Phentolamine (EENT) (Monograph)

Drug class: EENT Drugs, Miscellaneous

Introduction

Phentolamine is a nonselective alpha adrenergic blocker.

Uses for Phentolamine (EENT)

Phentolamine mesylate has the following uses:

Phentolamine ophthalmic solution is indicated for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents.

Phentolamine (EENT) Dosage and Administration

General

Phentolamine mesylate is available in the following dosage form(s) and strength(s):

Ophthalmic solution containing phentolamine 0.75% in a single-patient-use vial.

Administration

For topical ophthalmic use only.

To avoid eye injury or contamination, avoid touching vial tip to the eye or to any other surface.

Remove contact lenses prior to instillation of the ophthalmic solution and wait 10 minutes after dosing to reinsert the lenses.

Dosage

One single-patient-use vial can be used to dose each dilated eye. Discard the single-patient-use vial immediately after use.

Pediatric Patients

Pediatric patients 3 to 11 years of age: Instill 1 drop in each dilated eye following completion of the ophthalmic examination or procedure.

Pediatric patients 12 years of age and older: Instill 1 or 2 drops in each dilated eye following completion of the ophthalmic examination or procedure. If 2 drops are instilled, the second drop should be administered 5 minutes after the first drop.

Adults

Instill 1 or 2 drops in each dilated eye following completion of the ophthalmic examination or procedure. If 2 drops are instilled, the second drop should be administered 5 minutes after the first drop.

Cautions for Phentolamine (EENT)

Contraindications

None.

Warnings/Precautions

Warnings

Uveitis

Phentolamine ophthalmic solution is not recommended when active ocular inflammation (e.g., iritis) is present because adhesions (synechiae) may form between the iris and the lens.

Potential for Eye Injury or Contamination

To avoid the potential for eye injury or contamination, care should be taken to avoid touching the vial tip to the eye or to any other surface.

Use with Contact Lenses

Contact lens wearers should be advised to remove their lenses prior to the instillation of phentolamine ophthalmic solution and wait 10 minutes after dosing before reinserting their contact lenses.

Specific Populations

Pregnancy

There are no available data with phentolamine ophthalmic solution administration in pregnant women to inform a drug-associated risk. In animal toxicology studies, when phentolamine was administered orally to pregnant mice and rats during the period of organogenesis, skeletal immaturity and decreased growth were observed in the offspring at doses at least 24-times the recommended clinical dose. Additionally, a lower rate of implantation was seen in pregnant rats treated with phentolamine administered at least 60-times the recommended clinical dose. No malformations or embryofetal deaths were observed in the offspring of pregnant mice, rats, and rabbits administered phentolamine during the period of organogenesis at doses of at least 24-, 60-, and 20-times, respectively, the recommended clinical dose. Phentolamine ophthalmic solution should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

Oral administration of phentolamine to pregnant rats and mice at doses at least 24-times the recommended clinical dose (based on a body weight per surface area [mg/m²] comparison with a 60-kg human) resulted in slightly decreased growth and slight skeletal immaturity of the fetuses. Immaturity was manifested by increased incidence of incomplete or unossified calcanei and phalangeal nuclei of the hind limb and of incompletely ossified sternebrae. At oral phentolamine doses at least 60-times the recommended clinical dose (based on a mg/m² comparison with a 60-kg human), a slightly lower rate of implantation was found in rats. Phentolamine did not affect embryonic or fetal development in rabbits at oral doses at least 20-times the recommended dose (based on a mg/m² comparison with a 60-kg human). No malformations or embryofetal deaths were observed in the rat, mouse, or rabbit studies.

Lactation

There is no information regarding the presence of phentolamine in human milk, the effects on the breastfed infants, or the effects on milk production during lactation to inform risk of phentolamine ophthalmic solution to an infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for phentolamine ophthalmic solution and any potential adverse effects on the breastfed child from the drug.

Females and Males of Reproductive Potential

The effect of phentolamine on female fertility has not been studied. Male rats treated with oral phentolamine for nine weeks (four weeks prior to mating, 3 weeks during the mating period and 2 weeks after mating) were mated with untreated females. At doses up to 648-times human therapeutic exposure levels at the Cmax, no adverse effects on male fertility parameters or on reproductive parameters in the untreated females mated with the treated males were observed.

Pediatric Use

The safety and effectiveness of phentolamine ophthalmic solution have been established in pediatric patients 3 to 17 years of age. No overall differences have been observed between pediatric and adult subjects.

Geriatric Use

No overall differences in safety and effectiveness have been observed between elderly and younger adult subjects.

Common Adverse Effects

The most common ocular adverse reactions reported in >5% of subjects were instillation site discomfort including pain, stinging, and burning (16%) and conjunctival hyperemia (12%). The only non-ocular adverse reaction reported in >5% of subjects was dysgeusia (6%).

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailedinformation on interactions with this drug, including possible dosage adjustments.

Actions

Mechanism of Action

Phentolamine is a relatively non-selective alpha-1 and alpha-2 adrenergic antagonist. Dilation of the pupil is primarily controlled by the radial iris dilator muscles surrounding the pupil; these muscles are activated by the alpha-1 adrenergic receptors. Phentolamine reversibly binds to these receptors on the iris dilator muscle, thereby reducing pupil diameter. Phentolamine directly antagonizes the mydriatic effect of an α-1 adrenergic agonist, and indirectly reverses mydriasis induced by muscarinic antagonist effects on the iris sphincter muscle.

Additional Information

AHFSfirstRelease™. For additional information until a moredetailed monograph is developed and published, the manufacturer'slabeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.