Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
FROVATRIPTAN SUCCINATE vs ACULAR
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.
Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis, which decreases inflammation, pain, and fever.
Acute treatment of migraine with or without aura in adults
Treatment of postoperative inflammation in patients who have undergone cataract extraction,Relief of ocular itching due to seasonal allergic conjunctivitis
2.5 mg orally once, may repeat after 2 hours if needed; maximum 7.5 mg in 24 hours.
One drop of 0.5% ophthalmic solution into the affected eye(s) four times daily.
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 half-life: 1.8 hours (ketorolac tromethamine); clinical context: short half-life supports dosing every 6 hours for acute pain, but prolonged in elderly or renal impairment (↑ to 5-6 hours, thus dose reduction required).
Primarily hepatic via CYP1A2; undergoes oxidative metabolism; some contribution from CYP2D6.
Hepatic metabolism primarily via cytochrome P450 2C9 (CYP2C9).
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.
Renal: ~80% as unchanged drug and glucuronide conjugates; biliary/fecal: ~20%
Approximately 30% bound to plasma proteins, primarily albumin. Low protein binding suggests minimal displacement interactions.
99% bound; primary binding protein: albumin.
Mean volume of distribution is approximately 2.7 L/kg, indicating extensive extravascular distribution, consistent with its CNS penetration for migraine relief.
0.11-0.25 L/kg; clinical meaning: low Vd indicates primarily confined to extracellular compartment (plasma and interstitial fluid), minimal tissue penetration.
Oral bioavailability is approximately 30% due to first-pass metabolism. No other routes are clinically approved; the drug is only available orally.
Ophthalmic: ~2% systemic absorption after topical instillation (due to corneal permeability and nasolacrimal drainage); oral formulation not used for Acular (ophthalmic only).
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.
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.
Safety and efficacy not established in pediatric patients under 18 years of age.
Safety and efficacy in pediatric patients have not been established; use not recommended.
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 dosing as for younger adults.
Not recommended for use in patients with risk factors for coronary artery disease (CAD) unless a cardiovascular evaluation confirms absence of CAD.
No FDA boxed warning.
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.
May increase bleeding time due to inhibition of platelet aggregation; use with caution in patients with known bleeding tendencies or those receiving other medications that may prolong bleeding time.,May cause corneal effects including keratitis and corneal thinning; discontinue if corneal epithelial breakdown occurs.,Use with caution in patients with prior sensitivity to aspirin, phenylacetic acid derivatives, or other NSAIDs.,May delay wound healing or exacerbate infections; avoid use in patients with active epithelial herpes simplex keratitis.
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 tromethamine or any component of the formulation,History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs,Active epithelial herpes simplex keratitis,Late pregnancy (third trimester) due to risk of premature closure of ductus arteriosus
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. Avoid alcohol if concomitant oral NSAIDs are used due to increased risk of gastrointestinal bleeding, but this is not specific to ophthalmic use.
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.
Pregnancy Category C. No adequate studies in pregnant women. Ketorolac tromethamine, like other NSAIDs, may cause premature closure of the ductus arteriosus and fetal renal impairment in the third trimester. First and second trimester use should be avoided unless clearly needed. The potential benefits should be weighed against the risks.
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 at low levels. The M/P ratio is not well defined. Due to potential adverse effects in nursing infants, caution is advised. Use only if clearly indicated and consider alternative agents.
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 dose adjustments are recommended for pregnancy; however, use the lowest effective dose for the shortest duration due to potential fetal risks. Physiological changes in pregnancy (increased volume of distribution, renal clearance) may alter pharmacokinetics, but no formal studies justify dose modification.
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 a nonsteroidal anti-inflammatory drug (NSAID) used for ocular inflammation. Avoid concomitant use with other NSAIDs or corticosteroids due to increased risk of corneal adverse events. Use with caution in patients with bleeding disorders or those on anticoagulants, as it may increase bleeding tendency. Monitor for corneal toxicity, especially in patients with compromised corneal integrity. Ensure proper storage at room temperature and discard if solution changes color or becomes cloudy.
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.
Do not touch the dropper tip to any surface to avoid contamination.,Remove contact lenses before instillation and wait at least 15 minutes before reinserting.,Apply pressure to the inner corner of the eye (nasolacrimal occlusion) for 1 minute after instillation to reduce systemic absorption.,Do not use while wearing soft contact lenses, as the preservative may be absorbed.,Report any signs of corneal problems such as pain, redness, or vision changes immediately.,Use exactly as prescribed and do not share the medication with others.
"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, 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 is a NSAID Ophthalmic that works by Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis, which decreases inflammation, pain, and fever.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between FROVATRIPTAN SUCCINATE and ACULAR 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 is: One drop of 0.5% ophthalmic solution into the affected eye(s) four times 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 FROVATRIPTAN SUCCINATE and ACULAR 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 is classified as Category C. Pregnancy Category C. No adequate studies in pregnant women. Ketorolac tromethamine, like other NSAIDs, may cause premature closure of the ductus arteriosus and fetal renal impairm. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.