Saxagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Deflazacort: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Desloratadine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Desmopressin: (Moderate) Although the pressor activity of desmopressin is very low compared to its antidiuretic activity, large doses of desmopressin should be used with other pressor agents like phenylephrine only with careful patient monitoring.
    Dexamethasone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Dexbrompheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Diazepam: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Diethylpropion: (Major) Diethylpropion has vasopressor effects. Coadministration with other vasopressors may have the potential for serious cardiac adverse effects such as hypertensive crisis and cardiac arrhythmias.
    Digitoxin: (Moderate) Carefully monitor patients receiving cardiac glycosides and vasopressors concurrently due to the increased risk of arrhythmia.
    Digoxin: (Moderate) Carefully monitor patients receiving cardiac glycosides and vasopressors concurrently due to the increased risk of arrhythmia.
    Dihydroergotamine: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Diltiazem: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Diphenoxylate; Atropine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Dopamine: (Moderate) Monitor blood pressure during concomitant use of dopamine and other vasopressors, such as phenylephrine, due to the risk for severe hypertension.
    Dorzolamide; Timolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Doxazosin: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Dronabinol: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
    Dulaglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Dyphylline: (Moderate) Use of sympathomimetics with dyphylline should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias.
    Dyphylline; Guaifenesin: (Moderate) Use of sympathomimetics with dyphylline should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias.
    Empagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Empagliflozin; Linagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Empagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Epoprostenol: (Major) Avoid use of sympathomimetic agents with epoprostenol. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including epoprostenol. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Ergoloid Mesylates: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Ergonovine: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Ergot alkaloids: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Ergotamine: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Ergotamine; Caffeine: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension. (Moderate) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine should be avoided or used cautiously. Excessive caffeine ingestion (via medicines, supplements or beverages including coffee, green tea, other teas, guarana, colas) may contribute to side effects like nervousness, irritability, insomnia, or tremor.
    Ertugliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Ertugliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Ertugliflozin; Sitagliptin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Esmolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Estazolam: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Ethacrynic Acid: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Exenatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Felodipine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Fentanyl: (Major) Pain control may be impaired if fentanyl nasal spray is administered in patients receiving vasoconstrictive nasal decongestants (e.g., phenylephrine); do not titrate fentanyl nasal spray dose in such patients. This interaction is not expected with other fentanyl administration routes.
    Fexofenadine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Finasteride; Tadalafil: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
    Fludrocortisone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Flunisolide: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Flurazepam: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Fluticasone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Fluticasone; Salmeterol: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Fluticasone; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Formoterol; Mometasone: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Furosemide: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Glimepiride; Rosiglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Glipizide; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Glyburide; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Glycopyrrolate; Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Green Tea: (Moderate) Some, but not all, green tea products contain caffeine. Caffeine should be avoided or used cautiously with phenylephrine. CNS stimulants and sympathomimetics are associated with adverse effects such as nervousness, irritability, insomnia, and cardiac arrhythmias.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Guanabenz: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of guanabenz when administered concomitantly. Patients should be monitored for loss of blood pressure control.
    Haloperidol: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Hydrocodone; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Hydrocortisone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Ibuprofen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Iloprost: (Major) Avoid use of sympathomimetic agents with iloprost. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including iloprost. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Incretin Mimetics: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Indacaterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Indacaterol; Glycopyrrolate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Indapamide: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Insulin Degludec; Liraglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Insulin Glargine; Lixisenatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Insulins: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Iobenguane I 123: (Major) Discontinue medications that decrease norepinephrine uptake, such as phenylephrine, for at least 5 biological half-lives prior to iobenguane I 123 administration. Consider medication tapering or additional supportive therapy as appropriate to minimize the risk for precipitating phenylephrine withdrawal symptoms. Medications that decrease the uptake of norepinephrine can cause false negative imaging results. Increasing the dose of iobenguane I 123 will not overcome any potential uptake limiting effect of this medication.
    Iobenguane I 131: (Major) Discontinue sympathomimetics for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart sympathomimetics until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as sympathomimetics, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
    Ionic Contrast Media: (Major) The intravascular injection of a contrast medium should never be made after the administration of vasopressors since they strongly potentiate neurologic effects. Serious neurologic sequelae, including permanent paralysis, have been reported after cerebral arteriography, selective spinal arteriography, and arteriography of vessels supplying the spinal cord.
    Ipratropium; Albuterol: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Isocarboxazid: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Isoflurane: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension.
    Isradipine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Ketamine: (Moderate) Closely monitor vital signs when ketamine and phenylephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Phenylephrine may enhance the sympathomimetic effects of ketamine.
    Labetalol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Levalbuterol: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Levamlodipine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Levobetaxolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Levobunolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Levothyroxine: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
    Levothyroxine; Liothyronine (Porcine): (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
    Levothyroxine; Liothyronine (Synthetic): (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
    Linagliptin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Linezolid: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Liothyronine: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
    Liraglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Lixisenatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Loop diuretics: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Loratadine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Lorazepam: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Losartan; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Loxapine: (Moderate) Patients taking loxapine can have reduced pressor response to phenylephrine.
    Macitentan: (Major) Avoid use of sympathomimetic agents with macitentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including macitentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Maprotiline: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
    Mecamylamine: (Major) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by mecamylamine. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Meglitinides: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Metaproterenol: (Major) Caution and close observation should also be used when metaproterenol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Metformin; Repaglinide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Metformin; Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Metformin; Saxagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Metformin; Sitagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Methyclothiazide: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Methyldopa: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
    Methylergonovine: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Methylphenidate Derivatives: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
    Methylprednisolone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Metolazone: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Metoprolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Midazolam: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Midodrine: (Major) Midodrine stimulates alpha-adrenergic receptors. Coadministration of midodrine with other vasoconstrictive agents, such as phenylephrine, may enhance or potentiate the effects of midodrine.
    Miglitol: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Mometasone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Monoamine oxidase inhibitors: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Nabilone: (Moderate) Concurrent use of nabilone with sympathomimetics (e.g., amphetamine or cocaine) may result in additive hypertension, tachycardia, and possibly cardiotoxicity. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, 0 to 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases reaching a plateau at 50 bpm.
    Nadolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Nafarelin: (Moderate) If use of a topical nasal decongestants (e.g., oxymetazoline, tetrahydrozoline, phenylephrine nasal) is necessary during therapy with intranasal nafarelin, the decongestant should not be used for at least 2 hours after nafarelin is administered.
    Naproxen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Nebivolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Nebivolol; Valsartan: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Nicardipine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Nicotine: (Minor) Vasoconstricting nasal decongestants such as oxymetazoline, phenylephrine, pseudoephedrine, and tetrahydrozoline prolong the time to peak effect of nasally administered nicotine (i.e., nicotine nasal spray); however, no dosage adjustments are recommended.
    Nifedipine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Nimodipine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Nisoldipine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Nitrates: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
    Non-Ionic Contrast Media: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Olopatadine; Mometasone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Oxazepam: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Oxytocin: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Ozanimod: (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
    Penbutolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Perindopril; Amlodipine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Phendimetrazine: (Major) Phendimetrazine is a phenylalkaline sympathomimetic agent. All sympathomimetics and psychostimulants, including other anorexiants, should be used cautiously or avoided in patients receiving phendimetrazine. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmia.
    Phenelzine: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Phenothiazines: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Phenoxybenzamine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Phentermine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias.
    Phentermine; Topiramate: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias.
    Phentolamine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Phosphodiesterase inhibitors: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
    Pindolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Pioglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Pioglitazone; Glimepiride: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Pioglitazone; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Potassium-sparing diuretics: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Pramlintide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Prazosin: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Prednisolone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Prednisone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Probenecid; Colchicine: (Minor) The response to sympathomimetics may be enhanced by colchicine.
    Procarbazine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Propofol: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Propranolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Pseudoephedrine; Triprolidine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Quazepam: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Racepinephrine: (Major) Racepinephrine is a sympathomimetic drug with agonist actions at both the alpha and beta receptors. Patients using racepinephrine inhalation are advised to avoid other non-prescription products containing sympathomimetics since additive adverse effects on the cardiovascular and nervous system are possible, some which may be undesirable. Side effects such as nausea, tremor, nervousness, difficulty with sleep, and increased heart rate or blood pressure may be additive. Patients should avoid use of non-prescription decongestants, such as phenylephrine and pseudoephedrine, while using racepinephrine inhalations. Patients should avoid dietary supplements containing ingredients that are reported or claimed to have a stimulant or weight-loss effect, such as ephedrine and ephedra, Ma huang, and phenylpropanolamine.
    Rasagiline: (Moderate) The concomitant use of rasagiline and sympathomimetics was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and sympathomimetics including stimulants for ADHD and weight loss, non-prescription nasal, oral, and ophthalmic decongestants, and weight loss dietary supplements containing Ephedra. Although sympathomimetics are contraindicated for use with other non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. One case of elevated blood pressure has been reported in a patient during concurrent use of the recommended dose of rasagiline and ophthalmic tetrahydrozoline. One case of hypertensive crisis has been reported in a patient taking the recommended dose of another MAO-B inhibitor, selegiline, in combination with ephedrine. It should be noted that the MAO-B selectivity of rasagiline decreases in a dose-related manner as increases are made above the recommended daily dose and interactions with sympathomimetics may be more likely to occur at these higher doses.
    Remimazolam: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Riociguat: (Major) Avoid use of sympathomimetic agents with riociguat. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including riociguat. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Rosiglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Safinamide: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phenylephrine. If concomitant use of safinamide and phenylephrine is necessary, monitor for hypertension and hypertensive crisis.
    Salmeterol: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.
    Selegiline: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Selexipag: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Semaglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Sevoflurane: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension.
    SGLT2 Inhibitors: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Sibutramine: (Major) Concurrent use of sibutramine with other serotonergic agents may increase the potential for serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Sildenafil: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
    Solriamfetol: (Moderate) Monitor blood pressure and heart rate during coadministration of solriamfetol, a norepinephrine and dopamine reuptake inhibitor, and vasopressors. Concurrent use of solriamfetol and other medications that increase blood pressure and/or heart rate may increase the risk of such effects. Coadministration of solriamfetol with other drugs that increase blood pressure or heart rate has not been evaluated.
    Sotalol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Spironolactone: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    St. John's Wort, Hypericum perforatum: (Major) St. John's wort may have MAOI-like activities, and could potentially increase the cardiac stimulation and vasopressor effects of the sympathomimetics. St. John's wort should be used cautiously with any sympathomimetic agent.
    Sulfonylureas: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Tadalafil: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
    Telmisartan; Amlodipine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Temazepam: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Terazosin: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Terbutaline: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Theophylline, Aminophylline: (Moderate) Concurrent administration of theophylline or aminophylline with some sympathomimetics can produce excessive stimulation and effects such as nervousness, irritability, or insomnia. Seizures or cardiac arrhythmias are also possible. (Moderate) Concurrent administration of theophylline or aminophylline with sympathomimetics can produce excessive stimulation manifested by skeletal muscle activity, agitation, and hyperactivity.
    Thiazide diuretics: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Thiazolidinediones: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Thiothixene: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Thyroid hormones: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
    Timolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
    Tirzepatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
    Torsemide: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Trandolapril; Verapamil: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Tranylcypromine: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Treprostinil: (Major) Avoid use of sympathomimetic agents with treprostinil. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including treprostinil. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
    Triamcinolone: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Triamterene: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Triazolam: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. Monitor patients for decreased pressor effect if these agents are administered concomitantly.
    Tricyclic antidepressants: (Major) Tricyclic antidepressants (TCAs) may markedly enhance the pressor response to parenteral direct-acting sympathomimetic agents such as norepinephrine and, to a lesser extent, epinephrine and phenylephrine. TCAs inhibit norepinephrine reuptake in adrenergic neurons, resulting in increased stimulation of adrenergic receptors. Clinically, the patient might experience hypertension, headache, tremor, palpitations, chest pain, or irregular heartbeat.
    Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
    Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Vardenafil: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
    Vasodilators: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present.
    Verapamil: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no data on the use of phenylephrine injection during the first or second trimester of human pregnancy. Data from randomized controlled trials and meta-analyses with phenylephrine injection use in pregnant women during labor and obstetric delivery (i.e., Cesarean section) have not established a drug-associated risk of major birth defects and miscarriage. These studies have not identified an adverse effect on maternal outcomes of infant Apgar scores. At recommended doses, phenylephrine does not appear to affect fetal heart rate or fetal heart rate variability to a significant degree. Untreated hypotension associated with spinal anesthesia for Cesarean section is associated with an increase in maternal nausea and vomiting. A sustained decrease in uterine blood flow due to maternal hypotension may result in fetal bradycardia and acidosis. In animal studies, evidence of fetal malformation was noted when phenylephrine was administered during organogenesis via a 1-hour infusion at 1.2 times the human daily dose (HDD) of 10 mg/60 kg/day. Decreased pup weights were noted in the offspring of pregnant rats treated with 2.9 times the HDD.[57578] Decreased fetal body weights with no clear treatment-related malformations were reported in a study of normotensive pregnant rabbits treated with a single daily intravenous phenylephrine bolus dose of 40 mcg, 100 mcg, and 200 mcg/kg (0.08, 0.2 and 0.4 times the HDD based on body surface area) from gestation days 7 to 19. An increased incidence of agenesis of the intermediate lobe of the lung was also noted in all treatment groups compared to controls. A study in rabbits indicated that continued moderate overexposure to oral phenylephrine (3 mg/day) during the second half of pregnancy may contribute to perinatal wastage, prematurity, premature labor, and possibly fetal anomalies; when phenylephrine (3 mg/day) was given to rabbits during the first half of pregnancy, a significant number gave birth to litters of low birth weight. Another study showed that phenylephrine was associated with anomalies of aortic arch and with ventricular septal defect in the chick embryo.[49510] It is not known whether phenylephrine ophthalmic solution can cause fetal harm or affect reproduction capacity. Use phenylephrine ophthalmic solution during pregnancy only if clearly needed.[54169] Under the direction of a health care professional, topical or nasal phenylephrine may be used during pregnancy.[54363] [54364] [54370]

    MECHANISM OF ACTION

    Phenylephrine is a potent vasoconstrictor. It possesses both direct and indirect sympathomimetic effects. Phenylephrine is used parenterally to achieve cardiovascular effects. The dominant effect is agonism at alpha-adrenergic receptors (direct effect). In therapeutic doses, the drug has no substantial stimulant effect on the beta-adrenergic receptors of the heart (beta-1 adrenergic receptors), although activation of these receptors can occur when very large doses are given. Phenylephrine does not stimulate beta-adrenergic receptors of the bronchi or peripheral blood vessels (beta-2 adrenergic receptors). It is believed that alpha-adrenergic effects result from inhibition of cyclic adenosine-3',5'-monophosphate (cAMP) production through inhibition of the enzyme adenyl cyclase, whereas beta-adrenergic effects result from stimulation of adenyl cyclase activity. Phenylephrine also releases norepinephrine from its nerve terminal storage sites (indirect effect). Some investigators have reported that tachyphylaxis can develop. Phenylephrine lacks direct inotropic and chronotropic effects on the heart. The main effect of systemic doses is vasoconstriction, resulting in constriction of most vascular beds including renal, splanchnic, and pulmonary blood vessels. Pulmonary vascular resistance may increase and a slight reduction in cardiac output may occur. Reflex bradycardia may occur, which can be reversed by atropine.[32480]
     
    Phenylephrine may be used to treat paroxysmal supraventricular tachycardia based on its effects to reduce heart rate as a reflex mechanism in response to its alpha1-agonist vasoconstrictive effects.[32480]
     
    A dose-ranging study in septic shock patients, escalating doses ranging from 0.5 to 8 mcg/kg/minute IV at 30-minute intervals, has reported linear dose-related increases in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI).[32495] Although phenylephrine has been reported to increase cardiac output in septic patients based on limited data, cardiac output may be reduced in some patients, presumably due to increased systemic vascular resistance and potential for reflex bradycardia.[32358] [32480] [32495] Phenylephrine substantially reduces splanchnic blood flow in septic shock patients.
     
    Phenylephrine is used orally and intranasally to stimulate alpha-adrenergic receptors on the nasal mucosa (direct effect) causing vasoconstriction of local vessels. The vasoconstrictive action decreases mucosal edema, thereby leading to a decongestant effect.[54373]
     
    Within the eye, phenylephrine also stimulates alpha-adrenergic receptors (direct effect). Stimulation of these receptors on the dilator muscle and arterioles of the conjunctiva leads to profound mydriasis and vasoconstriction, respectively.[54174]

    PHARMACOKINETICS

    Phenylephrine is administered orally, intranasally, ophthalmically, intravenously, intramuscularly, subcutaneously, and rectally.[32480] [54174] [54354] [54364] [54367] The pharmacologic effects of phenylephrine are terminated at least partially by uptake of the drug into tissues. The volume of distribution at steady-state ranges from 184 to 543 L, suggesting high distribution into organs and peripheral tissues. Phenylephrine is primarily metabolized in the liver and intestine by monoamine oxidase (MAO) and sulfotransferase. The major metabolite, m-hydroxymandelic acid, accounts for 57% of the total administered dose.[54374] [64705] Only 16% of the drug is excreted in the urine unchanged with IV administration, and 2.6% after oral administration. The average total serum clearance is approximately 2,100 mL/minute. The elimination half-life ranges between 2.1 to 3.4 hours after oral or IV administration.[26172] [64705]
     
    Affected cytochrome P450 isoenzymes and drug transporters: none

    Oral Route

    When administered orally, phenylephrine is completely absorbed. The drug has a bioavailability of 38% relative to IV administration. Peak plasma concentrations are achieved approximately 1 to 2 hours after administration.[26172] Onset of action can occur in 15 to 30 minutes.[54376]

    Intravenous Route

    After IV administration, a pressor effect occurs almost immediately and persists for 15 to 20 minutes.[54374] With IV infusion, phenylephrine displays biexponential decline; the half-life of the alpha phase is approximately 5 minutes.[26172]

    Intramuscular Route

    After IM administration, a pressor effect occurs within 10 to 15 minutes and persists for 30 minutes to 2 hours.[32480] [54377]

    Subcutaneous Route

    After subcutaneous administration, a pressor effect occurs within 10 to 15 minutes and persists for 50 minutes to 1 hour.

    Inhalation Route

    The duration of action after intranasal administration ranges from 30 minutes to 4 hours.

    Other Route(s)

    Ophthalmic Route
    Maximum plasma concentrations occur 20 minutes after administration with maximal mydriasis in 20 to 90 minutes.[54174] [54375] The duration of the mydriatic effect is roughly 3 hours after administration of the 2.5% solution; the duration may be as long as 7 hours after administration of the 10% solution. Systemic absorption is more likely to be significant with 10% solution use; nasolacrimal occlusion after dosing may limit systemic effects and is recommended.[54169]