Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ACULAR PRESERVATIVE FREE vs SUMATRIPTAN
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.
Selective 5-HT1B/1D receptor agonist; causes vasoconstriction of cranial arteries and inhibits trigeminal nerve transmission.
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.
Acute treatment of migraine with or without aura,Acute treatment of cluster headache episodes
1 drop into affected eye(s) four times daily (every 6 hours). Instill into conjunctival sac. Shake well before use.
Sumatriptan is available as oral tablets (25 mg, 50 mg, 100 mg), subcutaneous injection (6 mg/0.5 m L), and nasal spray (5 mg, 20 mg). For acute migraine: oral: 50-100 mg at onset, may repeat after 2 hours (max 200 mg/day). Subcutaneous: 6 mg at onset, may repeat after 1 hour (max 12 mg/24h). Nasal spray: 20 mg in one nostril at onset, may repeat after 2 hours (max 40 mg/day).
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).
2.5 hours (range 1–4 h); clinically relevant for redosing interval of ≥2 h.
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.
Primarily via monoamine oxidase A (MAO-A); minor via cytochrome P450 (CYP) enzymes.
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.
60% renal (as indole acetic acid metabolite), 40% fecal; <3% unchanged in urine.
99% bound to plasma proteins, primarily albumin.
14–21%, primarily to albumin and alpha-1-acid glycoprotein.
0.15-0.25 L/kg after oral administration; for ophthalmic use, systemic absorption is minimal, so Vd is not clinically meaningful.
2.0–3.3 L/kg; indicates extensive tissue 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: 15% (due to first-pass metabolism); subcutaneous: 97%; intranasal: 17% (with variability).
No dosage adjustment required for renal impairment. Drug is minimally absorbed systemically.
No specific dose adjustment is recommended for renal impairment. However, sumatriptan and its metabolites are excreted renally, and caution is advised in severe renal impairment (Cr Cl <15 m L/min). No specific GFR-based guidelines are established.
No dosage adjustment required for hepatic impairment. Drug is minimally absorbed systemically.
Contraindicated in severe hepatic impairment (Child-Pugh C). For mild to moderate hepatic impairment (Child-Pugh A or B): oral maximum dose is 50 mg; nasal spray: 5 mg single dose; subcutaneous: no specific adjustment, but caution advised due to reduced clearance.
Children ≥3 years: 1 drop into affected eye(s) four times daily. Safety and efficacy in children <3 years not established.
Not approved for pediatric use <18 years. However, off-label: adolescent (12-17 years): oral 25-100 mg at onset, may repeat after 2 hours (max 200 mg/day). Subcutaneous: 3-6 mg at onset (based on weight, e.g., 0.06 mg/kg). Nasal spray: 5-20 mg at onset.
No specific dosage adjustment required. Use same dose as adults; monitor for tolerability.
Limited data in elderly. Start with the lowest effective dose (e.g., oral 25 mg, subcutaneous 3 mg, nasal spray 5 mg). Caution due to potential for cardiovascular risk, hypertension, and reduced hepatic/renal function. Avoid in patients with uncontrolled hypertension or ischemic heart disease.
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.
Not recommended for use in patients with risk factors for coronary artery disease (e.g., hypertension, diabetes, smoking) unless a cardiovascular evaluation confirms absence of coronary artery disease.
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.
Risk of myocardial ischemia, infarction, and Prinzmetal's angina,Life-threatening serotonin syndrome with concomitant serotonergic drugs,Elevations in blood pressure,Increased risk of cerebrovascular events,Overuse headache with frequent use
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.
Ischemic heart disease,History of myocardial infarction,Uncontrolled hypertension,Hemiplegic or basilar migraine,Concomitant use of MAO-A inhibitors or within 2 weeks of discontinuation,Severe hepatic impairment,Hypersensitivity to sumatriptan
No known food interactions. No dietary restrictions required.
No significant food interactions. Avoid alcohol during migraine attacks as it can worsen headaches. May be taken with or without food.
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 Pregnancy Category C. In first trimester, no increased risk of major congenital malformations from available data; however, animal studies show embryo lethality and increased malformations at high doses. Second and third trimester risks include potential for uterine hypertonus and fetal hypoxia during maternal use for migraine attacks; avoid during third trimester due to risk of premature uterine contractions.
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.
Sumatriptan is excreted into human breast milk with a relative infant dose of 3.5% of maternal weight-adjusted dose (M/P ratio approximately 0.6-4.3). Clinical studies show no adverse effects in breastfed infants; however, wait at least 12 hours after injection or 24 hours after oral dose to breastfeed to minimize exposure.
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 dose adjustments required for pregnancy based on pharmacokinetic changes; however, lower starting doses may be considered due to increased sensitivity to vascular effects. Avoid use in preeclampsia or uncontrolled hypertension.
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.
Sumatriptan is a 5-HT1B/1D receptor agonist used for acute migraine. It is available in oral, nasal, subcutaneous, and rectal formulations. Onset of action is fastest with subcutaneous injection (10-15 minutes). Avoid use within 24 hours of other triptans or ergot alkaloids. Contraindicated in patients with ischemic heart disease, cerebrovascular disease, uncontrolled hypertension, or hemiplegic/basilar migraine. Monitor for serotonin syndrome when combined with SSRIs/SNRIs.
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 sumatriptan at the first sign of migraine headache for best results.,Do not exceed the recommended dose: maximum 100 mg orally or 20 mg intranasally per single dose, with a maximum of 200 mg daily for oral formulations.,Seek emergency medical attention if you experience chest pain, shortness of breath, irregular heartbeat, or signs of stroke.,Avoid driving or operating machinery until you know how sumatriptan affects you, as it may cause dizziness or drowsiness.,Inform your doctor if you have heart disease, high blood pressure, or are pregnant or breastfeeding.
No interactions on record
"Concurrent use of sumatriptan, a serotonin 5-HT1B/1D receptor agonist, and rasagiline, a selective monoamine oxidase B (MAO-B) inhibitor, can lead to serotonin syndrome due to excessive serotonergic activity in the central nervous system. Rasagiline inhibits the metabolism of serotonin, while sumatriptan indirectly increases serotonin release; their combination may result in life-threatening neuromuscular excitation, autonomic instability, and altered mental status. Symptoms may include hyperthermia, rigidity, myoclonus, and rapid fluctuations in vital signs, requiring immediate medical intervention."
"Sumatriptan, a 5-HT1B/1D receptor agonist used for migraine, and sulpiride, a dopamine D2 receptor antagonist with atypical antipsychotic properties, may exhibit additive or synergistic effects on the central nervous system. This combination can potentially increase the risk of serotonin syndrome (due to sumatriptan's serotonergic activity) and may also lead to enhanced extrapyramidal symptoms or neuroleptic malignant syndrome via combined dopaminergic antagonism. Clinical outcomes may include hyperthermia, rigidity, altered mental status, and autonomic instability."
"The combination of sumatriptan (a 5-HT1B/1D receptor agonist) and paroxetine (a selective serotonin reuptake inhibitor) increases the risk of serotonin syndrome, a potentially life-threatening condition characterized by neuromuscular excitation, autonomic instability, and altered mental status. This interaction is due to additive serotonergic effects, as both drugs enhance serotonin activity in the central nervous system. Clinical outcomes range from mild symptoms (tremor, hyperreflexia, diaphoresis) to severe manifestations (hyperthermia, rigidity, seizures) and require immediate medical attention."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ACULAR PRESERVATIVE FREE vs SUMATRIPTAN, 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.. SUMATRIPTAN is a 5-HT1 Agonist that works by Selective 5-HT1B/1D receptor agonist; causes vasoconstriction of cranial arteries and inhibits trigeminal nerve transmission.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ACULAR PRESERVATIVE FREE and SUMATRIPTAN 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 SUMATRIPTAN is: Sumatriptan is available as oral tablets (25 mg, 50 mg, 100 mg), subcutaneous injection (6 mg/0.5 m L), and nasal spray (5 mg, 20 mg). For acute migraine: oral: 50-100 mg at onset, may repeat after 2 hours (max 200 mg/day). Subcutaneous: 6 mg at onset, may repeat after 1 hour (max 12 mg/24h). Nasal spray: 20 mg in one nostril at onset, may repeat after 2 hours (max 40 mg/day).. 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 SUMATRIPTAN 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. SUMATRIPTAN is classified as Category D/X. FDA Pregnancy Category C. In first trimester, no increased risk of major congenital malformations from available data; however, animal studies show embryo lethality and increased m. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.