FROVATRIPTAN SUCCINATE
Clinical safety rating
avoidContraindicated (not allowed)
Selective 5-HT1B/1D receptor agonist; causes vasoconstriction of intracranial extracerebral blood vessels and inhibits nociceptive trigeminal nerve transmission.
| Metabolism | Primarily hepatic via CYP1A2; undergoes oxidative metabolism; some contribution from CYP2D6. |
| Excretion | 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. |
| Half-life | 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. |
| Protein binding | Approximately 30% bound to plasma proteins, primarily albumin. Low protein binding suggests minimal displacement interactions. |
| Volume of Distribution | Mean volume of distribution is approximately 2.7 L/kg, indicating extensive extravascular distribution, consistent with its CNS penetration for migraine relief. |
| Bioavailability | Oral bioavailability is approximately 30% due to first-pass metabolism. No other routes are clinically approved; the drug is only available orally. |
| Onset of Action | Oral: Onset of headache relief typically occurs within 30-60 minutes after a single 2.5 mg dose, with maximal effect at 2-4 hours. |
| Duration of Action | Duration of clinical effect (headache relief) is approximately 4-8 hours. Recurrence of headache within 24 hours is possible, and a second dose may be taken after 2 hours if needed, with a maximum of 3 doses per 24 hours. |
| Molecular Weight | 383.46 |
2.5 mg orally once, may repeat after 2 hours if needed; maximum 7.5 mg in 24 hours.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment (CrCl <15 mL/min). For moderate impairment (CrCl 15-29 mL/min), maximum dose 2.5 mg per 24 hours. No adjustment for mild impairment. |
| Liver 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. |
| Pediatric use | Safety and efficacy not established in pediatric patients under 18 years of age. |
| Geriatric use | 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. |
| 1st trimester | Limited human data; based on animal studies, there is potential risk of teratogenicity. Use only if benefit outweighs risk. |
| 2nd trimester | No adequate human studies; animal studies have shown adverse effects. Use with caution. |
| 3rd trimester | May cause uterine contractions and reduce placental blood flow; avoid use near term due to potential for fetal hypoxia. |
Clinical note
Other 5-HT1 agonists can have additive effects Contraindicated in ischemic heart disease and uncontrolled hypertension.
| Placental transfer | Frovatriptan crosses the placenta in animal studies; human data limited but similar transfer is expected due to molecular weight and lipophilicity. |
| Breastfeeding | Frovatriptan is excreted into human breast milk in low concentrations (relative infant dose approximately 3.5%). Consider infant exposure risk; monitor for potential adverse effects such as poor feeding or somnolence. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | 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. |
| Fetal Monitoring | Monitor for signs of fetal distress if used during pregnancy. Assess uterine contractions and fetal heart rate if administered near term. Evaluate maternal blood pressure and heart rate due to potential cardiovascular effects. |
| Fertility Effects | No human studies on fertility. Animal studies (rats) showed no impairment of fertility at doses up to 100 mg/kg/day (200 times MRHD). Theoretical risk of ovarian reserve impact not established. |
■ FDA Black Box Warning
Not recommended for use in patients with risk factors for coronary artery disease (CAD) unless a cardiovascular evaluation confirms absence of CAD.
| Common Effects | Dizziness |
| Serious Effects |
History of ischemic heart disease or coronary artery vasospasm (e.g., Prinzmetal's angina)Uncontrolled hypertensionHemiplegic or basilar migraineSevere hepatic impairment (Child-Pugh C)Concurrent use of ergotamine derivatives or other 5-HT1 agonists within 24 hoursConcurrent use of MAO-A inhibitors
| Precautions | 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. |
| Food/Dietary | 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. |
| Clinical Pearls | 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. |
| Patient Advice | 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. |
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