APRACLONIDINE HYDROCHLORIDE
Clinical safety rating: safe
CNS depressants may enhance sedative effects Abrupt discontinuation can cause rebound hypertension and nervousness.
Alpha-2 adrenergic receptor agonist; reduces intraocular pressure by decreasing aqueous humor production and increasing uveoscleral outflow.
| Metabolism | Primarily excreted unchanged in urine; minimal hepatic metabolism via unknown pathways. |
| Excretion | Renal excretion: approximately 40% unchanged; hepatic metabolism (CYP2D6) with biliary/fecal elimination of metabolites; total clearance 0.15 L/h/kg. |
| Half-life | Terminal elimination half-life is 8.0-12.0 hours (mean 10 h) in normal renal function; prolonged to up to 40 hours in severe renal impairment. |
| Protein binding | Approximately 40% bound to plasma proteins (albumin). |
| Volume of Distribution | Vd is 1.5-2.0 L/kg; suggests extensive extravascular distribution. |
| Bioavailability | Ophthalmic: systemic absorption is low (≈1%); oral bioavailability is ~70% but not clinically used. |
| Onset of Action | Ophthalmic: IOP reduction begins within 1 hour; peak effect at 3-5 hours. |
| Duration of Action | Ophthalmic: IOP reduction persists for up to 12 hours; clinical use requires twice-daily dosing. |
1-2 drops of 0.5% or 1% solution in the affected eye(s) three times daily.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | No dose adjustment required, but monitor for adverse effects in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | No specific recommendations; use with caution in severe hepatic impairment (Child-Pugh class C) due to risk of encephalopathy. |
| Pediatric use | Safety and effectiveness have not been established; limited data suggest 0.5% solution 1 drop three times daily for pediatric glaucoma (off-label). |
| Geriatric use | No specific dose adjustment; monitor for hypotension, bradycardia, and dry mouth due to increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects Abrupt discontinuation can cause rebound hypertension and nervousness.
| FDA category | Animal |
| Breastfeeding | Apraclonidine is excreted in human milk. M/P ratio not reported. Due to limited data and potential for serious adverse reactions in nursing infants (e.g., bradycardia, hypotension, drowsiness), caution is advised. Use only if clearly needed and monitor infant for sedation, bradycardia, and respiratory depression. Consider pumping and discarding milk for 4-6 hours after topical dose to minimize exposure. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | ADHD |
| Serious Effects |
["Hypersensitivity to apraclonidine or any component","Use with monoamine oxidase inhibitors (MAOIs)","Use in patients receiving systemic clonidine or other alpha-2 agonists","Severe cardiovascular disease (e.g., unstable angina, heart failure)","Concomitant use with drugs that potentiate bradycardia or hypotension"]
| Precautions | ["Severe cardiovascular disease including recent myocardial infarction, cerebrovascular disease, orthostatic hypotension, syncope","Depression","Bradycardia","Hypotension","Raynaud's phenomenon","Renal impairment","Use with caution in patients with history of severe coronary insufficiency"] |
| Food/Dietary | None known. No dietary restrictions are required with ophthalmic apraclonidine use. |
Loading safety data…
| Apraclonidine hydrochloride is an alpha-2 adrenergic agonist. No adequate and well-controlled studies in pregnant women. In animal studies, no evidence of fetal harm at doses up to 4 mg/kg/day (rabbit) and 5 mg/kg/day (rat). Potential for decreased placental perfusion due to alpha-2 agonism. First trimester: Risk cannot be ruled out; use only if clearly needed. Second and third trimesters: May cause fetal bradycardia, hypotension, or hypoxia from systemic absorption; prolonged use near term may contribute to neonatal hypotension, bradycardia, or respiratory depression. |
| Fetal Monitoring | Maternal: Monitor blood pressure and heart rate due to potential for systemic effects (hypotension, bradycardia). Monitor for signs of corneal toxicity with prolonged use. Fetal/neonatal: If used near term, monitor neonatal heart rate, blood pressure, and respiratory status for first 24-48 hours. Consider fetal heart rate monitoring during labor if systemic absorption is suspected. |
| Fertility Effects | No specific human studies on fertility. Animal studies: No evidence of impaired fertility in rats at oral doses up to 5 mg/kg/day. Potential for reversible reduction in libido or erectile dysfunction in males due to alpha-2 agonism. In females, no known direct effect on ovulation or conception. |
| Clinical Pearls | Apraclonidine is used to control intraocular pressure (IOP) in patients on maximally tolerated medical therapy. Due to its alpha-2 agonist activity, it can cause systemic hypotension and bradycardia in susceptible patients. Monitor IOP and vital signs. Tachyphylaxis (loss of effect) can occur with prolonged use. Contraindicated in patients with severe cardiovascular disease or those taking monoamine oxidase inhibitors (MAOIs). Use with caution in patients with depression, Raynaud's phenomenon, or orthostatic hypotension. Local adverse effects include conjunctival blanching, lid retraction, and mydriasis. Apraclonidine may interfere with the diagnosis of Horner syndrome by causing pharmacologic mydriasis. |
| Patient Advice | This medication is used to lower pressure in the eye; do not touch the dropper tip to any surface to avoid contamination. · Apply pressure to the inner corner of the eye (nasolacrimal occlusion) for 1 minute after instillation to reduce systemic absorption. · Do not wear contact lenses during treatment; wait at least 15 minutes after instillation before inserting lenses. · Report symptoms of slow heartbeat, fainting, or severe dizziness to your doctor immediately. · May cause drowsiness or blurred vision; avoid driving or operating machinery until you know how this medication affects you. · If you miss a dose, use it as soon as possible unless it is almost time for the next dose; do not double the dose. · Store at room temperature away from light and moisture; discard any unused solution after the expiration date. |