Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
FROVA vs CALAN
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Selective serotonin 5-HT1B/1D receptor agonist; causes vasoconstriction of cranial arteries and inhibits trigeminal nerve transmission.
Verapamil inhibits calcium ion influx through voltage-gated L-type calcium channels in cardiac and vascular smooth muscle, leading to decreased myocardial contractility, slowed AV conduction, and vasodilation.
Acute treatment of migraine with or without aura in adults
Angina pectoris (chronic stable, vasospastic, unstable),Essential hypertension,Supraventricular tachyarrhythmias (e.g., atrial fibrillation, atrial flutter, PSVT)
2.5 mg orally once daily; maximum 5 mg/day.
Initial: 80-120 mg orally 3 times daily; maintenance: 240-480 mg/day in 3-4 divided doses. IV: 5-10 mg over 2 minutes, may repeat after 15-30 minutes.
Terminal elimination half-life is 26 hours. This prolonged half-life supports once-daily dosing and provides sustained headache relief.
Terminal elimination half-life is 3-7 hours for immediate-release; can be prolonged to 12-16 hours with sustained-release due to slow absorption; increased in hepatic impairment.
Hepatic via CYP1A2; primary metabolite is 5-hydroxyfrovatriptan.
Extensively metabolized in the liver via CYP3A4, CYP1A2, and CYP2C8 isoenzymes; undergoes N-dealkylation and O-demethylation; first-pass metabolism results in low bioavailability (20-35%).
Primarily hepatic metabolism followed by renal and fecal elimination. Approximately 62% of the dose is recovered in urine (mainly as metabolites, <10% unchanged) and 32% in feces.
Approximately 70% renal (3-4% unchanged, remainder as metabolites) and 25% biliary/fecal.
Approximately 15% bound to plasma proteins (primarily albumin).
Approximately 90% bound to plasma proteins, primarily albumin.
Volume of distribution (Vd) is approximately 2.4 L/kg, indicating extensive tissue distribution.
Vd 4-5 L/kg; indicates extensive tissue distribution beyond plasma volume.
Oral bioavailability is approximately 30% due to first-pass metabolism.
Oral bioavailability is 20-35% due to extensive first-pass hepatic metabolism; IV bioavailability is 100%.
No adjustment required for GFR ≥30 m L/min; use not recommended for GFR <30 m L/min.
Cr Cl <30 m L/min: reduce dose by 50% and monitor carefully.
Contraindicated in severe hepatic impairment (Child-Pugh C); use with caution in moderate impairment (Child-Pugh B) at reduced dose (2.5 mg every other day).
Child-Pugh A: 50% of normal dose; Child-Pugh B: 25% of normal dose; Child-Pugh C: contraindicated or use with extreme caution.
Not approved for use in pediatric patients; safety and efficacy not established.
Oral: 4-8 mg/kg/day in 3 divided doses; IV: 0.1-0.3 mg/kg over 2 minutes, max 5 mg.
No specific dose adjustment, but monitor for increased sensitivity and renal function due to age-related decline.
Start at lowest dose (e.g., 40 mg 3 times daily) and titrate slowly; monitor for hypotension and bradycardia.
Do not use in patients with ischemic heart disease, coronary artery vasospasm, or other significant cardiovascular conditions.
Contains verapamil hydrochloride. Risk of serious adverse effects including hypotension, bradycardia, AV block, and cardiac arrest. Must not be administered to patients with severe left ventricular dysfunction, cardiogenic shock, or sick sinus syndrome (unless paced).
Risk of myocardial ischemia, cerebral hemorrhage, cardiac arrhythmias; serotonin syndrome with concomitant serotonergic drugs; medication overuse headache; severe hepatic impairment.
May cause hypotension, bradycardia, AV block, and exacerbation of heart failure. Avoid in patients with pre-existing conduction abnormalities. Use caution with beta-blockers, digoxin, and CYP3A4 inhibitors. Abrupt withdrawal may exacerbate angina. May increase lithium and carbamazepine levels.
Ischemic heart disease, coronary artery vasospasm, history of stroke/TIA, peripheral vascular disease, uncontrolled hypertension, hemiplegic or basilar migraine, recent MAOI use, hypersensitivity.
Severe left ventricular dysfunction, cardiogenic shock, sick sinus syndrome (without pacemaker), second- or third-degree AV block (without pacemaker), atrial flutter/fibrillation with accessory bypass tract (e.g., WPW syndrome), concurrent use of IV beta-blockers.
No significant food interactions. Grapefruit juice does not affect frovatriptan metabolism. Avoid alcohol during migraine attacks as it may worsen headache or increase drowsiness.
Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 metabolism, increasing verapamil levels and risk of toxicity. Limit alcohol intake as it may enhance hypotensive effects. High-fat meals may delay absorption but not extent; take consistently with regard to meals.
Frovatriptan is contraindicated in pregnancy due to potential fetal harm. In animal studies, frovatriptan was associated with reduced fetal weights and increased incidence of fetal abnormalities at maternal toxic doses. In humans, there is no adequate data; however, triptans as a class may increase risk of preterm delivery, low birth weight, and possibly orofacial clefts when used in the first trimester. Use during first trimester: Risk category not formally assigned but should be avoided. Second and third trimesters: Avoid due to potential for uterine contractions and reduced placental perfusion. Labor and delivery: Contraindicated as it may cause uterine hypertonicity and fetal distress.
First trimester: No increased risk of major malformations observed in human studies; animal studies show fetal toxicity at high doses. Second and third trimesters: May cause fetal bradycardia, hypotension, and impaired placental perfusion; avoid use for pregnancy-induced hypertension due to risk of fetal hypoxia.
Frovatriptan is excreted into breast milk in low amounts; the M/P ratio is approximately 2.6:1 (milk to plasma ratio). The relative infant dose is estimated at 1.5-3.5% of the maternal weight-adjusted dose. While adverse effects in breastfed infants have not been reported, caution is advised due to potential for vasoconstriction and gastrointestinal disturbances. Consider pumping and discarding milk for 24 hours after dose.
Verapamil (CALAN) is excreted into breast milk; M/P ratio approximately 0.6. The relative infant dose is low (estimated <5% of maternal weight-adjusted dose). No adverse effects reported in breastfed infants. Caution in preterm infants or those with renal impairment.
Pharmacokinetic changes in pregnancy (e.g., increased plasma volume, hepatic metabolism alterations) may reduce frovatriptan exposure. However, due to contraindication and lack of safety data, no adjusted dosing is recommended. Use in pregnancy is not advised; alternative medications with better safety profiles (e.g., sumatriptan) should be considered if triptan therapy is necessary.
Pregnancy may increase clearance of verapamil; monitoring of therapeutic effect advised. Dose may need adjustment based on clinical response. Avoid use in pregnancy-induced hypertension.
Frovatriptan has the longest half-life (~26 hours) among triptans, which may be beneficial for patients with prolonged migraine attacks or frequent recurrence. Onset of action is slower (~2-4 hours) compared to sumatriptan. Use with caution in patients with cardiovascular risk factors due to vasoconstrictive effects. Contraindicated within 24 hours of other triptans or ergotamine-containing medications.
Calan (verapamil) is a class IV antiarrhythmic and calcium channel blocker. Use caution in patients with hepatic impairment due to reduced clearance; dose adjustment may be needed. Avoid in patients with pre-existing bradycardia, second- or third-degree AV block, or sick sinus syndrome unless a pacemaker is present. May increase digoxin levels; monitor digoxin concentrations. Use with caution in patients with hypertrophic cardiomyopathy. For IV administration, have calcium gluconate available to reverse hypotension or bradycardia. Not recommended for use in acute myocardial infarction or cardiogenic shock.
Take FROVA at the first sign of a migraine headache, but it can be taken any time during an attack.,Do not exceed one tablet (2.5 mg) in a 24-hour period; if headache returns, repeat dose after at least 2 hours.,Do not take within 24 hours of another triptan or ergotamine-type medication.,Common side effects include dizziness, fatigue, tingling, and flushing. Report chest tightness, palpitations, or shortness of breath immediately.,Seek emergency care if headache worsens or is accompanied by stiff neck, fever, or vision changes.,Inform your doctor if you have heart disease, high blood pressure, liver disease, or are pregnant or breastfeeding.
Take exactly as prescribed; do not skip doses or stop abruptly without consulting your doctor.,Avoid grapefruit juice as it can increase verapamil levels and risk of side effects.,If you miss a dose, take it as soon as you remember unless it is almost time for the next dose; do not double the dose.,Avoid alcohol as it may worsen side effects like dizziness or low blood pressure.,Report symptoms of bradycardia (slow heart rate), palpitations, shortness of breath, or swelling of ankles/feet.,This medication may cause dizziness; avoid driving or operating machinery until you know how it affects you.,Do not consume grapefruit or its juice during treatment.,Keep a regular medication schedule and do not change brands without doctor approval.
"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 FROVA vs CALAN, answered by our medical review team.
FROVA is a Antimigraine (triptan) that works by Selective serotonin 5-HT1B/1D receptor agonist; causes vasoconstriction of cranial arteries and inhibits trigeminal nerve transmission.. CALAN is a Calcium Channel Blocker that works by Verapamil inhibits calcium ion influx through voltage-gated L-type calcium channels in cardiac and vascular smooth muscle, leading to decreased myocardial contractility, slowed AV conduction, and vasodilation.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between FROVA and CALAN 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 FROVA is: 2.5 mg orally once daily; maximum 5 mg/day.. The standard adult dose of CALAN is: Initial: 80-120 mg orally 3 times daily; maintenance: 240-480 mg/day in 3-4 divided doses. IV: 5-10 mg over 2 minutes, may repeat after 15-30 minutes.. 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 FROVA and CALAN 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. FROVA is classified as Category C. Frovatriptan is contraindicated in pregnancy due to potential fetal harm. In animal studies, frovatriptan was associated with reduced fetal weights and increased incidence of fetal. CALAN is classified as Category C. First trimester: No increased risk of major malformations observed in human studies; animal studies show fetal toxicity at high doses. Second and third trimesters: May cause fetal . Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.