ACULAR PRESERVATIVE FREE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACULAR PRESERVATIVE FREE (ACULAR PRESERVATIVE FREE).
Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, thereby reducing prostaglandin synthesis. It produces anti-inflammatory and analgesic effects.
| Metabolism | Ketorolac undergoes hepatic metabolism via hydroxylation and conjugation (glucuronidation) to inactive metabolites. It is primarily metabolized by CYP2D6 and CYP3A4 isoenzymes, with renal excretion of metabolites and unchanged drug. |
| Excretion | Primarily renal excretion of metabolites and unchanged drug; approximately 80% of a dose is excreted in urine as ketorolac and its hydroxy metabolites, with about 6% excreted in feces. |
| Half-life | Terminal elimination half-life is approximately 5-6 hours in adults, but can be prolonged in elderly patients (up to 8-9 hours) and in patients with renal impairment (up to 13-19 hours). |
| Protein binding | 99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.15-0.25 L/kg after oral administration; for ophthalmic use, systemic absorption is minimal, so Vd is not clinically meaningful. |
| Bioavailability | Ophthalmic administration: Systemic bioavailability is approximately 0.5-1% after ocular instillation due to low corneal penetration and rapid clearance; oral bioavailability is 100%. |
| Onset of Action | Ocular administration: Onset of action occurs within 30 minutes to 1 hour; peak effect is seen at 2-3 hours. |
| Duration of Action | Duration of action for ocular use is approximately 4-6 hours after a single dose; however, clinical efficacy for inflammation reduction may persist for up to 12 hours with continuous dosing. |
1 drop into affected eye(s) four times daily (every 6 hours). Instill into conjunctival sac. Shake well before use.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | No dosage adjustment required for renal impairment. Drug is minimally absorbed systemically. |
| Liver impairment | No dosage adjustment required for hepatic impairment. Drug is minimally absorbed systemically. |
| Pediatric use | Children ≥3 years: 1 drop into affected eye(s) four times daily. Safety and efficacy in children <3 years not established. |
| Geriatric use | No specific dosage adjustment required. Use same dose as adults; monitor for tolerability. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACULAR PRESERVATIVE FREE (ACULAR PRESERVATIVE FREE).
| Breastfeeding | Ketorolac is excreted in human milk following oral administration. After a single intramuscular dose of 10 mg, the milk-to-plasma (M/P) ratio was 0.037. Low levels are expected in breastmilk; however, due to potential adverse effects of NSAIDs on neonates, caution is advised. Use is generally avoided in nursing mothers, especially with premature infants or those with thrombocytopenia or renal impairment. |
| Teratogenic Risk | FDA Pregnancy Category C. No adequate studies in pregnant women. In animal studies, ketorolac tromethamine (active ingredient) was not teratogenic in rats or rabbits at doses up to 1.5-3 times the human exposure. However, because NSAIDs can cause premature closure of the ductus arteriosus and oligohydramnios in the third trimester, use is contraindicated after 30 weeks gestation. In first and second trimesters, use only if potential benefit justifies potential fetal risk. |
■ FDA Black Box Warning
NSAIDs may increase the risk of serious cardiovascular events (e.g., myocardial infarction, stroke) and gastrointestinal events (e.g., bleeding, ulceration, perforation). However, due to low systemic absorption with ophthalmic use, this boxed warning is less clinically relevant but still applies.
| Common Effects | Burning sensation Stinging sensation |
| Serious Effects |
Hypersensitivity to ketorolac or any component of the formulation; patients with active ocular infection or advanced dry eye; history of asthma, urticaria, or allergic-type reactions to aspirin or other NSAIDs.
| Precautions | Use with caution in patients with compromised ocular surface, history of herpes simplex keratitis, bleeding tendencies, or those on anticoagulants. Prolonged use may delay wound healing. Monitor for signs of corneal epithelial breakdown or infection. |
| Food/Dietary |
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| Fetal Monitoring | Monitor maternal renal function, blood pressure, and signs of bleeding. Fetal monitoring includes ultrasound for oligohydramnios and ductus arteriosus constriction if used beyond 30 weeks gestation. |
| Fertility Effects | Ketorolac, like other NSAIDs, may impair female fertility by inhibiting prostaglandin synthesis, potentially affecting ovulation. Reversible upon discontinuation. No specific data on male fertility. |
| No known food interactions. No dietary restrictions required. |
| Clinical Pearls | ACULAR (ketorolac tromethamine ophthalmic solution) is an NSAID for ocular use. Preservative-free formulation is indicated for single-use to avoid corneal toxicity. Apply with caution in patients with bleeding disorders or those on anticoagulants due to risk of ocular bleeding. Prolonged use may delay corneal healing. Monitor for signs of keratitis or conjunctival hyperemia. |
| Patient Advice | Use exactly as prescribed; do not touch the dropper tip to any surface to avoid contamination. · Each single-use vial is for one dose only; discard after use to prevent infection. · Remove contact lenses before instillation and wait 10 minutes before reinserting. · Do not drive or operate machinery if vision is blurry after application. · Report eye pain, increased redness, or vision changes to your doctor immediately. |