FROVA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FROVA (FROVA).
Selective serotonin 5-HT1B/1D receptor agonist; causes vasoconstriction of cranial arteries and inhibits trigeminal nerve transmission.
| Metabolism | Hepatic via CYP1A2; primary metabolite is 5-hydroxyfrovatriptan. |
| Excretion | 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. |
| Half-life | Terminal elimination half-life is 26 hours. This prolonged half-life supports once-daily dosing and provides sustained headache relief. |
| Protein binding | Approximately 15% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Volume of distribution (Vd) is approximately 2.4 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 30% due to first-pass metabolism. |
| Onset of Action | Oral: Onset of headache relief occurs within 30–60 minutes after a single 2.5 mg dose. |
| Duration of Action | Duration of effect is approximately 24 hours based on headache recurrence data, allowing once-daily dosing for migraine prophylaxis. |
2.5 mg orally once daily; maximum 5 mg/day.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for GFR ≥30 mL/min; use not recommended for GFR <30 mL/min. |
| Liver impairment | 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). |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment, but monitor for increased sensitivity and renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FROVA (FROVA).
| Breastfeeding | 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. |
| Teratogenic Risk | 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 Black Box Warning
Do not use in patients with ischemic heart disease, coronary artery vasospasm, or other significant cardiovascular conditions.
| Serious Effects |
Ischemic heart disease, coronary artery vasospasm, history of stroke/TIA, peripheral vascular disease, uncontrolled hypertension, hemiplegic or basilar migraine, recent MAOI use, hypersensitivity.
| Precautions | Risk of myocardial ischemia, cerebral hemorrhage, cardiac arrhythmias; serotonin syndrome with concomitant serotonergic drugs; medication overuse headache; severe hepatic impairment. |
Loading safety data…
| Fetal Monitoring | If unintentionally exposed during pregnancy, monitor fetal growth via serial ultrasounds (assess for IUGR), assess for preterm labor signs, and fetal heart rate monitoring if used near term. Monitor maternal blood pressure and signs of serotonin syndrome if used with other serotonergic drugs. |
| Fertility Effects | No specific data on human fertility impairment. Animal studies showed no adverse effects on fertility at exposures up to 100 times the MRHD. However, triptans may theoretically affect ovarian blood flow; use in women attempting conception should be minimized in favor of safer alternatives. |