Migraine, prevention (alternative agent):
Note: Tolerance may develop; consider increasing dose or switching to another calcium channel blocker if tolerance occurs (Schwedt 2022). An adequate trial for assessment of effect is considered to be at least 2 to 3 months at a therapeutic dose (EHF [Steiner 2019]).
Oral: 5 to 10 mg once daily (Steiner 2019; Stubberud 2019; manufacturer's labeling). Incidence of adverse effects may be decreased by allowing 2 consecutive medication-free days each week (Diener 2002).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. However, dosage adjustment is unlikely as flunarizine primarily undergoes hepatic metabolism and minimal urinary excretion.
There are no dosage adjustments provided in the manufacturer's labeling. Flunarizine is hepatically metabolized; use with caution.
Not recommended for use in adults ≥65 years of age due to increased risk of extrapyramidal symptoms.
Extrapyramidal symptoms, progressive fatigue, depression: Discontinue use.
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 5 mg
Not available in the US
Oral: Administer at bedtime.
Note: Not approved in the United States.
Migraine, prevention: Prevention of migraine (with and without aura) in patients with frequent and severe attacks, who have not responded satisfactorily to other treatments, and/or do not tolerate other therapy (due to unacceptable adverse effects).
Limitation of use: Not indicated for treatment of acute attacks.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not always defined.
Central nervous system: Drowsiness (20%), anxiety, depression, dizziness, extrapyramidal reaction, fatigue, insomnia, motor dysfunction, sedation, sleep disorder, vertigo
Dermatologic: Skin rash
Endocrine & metabolic: Weight gain (15%), galactorrhea, increased serum prolactin, menstrual disease
Gastrointestinal: Heartburn, increased appetite, nausea, stomach pain, vomiting, xerostomia
Neuromuscular & skeletal: Myalgia, weakness
Hypersensitivity to flunarizine or any component of the formulation; history of depression; preexisting symptoms of Parkinson disease or other extrapyramidal disorders.
Concerns related to adverse effects:
• CNS effects: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving). Rarely, progressive fatigue may occur during therapy; monitor for fatigue symptoms. Discontinue therapy with progressively worsening fatigue.
• Depression: May precipitate depression; greater risk in younger patients. Monitor for depressive symptoms and discontinue use if depressive symptoms occur.
• Endocrine effects: Galactorrhea (rare) has been reported in female patients during the first 2 months of therapy; usually resolves with discontinuation of therapy. Mild but significant increase in serum prolactin levels and menstrual irregularities have been observed with use.
• Extrapyramidal symptoms: May produce extrapyramidal symptoms in individuals with no prior history of neurological deficits; monitor for symptoms (may require discontinuation); effects are usually reversible upon discontinuation of therapy. Risk is increased in older adults.
Disease-related concerns:
• Hepatic impairment: Undergoes hepatic metabolism; use with caution.
Other warnings/precautions:
• Appropriate use: Discontinue use if inadequate response after 3 months of therapy. Closely monitor for adverse effects (eg, CNS effects), including in patients treated for >6 months; discontinue therapy with onset of adverse effects. Risk for adverse effects may be decreased by allowing 2 consecutive medication-free days each week. Not indicated for treatment of acute migraine attacks.
Substrate of CYP2D6 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Antihypertensive Agents: Flunarizine may enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Flunarizine. Risk C: Monitor therapy
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Fosphenytoin: May decrease the serum concentration of Flunarizine. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Phenytoin: May decrease the serum concentration of Flunarizine. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valproate Products: May decrease the serum concentration of Flunarizine. Risk C: Monitor therapy
Adverse events have been observed in animal reproduction studies.
It is not known if flunarizine is excreted into breast milk. Breast-feeding is not recommended by the manufacturer.
Extrapyramidal, depressive, and/or fatigue symptoms (at regular intervals).
Flunarizine is a selective calcium channel blocker that prevents cellular calcium overload by reducing excessive transmembrane calcium influx; also has antihistamine properties. Has greater effect on decreasing the frequency of migraine attacks than on decreasing the severity or duration of attacks.
Absorption: Well absorbed
Distribution: Vd: Mean: 43.2 L/kg
Protein binding: 90%
Metabolism: Hepatic: N-oxidation, aromatic hydroxylation
Half-life: Variable; Alpha: ~2.4 to 5.5 hours (single dose); Beta: ~4 days (single dose), ~19 days (multidose)
Time to peak, plasma: 2 to 4 hours
Excretion: Feces (<6% at 48 hours); urine (minimal)
