Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
FROVATRIPTAN SUCCINATE vs ACULAR PRESERVATIVE FREE
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Selective 5-HT1B/1D receptor agonist; causes vasoconstriction of intracranial extracerebral blood vessels and inhibits nociceptive trigeminal nerve transmission.
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.
Acute treatment of migraine with or without aura in adults
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.
2.5 mg orally once, may repeat after 2 hours if needed; maximum 7.5 mg in 24 hours.
1 drop into affected eye(s) four times daily (every 6 hours). Instill into conjunctival sac. Shake well before use.
Terminal elimination half-life is approximately 4-5 hours (range 3-6 hours). This relatively short half-life supports its use for acute migraine treatment, though it may allow for repeat dosing within 24 hours if necessary.
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).
Primarily hepatic via CYP1A2; undergoes oxidative metabolism; some contribution from CYP2D6.
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 hepatic metabolism via CYP1A2; renal excretion accounts for ~10% of unchanged drug. Total recovery in urine and feces is ~90% over 72 hours, with ~30% in urine (mostly metabolites) and ~60% in feces.
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.
Approximately 30% bound to plasma proteins, primarily albumin. Low protein binding suggests minimal displacement interactions.
99% bound to plasma proteins, primarily albumin.
Mean volume of distribution is approximately 2.7 L/kg, indicating extensive extravascular distribution, consistent with its CNS penetration for migraine relief.
0.15-0.25 L/kg after oral administration; for ophthalmic use, systemic absorption is minimal, so Vd is not clinically meaningful.
Oral bioavailability is approximately 30% due to first-pass metabolism. No other routes are clinically approved; the drug is only available orally.
Ophthalmic administration: Systemic bioavailability is approximately 0.5-1% after ocular instillation due to low corneal penetration and rapid clearance; oral bioavailability is 100%.
Contraindicated in severe renal impairment (Cr Cl <15 m L/min). For moderate impairment (Cr Cl 15-29 m L/min), maximum dose 2.5 mg per 24 hours. No adjustment for mild impairment.
No dosage adjustment required for renal impairment. Drug is minimally absorbed systemically.
Contraindicated in moderate to severe hepatic impairment (Child-Pugh class B or C). For mild impairment (Child-Pugh class A), no dose adjustment required.
No dosage adjustment required for hepatic impairment. Drug is minimally absorbed systemically.
Safety and efficacy not established in pediatric patients under 18 years of age.
Children ≥3 years: 1 drop into affected eye(s) four times daily. Safety and efficacy in children <3 years not established.
No specific dose adjustment recommended based on age alone, but use with caution due to increased risk of adverse effects (e.g., cardiovascular events) and potential age-related renal impairment.
No specific dosage adjustment required. Use same dose as adults; monitor for tolerability.
Not recommended for use in patients with risk factors for coronary artery disease (CAD) unless a cardiovascular evaluation confirms absence of CAD.
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.
Serious cardiac events including myocardial ischemia, infarction, and arrhythmias; cerebrovascular events including stroke; serotonin syndrome when coadministered with serotonergic drugs; increases in blood pressure; peripheral vascular ischemia; medication overuse headache; severe hepatic impairment.
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.
Ischemic heart disease; history of myocardial infarction; coronary artery vasospasm; uncontrolled hypertension; hemiplegic or basilar migraine; concomitant use with ergotamines or 5-HT1 agonists; severe hepatic impairment; hypersensitivity to frovatriptan.
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.
No specific food interactions. Avoid alcohol as it can exacerbate migraine and increase sedation risk. Grapefruit juice may increase frovatriptan levels due to CYP1A2 inhibition; limit or avoid consumption.
No known food interactions. No dietary restrictions required.
Pregnancy Category C. No adequate well-controlled studies in pregnant women. In animal studies, frovatriptan caused fetal toxicity (decreased fetal weight, increased skeletal variations) at doses ≥50 mg/kg/day (approximately 100 times the MRHD). Increased risk of maternal toxicity (reduced weight gain) at high doses. Potential risk of uterine contractions and reduced uterine blood flow due to vasoconstrictive properties. Use only if potential benefit justifies risk to fetus.
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.
Excreted in rat milk; no human data. M/P ratio unknown. Caution recommended due to potential adverse effects in nursing infants (e.g., vasoconstriction, serotonin syndrome). Decision to breastfeed or discontinue drug should consider importance of drug to mother.
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.
No specific pharmacokinetic studies in pregnancy. Dose adjustment not established; use lowest effective dose. Caution in third trimester due to possible uterine vasoconstriction. Consider alternative therapy if frequent use needed.
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.
Frovatriptan has a long half-life (~26 h), making it useful for prolonged migraine attacks or for menstrual migraine prophylaxis when dosed perimenstrually. Onset is slower than other triptans; not ideal for acute severe migraine requiring rapid relief. Contraindicated with MAOIs, potent CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin), and within 24 h of another triptan or ergotamine. Avoid in patients with hemiplegic or basilar migraine, ischemic heart disease, 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.
Take frovatriptan at the first sign of a migraine headache, not during the aura or for prevention of typical migraines.,Swallow tablets whole with water; do not crush or chew.,If the headache returns after initial relief, a second dose may be taken after at least 2 hours, with a maximum of 3 tablets per 24 hours.,Do not use frovatriptan if you have taken another triptan or ergotamine within the last 24 hours.,Seek emergency medical attention if you experience chest pain, shortness of breath, irregular heartbeat, or signs of serotonin syndrome (e.g., agitation, hallucinations, rapid heart rate, fever, muscle stiffness).,Avoid alcohol during use as it may worsen headache or increase side effects.,Inform your doctor if you are pregnant, breastfeeding, or have liver or kidney disease.,Do not drive or operate machinery until you know how frovatriptan affects you, as it may cause dizziness or drowsiness.
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.
"Frovatriptan, a serotonin 5-HT1B/1D receptor agonist used for acute migraine, and chlorpromazine, a first-generation antipsychotic with potent dopamine D2 receptor antagonism, can lead to additive serotonin excess when co-administered due to their combined serotonergic activity. Chlorpromazine also possesses weak serotonin reuptake inhibition properties, increasing the risk of serotonin syndrome, a potentially life-threatening condition characterized by neuromuscular excitation, autonomic instability, and altered mental status. Additionally, chlorpromazine may antagonize the vasoconstrictive effects of triptans via alpha-adrenergic blockade, potentially reducing migraine relief efficacy."
"Frovatriptan, a triptan used for migraine, is primarily metabolized by CYP1A2. Clotrimazole, an azole antifungal, inhibits CYP1A2, thereby reducing the clearance of frovatriptan. This can lead to increased systemic exposure to frovatriptan, potentially elevating the risk of triptan-related adverse effects such as serotonin syndrome, coronary vasospasm, and hypertension."
"Coadministration of frovatriptan, a serotonin receptor agonist metabolized primarily by CYP1A2, with simeprevir, a potent CYP3A4 inhibitor and weak CYP1A2 inducer, may result in reduced clearance of simeprevir due to competitive inhibition of CYP3A4 by frovatriptan or its metabolites. This interaction can lead to increased simeprevir plasma concentrations, elevating the risk of hepatotoxicity, photosensitivity reactions, and QT prolongation. Conversely, frovatriptan exposure is not significantly altered as its metabolism via CYP1A2 is minimally affected by simeprevir."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about FROVATRIPTAN SUCCINATE vs ACULAR PRESERVATIVE FREE, answered by our medical review team.
FROVATRIPTAN SUCCINATE is a 5-HT1 Agonist that works by Selective 5-HT1B/1D receptor agonist; causes vasoconstriction of intracranial extracerebral blood vessels and inhibits nociceptive trigeminal nerve transmission.. 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.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between FROVATRIPTAN SUCCINATE and ACULAR PRESERVATIVE FREE 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 FROVATRIPTAN SUCCINATE is: 2.5 mg orally once, may repeat after 2 hours if needed; maximum 7.5 mg in 24 hours.. 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.. 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 FROVATRIPTAN SUCCINATE and ACULAR PRESERVATIVE FREE 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. FROVATRIPTAN SUCCINATE is classified as Category D/X. Pregnancy Category C. No adequate well-controlled studies in pregnant women. In animal studies, frovatriptan caused fetal toxicity (decreased fetal weight, increased skeletal varia. 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. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.