Drug Interactions
Appears to be metabolized principally via CYP1A2.
Does not inhibit CYP1A2, 2C9, 2C19, 2D6, 2E1, or 3A4 or MAO isoenzymes in vitro; does not induce drug metabolizing enzymes. Pharmacokinetic interaction with drugs metabolized by these isoenzymes unlikely.
Drugs Affecting Hepatic Microsomal Enzymes
Potential pharmacokinetic interaction (increased plasma frovatriptan concentrations) with concomitant use of CYP1A2 inhibitors; however, effects not considered clinically relevant.
Specific Drugs
| Drug |
Interaction |
Comments |
| Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) or SNRIs (e.g., duloxetine, venlafaxine) |
Potentially life-threatening serotonin syndrome
Potential increase in blood frovatriptan concentrations with concomitant fluvoxamine administration |
Observe carefully if used concomitantly, particularly during treatment initiation, dosage increases, or when another serotonergic agent is initiated
No dosage adjustment required if fluvoxamine is used concomitantly |
| Ergot alkaloids (e.g., ergotamine, dihydroergotamine, methysergide) |
Additive vasospastic effects |
Use within 24 hours contraindicated |
| 5-HT1 receptor agonists |
Additive vasospastic effects |
Use within 24 hours contraindicated |
| Oral contraceptives |
Possible increased plasma concentrations of frovatriptan |
No dosage adjustment required |
| Propranolol |
Possible increased plasma concentrations of frovatriptan |
No dosage adjustment required |
Pharmacokinetics
Absorption
Bioavailability
Incompletely absorbed from GI tract; absolute bioavailability of 20 and 30% in males and females, respectively.
Peak plasma concentrations attained approximately 2–4 hours after oral administration.
Food
Food does not affect bioavailability but may delay time to peak plasma concentration by 1 hour.
Distribution
Extent
Distributes into cellular fraction of blood, principally erythrocytes (approximately 60% reversibly bound).
Animal studies indicate limited capacity to cross blood-brain barrier.
Distributed into milk in rats; not known whether distributed into milk in humans.
Plasma Protein Binding
Approximately 15%.
Elimination
Metabolism
Appears to be metabolized principally via CYP1A2 to numerous metabolites, including desmethyl frovatriptan, which exhibits lower affinity for 5-HT1B/1D receptors compared with frovatriptan.
Elimination Route
Excreted in urine (32%) and feces (62%) as unchanged drug and metabolites.
Half-life
Approximately 26 hours.
Special Populations
In patient with mild to moderate hepatic impairment, AUC is twofold higher than in healthy individuals; pharmacokinetics not studied in patients with severe hepatic impairment.
In geriatric patients, AUC is 1.5- to 2-fold higher than in younger adults; half-life and time to peak plasma concentrations unchanged.
Stability
Storage
Oral
Tablets
25°C (may be exposed to 15–30°C). Protect from moisture and light.
Actions
- Binds with high affinity to 5-HT1B and 5-HT1D receptors.
- Structurally distinct from, but pharmacologically related to, other selective 5-HT1B/1D receptor agonists (e.g., almotriptan, eletriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan).
- Precise mechanism of action not established; may ameliorate migraine through selective constriction of certain intracranial blood vessels, inhibition of neuropeptide release, and reduced transmission in trigeminal pain pathway.
Advice to Patients
- Importance of immediately informing clinician if tightness, pain, pressure, or heaviness in chest, throat, jaw, or neck occurs and of not taking frovatriptan again until evaluated by clinician.
- Importance of taking frovatriptan exactly as prescribed.
- Importance of providing patient a copy of manufacturer’s patient information.
- Risk of dizziness or fatigue; importance of exercising caution when driving or operating machinery.
- Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).
- Importance of informing patients of risk of serotonin syndrome with concurrent use of frovatriptan and an SSRI or SNRI. Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.
- Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
- Importance of informing patients of other important precautionary information. (See Cautions.)
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