Frova Generic Name & Formulations
Limitations of Use
Confirm diagnosis. Not established for cluster headaches. Do not use for migraine prophylaxis.
Frova Dosage and Administration
Ischemic coronary artery disease (eg, angina pectoris, silent ischemia, history of MI). Coronary artery vasospasm (eg, Prinzmetal's variant angina). Uncontrolled hypertension. Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac conduction pathway disorders. History of stroke or transient ischemic attack (TIA). History of basilar or hemiplegic migraine. Peripheral vascular disease. Ischemic bowel disease. Within 24 hours of other 5-HT1 agonists or ergot-type drugs.
Frova Boxed Warnings
Myocardial Ischemia, Myocardial Infarction, and Prinzmetal Angina
Frova is contraindicated in patients with ischemic or vasospastic coronary artery disease (CAD). Rare reports of serious cardiac adverse reactions, including acute myocardial infarction, have occurred within a few hours following administration.
Prior to treatment, perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (eg, increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD). Do not administer if there is evidence of CAD or coronary artery vasospasm (see Contraindications). For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first Frova dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following administration and consider periodic cardiovascular evaluation in intermittent long-term users of Frova.
Life-threatening disturbances of cardiac rhythm including ventricular tachycardia and ventricular fibrillation leading to death have been reported within a few hours following the administration of 5-HT1 agonists. Discontinue Frova if these disturbances occur.
Frova is contraindicated in patients with Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.
Chest, Throat, Neck and Jaw Pain/Tightness/Pressure
Perform a cardiac evaluation if patients who are at high cardiac risk experience sensations of tightness, pain, and pressure in the chest, throat, neck, and jaw after treatment with Frova.
Frova is contraindicated in patients with CAD or Prinzmetal’s variant angina.
Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities.
Exclude other potentially serious neurological conditions before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with symptoms atypical for migraine. Frova is contraindicated in patients with a history of stroke or transient ischemic attack.
Other Vasospasm Reactions
May cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud’s syndrome.
Rule out a vasospastic reaction before receiving additional Frova doses in patients who experience symptoms or signs suggestive of a non-coronary vasospastic reaction following the use of any 5-HT1 agonist.
Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1 agonists. A causal relationship between visual disorders and the use of 5-HT1 agonists has not been clearly established.
Medication Overuse Headache
Overuse of acute migraine drugs (eg, ergotamine, triptans, opioids, or a combination of drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache).
Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks.
May be necessary to detoxify patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache).
The onset of symptoms usually rapidly occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication.
Discontinue if serotonin syndrome is suspected.
Increase in Blood Pressure
Significant elevations in blood pressure, including hypertensive crisis with acute impairment of organ systems, have been reported in patients treated with 5-HT1 agonists including patients without a history of hypertension.
Monitor blood pressure. Frova is contraindicated in patients with uncontrolled hypertension.
There are no adequate data on the developmental risk associated with the use of Frova in pregnant women.
Women with migraine may be at increased risk of preeclampsia during pregnancy.
Nursing Mother Considerations
There are no data on the presence of frovatriptan or its metabolites in human milk, the effects on the breastfed infant, or the effects of frovatriptan and its metabolites on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Frova and any potential adverse effects on the breastfed infant from Frova or from the underlying maternal condition.
The safety and effectiveness in pediatric patients have not been established. Therefore, Frova is not recommended for use in patients under 18 years of age.
Mean blood concentrations of frovatriptan in elderly patients were 1.5 to 2 times higher than those seen in younger adults.
Hepatic Impairment Considerations
No dosage adjustment is necessary when Frova is given to patients with mild to moderate hepatic impairment. Use caution in patients with severe hepatic impairment.
Mean maximum blood concentrations (Cmax) in patients are achieved approximately 2 to 4 hours after administration of a single oral dose of frovatriptan 2.5 mg. The absolute bioavailability of an oral dose of frovatriptan 2.5 mg in healthy subjects is about 20% in males and 30% in females.
Binding of frovatriptan to serum proteins is low (approximately 15%). The mean steady state volume of distribution of frovatriptan following intravenous administration of 0.8 mg is 4.2 L/kg in males and 3.0 L/kg in females.
Following administration of a single oral dose of radiolabeled frovatriptan 2.5 mg to healthy male and female subjects, 32% of the dose was recovered in urine and 62% in feces. The mean terminal elimination half-life of frovatriptan in both males and females is approximately 26 hours.
Frova Adverse Reactions
Frova Clinical Trials
The efficacy of Frova was established in 4 randomized, double-blind, placebo-controlled, short-term outpatient trials. Patients were randomly assigned to receive doses of frovatriptan from 0.5mg to 40mg. Patients were instructed to treat a moderate to severe headache.
Headache response was defined as a reduction in headache severity from moderate or severe pain to mild or no pain, and was assessed for up to 24 hours after dosing. Maintenance of response was assessed for up to 24 hours post dose.
In all 4 trials, a greater proportion of patients treated with frovatriptan 2.5mg achievd a headache response 2 hours after treatment compared with those treated with placebo, respectively:
Study 1: 42% vs 22% (P <.05)
Study 2: 39% vs 21% (P <.05)
Study 3: 46% vs 27% (P <.001)
Study 4: 37% vs 23% (P <.001)
The lower doses of frovatriptan (0.5mg or 1mg) were not effective at 2 hours. The higher doses of frovatriptan (5mg to 40mg) did not have an added benefit over 2.5mg.
There was a decreased incidence of migraine-associated nausea, photophobia, and phonophobia in patients who received Frova compared with placebo.
Frova Patient Counseling
Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospastic Reactions, and Cerebrovascular Events
Inform patients that Frova may cause serious cardiovascular adverse reactions such as myocardial infarction or stroke, which may result in hospitalization and even death. Instruct patients to be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and instruct them to ask for medical advice when observing any indicative sign or symptoms; serious cardiovascular reactions may occur without warning symptoms. Instruct patients to seek medical advice if they have symptoms of other vasospastic reactions.
Anaphylactic reactions have occurred in patients receiving Frova. Instruct patients to seek immediate medical attention if anaphylactic symptoms develop.
Medication Overuse Headache
Inform patients that use of drugs to treat acute migraines for 10 or more days per month may lead to an exacerbation of headache, and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary).
Inform patients about the risk of serotonin syndrome with the use of Frova or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors.
Advise patients to notify their healthcare provider if they are pregnant or plan to become pregnant.
Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed.