IHEEZO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IHEEZO (IHEEZO).
Iheezo (phentolamine ophthalmic solution) is an alpha-adrenergic antagonist that inhibits sympathetic tone to the iris dilator muscle, preventing mydriasis and facilitating pupil constriction during ocular surgery.
| Metabolism | Systemic absorption is negligible; metabolism, if any, is likely via hepatic enzymes similar to systemic phentolamine (minimal data for ophthalmic formulation). |
| Excretion | IHEEZO (proparacaine) is predominantly metabolized by plasma esterases; less than 5% is excreted unchanged in urine. Biliary/fecal elimination is negligible. |
| Half-life | The terminal elimination half-life of proparacaine is approximately 1-2 minutes due to rapid hydrolysis by plasma esterases, resulting in a very short duration of systemic exposure. |
| Protein binding | Proparacaine is approximately 75% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | The volume of distribution of proparacaine is not well characterized due to rapid metabolism; estimated Vd is low (<1 L/kg) reflecting limited tissue distribution. |
| Bioavailability | Ophthalmic: Systemic bioavailability is negligible due to rapid local hydrolysis and small administered dose. Oral bioavailability is not applicable due to extensive first-pass metabolism. |
| Onset of Action | Ophthalmic: Anesthetic effect occurs within 20-30 seconds after instillation. |
| Duration of Action | Ophthalmic: Anesthesia lasts approximately 15-20 minutes, sufficient for short procedures; prolonged use may cause corneal toxicity. |
| Molecular Weight | 392.46 Da |
1 drop in the affected eye(s) 3 times daily as needed for relief of ocular discomfort. For optimal use, administer at least 10 minutes apart from other ophthalmic medications.
| Dosage form | GEL |
| Renal impairment | Not required; IHEEZO undergoes minimal systemic absorption and renal impairment does not affect its ocular efficacy or safety. |
| Liver impairment | Not required; hepatic impairment does not alter the pharmacokinetics of IHEEZO due to negligible systemic absorption. |
| Pediatric use | 1 drop in the affected eye(s) up to 3 times daily as needed for children aged 3 years and older. Safety and efficacy in children under 3 years have not been established. |
| Geriatric use | No dose adjustment necessary; elderly patients may use the standard adult dose. Caution in those with severe dry eye syndrome or concurrent ocular conditions. |
| 1st trimester | No adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to fetus. |
| 2nd trimester | No adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to fetus. |
| 3rd trimester | No adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to fetus. |
Clinical note
Comprehensive clinical and safety monograph for IHEEZO (IHEEZO).
| Placental transfer | Not studied; expected to cross placenta due to low molecular weight. |
| Breastfeeding | Not known whether IHEEZO is excreted in human milk. Caution should be exercised when administered to a nursing woman. |
| Lactation Rating |
■ FDA Black Box Warning
No boxed warning.
| Serious Effects |
Hypersensitivity to IHEEZO or any of its excipients
| Precautions | Avoid use in patients with narrow-angle glaucoma or anatomically narrow angles due to risk of angle closure., Do not administer concurrently with other alpha-adrenergic antagonists or drugs that may cause miosis, as additive effects may occur., Use with caution in patients with a history of iritis or uveitis, as pupil constriction may be incomplete. |
| Food/Dietary | No clinically significant food interactions reported. Avoid excessive alcohol consumption as it may potentiate hypotensive effects. |
| Clinical Pearls |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | IHEEZO (apraclonidine ophthalmic) is not systemically absorbed in significant amounts. No fetal risks have been identified from clinical use; however, no well-controlled studies in pregnant women exist. Animal studies show no teratogenic effects at doses far exceeding ophthalmic exposure. FDA Pregnancy Category C. First trimester: theoretical risk minimal. Second and third trimesters: no known fetal adverse effects. |
| Fetal Monitoring | No specific monitoring required beyond standard ophthalmic follow-up. Monitor for maternal systemic adverse effects (e.g., bradycardia, hypotension) if excessive dosing or accidental ingestion occurs. |
| Fertility Effects | No known effects on fertility based on available data. Ophthalmic use with minimal systemic absorption is unlikely to impact reproductive function. |
| IHEEZO (apraclonidine ophthalmic solution) 1% is a selective alpha-2 adrenergic agonist indicated for the control of intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. It is also used off-label for Horner syndrome diagnosis via the apraclonidine test. Onset of IOP reduction occurs within 1 hour, with peak effect at 2-4 hours. Its effect on IOP is adjunctive or mono-therapy, but it may lose efficacy over time (tachyphylaxis). Contraindicated in patients with severe cardiovascular disease, sulfite allergy, or concomitant MAOI use. Monitor for dry mouth, fatigue, and allergic conjunctivitis. Use with caution in patients with depression, Raynaud's, or orthostatic hypotension. |
| Patient Advice | Instill one drop in the affected eye(s) three times daily, about 8 hours apart. · Wash hands before and after use. Do not touch the dropper tip to any surface. · Wait at least 5 minutes between instilling other eye medications. · Remove contact lenses before use and wait at least 15 minutes before reinserting. · May cause blurred vision; avoid driving or operating machinery if affected. · Report any signs of eye redness, swelling, itching, or discharge. · May cause dry mouth, fatigue, or dizziness; avoid alcohol. · Do not use if solution changes color or becomes cloudy. |