Flunarizine (United States: Not available): Drug information

For additional information see "Flunarizine (United States: Not available): Patient drug information"

For abbreviations, symbols, and age group definitions show table

Pharmacologic Category

Calcium Channel Blocker

Dosing: Adult

Migraine, prevention

Migraine, prevention (alternative agent):

Note: Tolerance may develop; consider increasing dose or switching to another calcium channel blocker if tolerance occurs (Ref). An adequate trial for assessment of effect is considered to be at least 2 to 3 months at a therapeutic dose (Ref).

Oral: 5 to 10 mg once daily (Ref). Incidence of adverse effects may be decreased by allowing 2 consecutive medication-free days each week (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

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.

Dosing: Liver Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. Flunarizine is hepatically metabolized; use with caution.

Dosing: Adjustment for Toxicity: Adult

Extrapyramidal symptoms, progressive fatigue, depression: Discontinue use.

Dosing: Older Adult

Not recommended for use in adults ≥65 years of age due to increased risk of extrapyramidal symptoms.

Adverse Reactions

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

Contraindications

Hypersensitivity to flunarizine or any component of the formulation; history of depression; preexisting symptoms of Parkinson disease or other extrapyramidal disorders.

Warnings/Precautions

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.

Product Availability

Not available in the US

Generic Equivalent Available: US

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Generic: 5 mg

Administration: Adult

Oral: Administer at bedtime.

Use: Labeled Indications

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.

Metabolism/Transport Effects

Substrate of CYP2D6 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;

Drug Interactions

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 drug interactions program by clicking on the “Launch drug interactions program” link above.

Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Antihypertensive Agents: Flunarizine may increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor

Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification

Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification

Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor

CarBAMazepine: May decrease serum concentration of Flunarizine. Risk C: Monitor

Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification

Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

CNS Depressants: May increase CNS depressant effects of Flunarizine. Risk X: Avoid

Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor

Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification

Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor

Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Fosphenytoin: May decrease serum concentration of Flunarizine. Risk C: Monitor

Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor

Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid

Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid

Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid

Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Phenytoin: May decrease serum concentration of Flunarizine. Risk C: Monitor

Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor

Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor

Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects 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 increase sedative effects of ROPINIRole. Risk C: Monitor

Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor

Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid

Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Valproic Acid and Derivatives: May decrease serum concentration of Flunarizine. Risk C: Monitor

Reproductive Considerations

In general, preventive treatment for migraine in patients trying to become pregnant should be avoided. Options for patients planning a pregnancy should be considered as part of a shared decision-making process. Nonpharmacologic interventions should be considered initially. When needed, preventive treatment should be individualized considering the available safety data and needs of the patient should pregnancy occur. A gradual discontinuation of preventive medications is generally preferred when the decision is made to stop treatment prior to conception (ACOG 2022; AHS [Ailani 2021]).

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies.

In general, preventive treatment for migraine should be avoided during pregnancy. Options for pregnant patients should be considered as part of a shared decision-making process. Nonpharmacologic interventions should be considered initially. When needed, preventive treatment should be individualized considering the available safety data, the potential for adverse maternal and fetal events, and needs of the patient (ACOG 2022; AHS [Ailani 2021]). If preventive therapy is needed, agents other than flunarizine are preferred (CHS [Pringsheim 2012]).

Breastfeeding Considerations

It is not known if flunarizine is present in breast milk.

Breastfeeding is not recommended by the manufacturer. In general, preventive treatment for migraine in lactating patients should be avoided. When needed, therapy should be individualized considering the available safety data and needs of the patient (AHS [Ailani 2021]). If preventive therapy is needed, agents other than flunarizine are preferred (CHS [Pringsheim 2012]).

Monitoring Parameters

Extrapyramidal, depressive, and/or fatigue symptoms (at regular intervals).

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Well absorbed

Distribution: V_d: 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)

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Sibelium;
(AR) Argentina: Coromert | Niflucan;
(AT) Austria: Amalium;
(AU) Australia: Sibelium;
(BD) Bangladesh: Imigra | Sibelium;
(BE) Belgium: Flunarimed | Flunatop | Sibelium;
(BG) Bulgaria: Flunarizin | Sibelium;
(BR) Brazil: Flunarin;
(CH) Switzerland: Sibelium;
(CL) Chile: Sibelium;
(CN) China: Flunarizine | Flunarizine hydrochloride | Fu rui lin | Long bai li | Olibowk | Sibelium | Xi bi ling;
(CO) Colombia: Fluidex | Flunarizina | Flunik | Flunimed | Sibelium;
(CZ) Czech Republic: Sibelium;
(DE) Germany: Flunarizin | Flunavert | Natil N | Sibelium;
(DO) Dominican Republic: Sibeliun;
(EC) Ecuador: Sibelium;
(EE) Estonia: Sibelium;
(EG) Egypt: Flunarizine hydrochloride | Sibelium;
(ES) Spain: Flurpax;
(GR) Greece: Sibelium;
(HK) Hong Kong: Fludan | Funasin | Poli Flunarin | Sibelium | Suzin | Vanid;
(IE) Ireland: Sibelium;
(IN) India: Migrecure | Nomigrain;
(IT) Italy: Flugeral | Flunagen | Fluxarten | Gradient | Issium | Sibelium | Vasculene;
(JO) Jordan: Sibelium;
(KE) Kenya: Hefunar;
(KR) Korea, Republic of: Ceronate | Flarizin | Flurizine | Funazin | Headache | Hefen | Hepen | Naripen | Nariven | Nazina | Salium | Sarium | Sibelium;
(KW) Kuwait: Sibelium;
(LB) Lebanon: Sibelium;
(LT) Lithuania: Flunarizin | Flunarizin acis | Flunarizin CT | Sibelium;
(LU) Luxembourg: Sibelium;
(LV) Latvia: Flunarizin | Flunarizin acis | Flunatop | Natil N | Sibelium;
(MX) Mexico: Axilin | Fasolan | Sibelium;
(MY) Malaysia: Fludan | Flunarizine | Sibelium;
(NL) Netherlands: Flunarizine | Sibelium;
(NO) Norway: Flugeral | Flunarizin acis | Flunarizin CT;
(PH) Philippines: Flumig | Sibelium;
(PK) Pakistan: Luner | Migram | Polyzine | Sibelium;
(PL) Poland: Sibelium;
(PT) Portugal: Sibelium | Zinasen;
(QA) Qatar: Sibelium;
(SA) Saudi Arabia: Apo-flunarizine | Sibelium;
(SG) Singapore: Poli Flunarin | Sibelium;
(SK) Slovakia: Sibelium;
(SR) Suriname: Flunatop;
(TH) Thailand: Bizerol | Cebrium | Cedelate | Cerebium | Cerebrium | Floxin | Flubelin | Flubelium | Flubilium | Flucazin | Flucilium | Fludan | Fluna | Flunacap | Flunadian | Flunagen | Flunamed | Flunarium | Flunarizine | Flunaza | Flunazine | Flurin | Flurizine | Fnz | Fucimed | Goose Nazine | Hexilium | Himbelium | Inrizine | Liberal | Medilium | Morizin | Nuzine | Pharizine | Poli Flunarin | Rizena | Sana | Sarina | Sezine | Sibelium | Sifluna | Silium | Simoyiam | Sinada | Sinazine | Sinozine | Sinuzine | Sirizine | Sobelin | Sobexin | Sovelium | Tenmed | Vanid | Vertilium | Zeflow | Zelium;
(TR) Turkey: Sibelium;
(TW) Taiwan: Flunazon | Flurpax | Funasin | S.N.A | Sibelium | Sufuni | Suzin;
(UY) Uruguay: Sibelium;
(VE) Venezuela, Bolivarian Republic of: Flunarizina | Sibelium;
(VN) Viet Nam: Fluzinstad | Hagizin | Sarariz | Serapid | Sibetab | Upaforu;
(ZA) South Africa: Sibelium

Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society consensus statement: update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021-1039. doi:10.1111/head.14153 [PubMed 34160823]
American College of Obstetricians and Gynecologists (ACOG). ACOG committee on clinical practice guidelines–obstetrics. Headaches in pregnancy and postpartum: ACOG clinical practice guideline no. 3. Obstet Gynecol. 2022;139(5):944-972. doi:10.1097/AOG.0000000000004766 [PubMed 35576364]
Diener HC, Matias-Guiu J, Hartung E, et al. Efficacy and tolerability in migraine prophylaxis of flunarizine in reduced doses: a comparison with propranolol 160 mg daily. Cephalalgia. 2002;22(3):209-221. doi:10.1046/j.1468-2982.2002.t01-1-00309.x [PubMed 12047461]
Flunarizine [product monograph]. Vaughan, Ontario, Canada: AA Pharma Inc; April 2021.
Kariya S, Isozaki S, Uchino K, et al. Oxidative metabolism of flunarizine and cinnarizine by microsomes from B-lymphoblastoid cell lines expressing human cytochrome P450 enzymes. Biol Pharm Bull. 1996;19(11):1511-1514. [PubMed 8951176]
Pringsheim T, Davenport W, Mackie G, et al; Canadian Headache Society Prophylactic Guidelines Development Group. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci. 2012;39(2 suppl 2):S1-S59. [PubMed 22683887]
Refer to manufacturer's labeling.
Schwedt TJ, Garza I. Preventive treatment of episodic migraine in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 21, 2022
Steiner TJ, Jensen R, Katsarava Z, et al. Aids to management of headache disorders in primary care (2nd edition): on behalf of the European Headache Federation and Lifting the Burden: the Global Campaign against Headache. J Headache Pain. 2019;20(1):57. doi:10.1186/s10194-018-0899-2 [PubMed 31113373]
Stubberud A, Flaaen NM, McCrory DC, Pedersen SA, Linde M. Flunarizine as prophylaxis for episodic migraine: a systematic review with meta-analysis. Pain. 2019;160(4):762-772. doi:10.1097/j.pain.0000000000001456 [PubMed 30699098]

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Flunarizine (United States: Not available): Drug information