Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
FROVA vs CADUET
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.
Amlodipine: Dihydropyridine calcium channel blocker that inhibits calcium ion influx across cardiac and vascular smooth muscle cell membranes, causing vasodilation and reduced peripheral vascular resistance. Atorvastatin: HMG-Co A reductase inhibitor that competitively inhibits the conversion of HMG-Co A to mevalonate, reducing cholesterol synthesis in the liver.
Acute treatment of migraine with or without aura in adults
Hypertension,Coronary artery disease,Hyperlipidemia (as adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels, and to increase HDL-C),Prevention of cardiovascular events in patients with multiple risk factors
2.5 mg orally once daily; maximum 5 mg/day.
CADUET (amlodipine/atorvastatin) is available as tablets of 2.5/10, 2.5/20, 2.5/40, 5/10, 5/20, 5/40, 5/80, 10/10, 10/20, 10/40, and 10/80 mg amlodipine/atorvastatin. Initial dose depends on current antihypertensive and lipid-lowering therapy. Usual starting dose is 5/10 mg orally once daily; titrate at intervals of 2-4 weeks based on blood pressure and LDL-C goals. Maximum daily dose: amlodipine 10 mg; atorvastatin 80 mg.
Terminal elimination half-life is 26 hours. This prolonged half-life supports once-daily dosing and provides sustained headache relief.
Amlodipine: terminal half-life 30-50 h (enables once-daily dosing). Atorvastatin: terminal half-life ~14 h, but active metabolites (ortho- and para-hydroxy atorvastatin) have half-life 20-30 h; clinically, pharmacodynamic half-life (HMG-Co A reductase inhibition) is ~20-30 h.
Hepatic via CYP1A2; primary metabolite is 5-hydroxyfrovatriptan.
Amlodipine: Extensively metabolized in the liver via CYP3A4 to inactive metabolites. Atorvastatin: Metabolized in the liver primarily by CYP3A4 to active ortho- and para-hydroxylated metabolites.
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.
Amlodipine: 60% renal (metabolites), 20-25% biliary/fecal. Atorvastatin: 1% renal (unchanged), 90% biliary/fecal (≥70% as metabolites).
Approximately 15% bound to plasma proteins (primarily albumin).
Amlodipine: ~93% bound to plasma proteins. Atorvastatin: ≥98% bound to plasma proteins (mainly albumin).
Volume of distribution (Vd) is approximately 2.4 L/kg, indicating extensive tissue distribution.
Amlodipine: Vd ~21 L/kg (large, indicating extensive tissue distribution). Atorvastatin: Vd ~6.2 L/kg (moderately large, suggesting distribution into tissues).
Oral bioavailability is approximately 30% due to first-pass metabolism.
Oral: amlodipine 64-90%; atorvastatin ~14% (low due to first-pass metabolism); food reduces rate but not extent of absorption.
No adjustment required for GFR ≥30 m L/min; use not recommended for GFR <30 m L/min.
No dosage adjustment required for mild to moderate renal impairment (Cr Cl ≥30 m L/min). For severe renal impairment (Cr Cl <30 m L/min), use atorvastatin with caution; maximum atorvastatin dose is 20 mg daily. Amlodipine is not dialyzable.
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).
Contraindicated in active liver disease or unexplained persistent elevations of serum transaminases. For Child-Pugh Class A or B hepatic impairment: atorvastatin dose should be reduced; maximum atorvastatin dose is 20 mg daily. Amlodipine clearance is decreased; initial amlodipine dose should be 2.5 mg daily. No data for Child-Pugh Class C; use contraindicated.
Not approved for use in pediatric patients; safety and efficacy not established.
Not recommended for pediatric patients. Safety and efficacy in children <10 years have not been established. For patients 10-17 years with heterozygous familial hypercholesterolemia, atorvastatin monotherapy is used; CADUET is not indicated.
No specific dose adjustment, but monitor for increased sensitivity and renal function due to age-related decline.
Elderly patients (≥65 years) may have increased sensitivity to amlodipine; start at the lower end of dosing range (2.5 mg amlodipine component). Atorvastatin dose adjustment not required based on age alone. Monitor for hypotension and other adverse effects.
Do not use in patients with ischemic heart disease, coronary artery vasospasm, or other significant cardiovascular conditions.
HMG-Co A reductase inhibitors (statins) can cause fetal harm; use in pregnant women is contraindicated. Caduet contains atorvastatin; therefore, it is contraindicated in pregnant women.
Risk of myocardial ischemia, cerebral hemorrhage, cardiac arrhythmias; serotonin syndrome with concomitant serotonergic drugs; medication overuse headache; severe hepatic impairment.
Myopathy/Rhabdomyolysis: Risk increased with higher doses, age >65, renal impairment, hypothyroidism, and concurrent use of CYP3A4 inhibitors or other drugs that cause myopathy.,Hepatic effects: Elevated liver enzymes; perform liver function tests before initiation and as clinically indicated.,Fetal toxicity: May cause fetal harm; advise females of reproductive age to use effective contraception.,Peripheral edema: More common with higher doses of amlodipine, especially in females.,Hypotension: In patients with severe aortic stenosis.
Ischemic heart disease, coronary artery vasospasm, history of stroke/TIA, peripheral vascular disease, uncontrolled hypertension, hemiplegic or basilar migraine, recent MAOI use, hypersensitivity.
Active liver disease or unexplained persistent elevations of hepatic transaminases,Pregnancy,Breastfeeding (due to potential for serious adverse reactions in nursing infants),Hypersensitivity to amlodipine, atorvastatin, or any component of the formulation
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 increase atorvastatin plasma concentrations and risk of adverse effects. No significant food interactions with amlodipine.
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.
FDA Pregnancy Category X. Amlodipine: No evidence of teratogenicity in animal studies, but limited human data; atorvastatin: contraindicated in pregnancy as HMG-Co A reductase inhibitors are associated with fetal abnormalities, including skeletal and CNS defects. First trimester: Atorvastatin is contraindicated; risk of congenital anomalies. Second/third trimester: Avoid exposure; potential for fetal toxicity. Effective contraception required for women of childbearing potential.
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.
Excreted in human milk: Amlodipine: present in low levels (M/P ratio approximately 1.0); atorvastatin: unknown. Due to potential for serious adverse reactions in nursing infants (e.g., skeletal muscle toxicity from statins), breastfeeding is contraindicated during therapy. Alternative agents preferred.
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.
Contraindicated during pregnancy; therefore, no dosing adjustments recommended. Discontinue therapy immediately if pregnancy is suspected or confirmed. Pharmacokinetic changes during pregnancy may alter drug metabolism, but no dose adjustments are justified due to teratogenic risk.
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.
CADUET is a fixed-dose combination of amlodipine (a calcium channel blocker) and atorvastatin (a statin) used for hypertension and dyslipidemia. Avoid concomitant use with strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole) due to increased statin exposure and risk of myopathy. Monitor liver enzymes before and during therapy, and for muscle symptoms. Use with caution in patients with severe renal impairment. Avoid grapefruit juice as it increases atorvastatin levels.
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 this medication once daily at the same time, with or without food.,Avoid grapefruit and grapefruit juice while taking this medication.,Report unexplained muscle pain, tenderness, or weakness, especially if accompanied by fever or malaise.,Notify your doctor if you become pregnant, plan to become pregnant, or are breastfeeding.,Do not stop taking this medication without consulting your doctor, even if you feel well.
"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 CADUET, 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.. CADUET is a Calcium Channel Blocker + HMG-CoA Reductase Inhibitor that works by Amlodipine: Dihydropyridine calcium channel blocker that inhibits calcium ion influx across cardiac and vascular smooth muscle cell membranes, causing vasodilation and reduced peripheral vascular resistance. Atorvastatin: HMG-Co A reductase inhibitor that competitively inhibits the conversion of HMG-Co A to mevalonate, reducing cholesterol synthesis in the liver.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between FROVA and CADUET 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 CADUET is: CADUET (amlodipine/atorvastatin) is available as tablets of 2.5/10, 2.5/20, 2.5/40, 5/10, 5/20, 5/40, 5/80, 10/10, 10/20, 10/40, and 10/80 mg amlodipine/atorvastatin. Initial dose depends on current antihypertensive and lipid-lowering therapy. Usual starting dose is 5/10 mg orally once daily; titrate at intervals of 2-4 weeks based on blood pressure and LDL-C goals. Maximum daily dose: amlodipine 10 mg; atorvastatin 80 mg.. 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 CADUET 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. CADUET is classified as Category C. FDA Pregnancy Category X. Amlodipine: No evidence of teratogenicity in animal studies, but limited human data; atorvastatin: contraindicated in pregnancy as HMG-CoA reductase inhib. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.