Frova (frovatriptan succinate)

Available as frovatriptan succinate; dosage is expressed in terms of frovatriptan.

Frovatriptan is available in a tablet formulation for oral administration.

Frovatriptan should be administered with fluids.

Tablets should be stored at 20-25degreesC with excursions permitted between 15-30degreesC; protect from moisture.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

5-Ht1d Agonists/Ergot Alkaloids

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The 5-HT1D agonists and ergot alkaloids can produce vasospastic reactions.

CLINICAL EFFECTS: Concurrent therapy may produce additive vasospastic effects.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer states that sumatriptan should not be used within 24 hours of an ergotamine-containing or ergotamine-like medication (such as dihydroergotamine or methysergide).(1,2) The Australian(3) and UK(4,5) manufacturers state that 24 hours should elapse before sumatriptan is administered following an ergotamine-containing preparation and 6 hours should elapse before an ergotamine-containing preparation is administered following sumatriptan. The US manufacturer states that zolmitriptan should not be used within 24 hours of an ergotamine-containing or ergotamine-like medication.(6) The UK manufacturer states that zolmitriptan should not be used within 6 hours of an ergotamine-containing or ergotamine-like medication.(7) The The Australian manufacturer states that 24 hours should elapse before zolmitriptan is administered following an ergotamine-containing preparation and 6 hours should elapse before an ergotamine-containing medication is administered following zolmitriptan.(8) The US manufacturer states that the use of rizatriptan within 24 hours of an ergotamine-containing or ergot-type medication is contraindicated.(9) The US manufacturer states that the use of naratriptan within 24 hours of an ergotamine-containing or ergot-type medication is contraindicated.(10) The Australian manufacturer states that concurrent use of naratriptan and ergotamine or ergotamine derivatives is not recommended.(11) The US manufacturer states that the use of eletriptan within 24 hours of an ergotamine-containing or ergot-type medication is contraindicated.(12) The UK manufacturer states that the use of eletriptan within 24 hours of an ergotamine-containing or ergot-type medication is not recommended.(13)

DISCUSSION: Because of the theoretical risk of additive vasospastic effects, the US manufacturer states that the use of sumatriptan within 24 hours of an ergotamine-containing or ergotamine-like medication is contraindicated.(1,2) The Australian(3) and UK(4,5) manufacturer states that 24 hours should elapse before sumatriptan is administered following an ergotamine-containing preparation and 6 hours should elapse before an ergotamine-containing medication is administered following sumatriptan. Although the pharmacokinetics of zolmitriptan were not affected by ergotamine, the UK manufacturer of zolmitriptan recommends that 6 hours should elapse between the administration of zolmitriptan and an ergotamine preparation.(7) The US manufacturer of zolmitriptan states under contraindications that zolmitriptan should not be used within 24 hours of an ergotamine-containing or ergot-type medication.(6) The Australian manufacturer states that 24 hours should elapse before zolmitriptan is administered following an ergotamine-containing preparation and 6 hours should elapse before an ergotamine-containing medication is administered following zolmitriptan.(8) Because of the additive risk of prolonged vasospastic reactions, the manufacturers of rizatriptan(9) and naratriptan(10) in the US state that the use of ergotamine-containing or ergot-type medications and these agents is contraindicated. The Australian manufacturer states that concurrent use of naratriptan and ergotamine or ergotamine derivatives is not recommended.(11) Administration of oral ergotamine one and two hours after eletriptan resulted in additive increases in blood pressure.(13)

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Ischemic coronary artery disease (e.g., angina pectoris, history of myocardial infarction, documented silent ischemia), coronary artery vasospasm (e.g., Prinzmetal variant angina), or uncontrolled hypertension.

*Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

*Cerebrovascular syndromes (e.g., history of stroke, transient ischemic attack, or hemiplegic or basilar migraine), peripheral vascular disease, or ischemic bowel disease.

*Recent (i.e., within 24 hours) treatment with another 5-HT1 receptor agonist or an ergotamine-containing or ergot-type drug.

*Known hypersensitivity to frovatriptan; angioedema and anaphylaxis reported.

• Acute myocardial infarction
• Angina
• Cerebral ischemia
• Cerebrovascular accident
• Coronary artery disease
• Coronary artery spasm
• Hemiplegic migraine
• Ischemic bowel disease
• Myocardial ischemia
• Peripheral vascular disease
• Prinzmetal angina
• Serotonin syndrome
• Severe uncontrolled hypertension

• Hypertension
• Tachyarrhythmia

• Raynaud's phenomenon

The most common adverse effects occurring in >=2% of patients receiving frovatriptan and more frequently than with placebo include dizziness, fatigue, headache, paresthesia, flushing, dry mouth, hot or cold sensation, skeletal pain, dyspepsia, and chest pain.

More Frequent

• Chest pain

Less Frequent

• Anaphylaxis
• Angioedema
• Peripheral ischemia

Rare or Very Rare

• Acute myocardial infarction
• Seizure disorder
• Serotonin syndrome
• Ventricular fibrillation
• Ventricular tachycardia

More Frequent

• Bone pain
• Dizziness
• Dyspepsia
• Fatigue
• Flushing
• Headache disorder
• Paresthesia
• Sensation of cold
• Sensation of warmth
• Xerostomia

Less Frequent

• Acute abdominal pain
• Diarrhea
• Drowsy
• Dysesthesia
• Hyperhidrosis
• Hypoesthesia
• Insomnia
• Jaw pain
• Nausea
• Neck pain
• Palpitations
• Rhinitis
• Sinusitis
• Sore throat
• Symptoms of anxiety
• Tinnitus
• Visual changes
• Vomiting

Rare or Very Rare

• Acute cognitive impairment
• Agitation
• Arthralgia
• Back pain
• Bullous dermatitis
• Constipation
• Dysphagia
• Dyspnea
• Earache
• Euphoria
• Flatulence
• Hyperesthesia
• Hypertension
• Hyperventilation
• Laryngitis
• Medication overuse headache
• Myalgia
• Ocular pain
• Pharyngitis
• Pruritus of skin

No enhanced messaging available.

Safety and efficacy of frovatriptan have not been established in children younger than 18 years of age.

Frovatriptan produced embryofetal lethality, fetal abnormalities, and reduced embryofetal growth in animal studies at doses greater than those used clinically. There are no adequate and well-controlled studies of the developmental risk associated with frovatriptan therapy in pregnant women.

Frovatriptan and/or its metabolites are distributed into milk in rats; it is not known whether frovatriptan is distributed into human milk, its effects on the breastfed infant, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for frovatriptan and any adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

No dosage adjustment is necessary in geriatric patients.

Plasma concentrations of frovatriptan are substantially (1.5- to 2-fold) higher in geriatric patients than in younger adults. No adjustment in frovatriptan dosage appears to be necessary in geriatric patients.