Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ACULAR PRESERVATIVE FREE vs ACTAHIST
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
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.
Antihistamine; binds to histamine H1 receptors, blocking the effects of histamine; also exhibits anticholinergic and mild sedative properties.
FDA-approved: Treatment of ocular inflammation and pain following cataract surgery and corneal refractive surgery.,Off-label: Relief of seasonal allergic conjunctivitis symptoms, management of cystoid macular edema, and treatment of postoperative inflammation in other ocular procedures.
Symptomatic relief of allergic rhinitis,Urticaria,Off-label: motion sickness,Off-label: insomnia
1 drop into affected eye(s) four times daily (every 6 hours). Instill into conjunctival sac. Shake well before use.
1.34 mg (one capsule) orally twice daily.
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).
6.9 ± 1.7 hours in adults; prolonged to 12-18 hours in elderly or patients with hepatic impairment, requiring dosing interval adjustment.
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.
Hepatic metabolism via CYP450 enzymes (primarily CYP3A4 and CYP2D6); major metabolite is inactive.
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.
Primarily renal (approximately 85% as unchanged drug and metabolites) and fecal (15%) via biliary elimination.
99% bound to plasma proteins, primarily albumin.
92% bound to albumin.
0.15-0.25 L/kg after oral administration; for ophthalmic use, systemic absorption is minimal, so Vd is not clinically meaningful.
0.9 ± 0.3 L/kg, indicating extensive extravascular distribution.
Ophthalmic administration: Systemic bioavailability is approximately 0.5-1% after ocular instillation due to low corneal penetration and rapid clearance; oral bioavailability is 100%.
Oral: 68% ± 12% due to first-pass metabolism.
No dosage adjustment required for renal impairment. Drug is minimally absorbed systemically.
No dose adjustment required for mild to moderate renal impairment. Safety not established for severe impairment (GFR <30 m L/min).
No dosage adjustment required for hepatic impairment. Drug is minimally absorbed systemically.
No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not recommended for severe hepatic impairment (Child-Pugh C).
Children ≥3 years: 1 drop into affected eye(s) four times daily. Safety and efficacy in children <3 years not established.
Not indicated for pediatric patients under 12 years of age. Safety and efficacy not established.
No specific dosage adjustment required. Use same dose as adults; monitor for tolerability.
No specific dose adjustment recommended; monitor for increased anticholinergic effects and cognitive impairment.
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.
None.
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.
May cause drowsiness; caution when driving or operating machinery. Avoid alcohol. Use with caution in patients with narrow-angle glaucoma, prostatic hyperplasia, or urinary retention. Geriatric patients more sensitive to anticholinergic effects. Pediatric patients <6 years: not recommended.
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.
Hypersensitivity to any component. Newborns or premature infants. Breastfeeding (contraindicated due to risk of adverse effects in infants). Concomitant use with MAOIs.
No known food interactions. No dietary restrictions required.
Avoid high-tyramine foods (aged cheese, cured meats, fermented products) if taking MAOIs. Grapefruit juice may increase phenylephrine absorption; limit intake.
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.
ACTAHIST (brompheniramine/phenylephrine) pregnancy category C. Inadequate human data; animal studies show no malformations at therapeutic doses. First trimester: theoretical risk from vasoconstrictive effects (phenylephrine) possibly reducing uterine blood flow; avoid if possible. Second/third trimester: phenylephrine may cause fetal hypoxia via placental vasoconstriction; use only if benefit outweighs risk. No known structural teratogenicity.
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.
Brompheniramine is excreted in breast milk in small amounts; M/P ratio not established. Phenylephrine has minimal excretion. Due to anticholinergic effects, may reduce milk production or cause sedation in infants. Use caution; prefer non-sedating alternatives if possible.
No specific pharmacokinetic studies in pregnancy. Dosing should be at the lowest effective dose for the shortest duration. Avoid use after 30 weeks gestation. No adjustment for first or second trimester unless renal function changes.
No specific pharmacokinetic studies. Increased plasma volume and renal clearance in pregnancy may reduce drug levels, but efficacy threshold remains. No dose adjustment recommended; use the lowest effective dose for shortest duration due to potential risks.
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.
Actahist is a combination antihistamine-decongestant (chlorpheniramine/phenylephrine). Avoid in patients with hypertension, severe coronary artery disease, or MAOI use. Monitor for sedation and urinary retention, especially in elderly males with BPH.
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.
Take with food or milk to reduce stomach upset.,Avoid alcohol and CNS depressants as they can increase drowsiness.,Do not drive or operate machinery until you know how this medication affects you.,Contact your doctor if you experience chest pain, rapid heartbeat, or difficulty urinating.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ACULAR PRESERVATIVE FREE vs ACTAHIST, answered by our medical review team.
ACULAR PRESERVATIVE FREE is a NSAID Ophthalmic that works by 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.. ACTAHIST is a Antihistamine that works by Antihistamine; binds to histamine H1 receptors, blocking the effects of histamine; also exhibits anticholinergic and mild sedative properties.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ACULAR PRESERVATIVE FREE and ACTAHIST depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of ACULAR PRESERVATIVE FREE is: 1 drop into affected eye(s) four times daily (every 6 hours). Instill into conjunctival sac. Shake well before use.. The standard adult dose of ACTAHIST is: 1.34 mg (one capsule) orally twice daily.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between ACULAR PRESERVATIVE FREE and ACTAHIST in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. ACULAR PRESERVATIVE FREE is classified as Category C. 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. ACTAHIST is classified as Category C. ACTAHIST (brompheniramine/phenylephrine) pregnancy category C. Inadequate human data; animal studies show no malformations at therapeutic doses. First trimester: theoretical risk f. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.