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Clinical data
Trade names Sibelium
AHFS/Drugs.com Micromedex Detailed Consumer Information
  • C
Routes of
ATC code N07CA03 (WHO)
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Protein binding >99%
Metabolism Mainly CYP2D6
Metabolites ≥15
Biological half-life 5–15 hrs (single dose)
18–19 days (multiple doses)
Excretion Faeces, <1% urine
Synonyms 1-[bis(4-fluorophenyl)methyl]-4-cinnamyl-piperazine
CAS Number 52468-60-7 YesY
PubChem (CID) 941361
DrugBank DB04841 YesY
ChemSpider 819216 YesY
KEGG D07971 YesY
ECHA InfoCard 100.052.652
Chemical and physical data
Formula C26H26F2N2
Molar mass 404.495 g/mol
3D model (Jmol) Interactive image
Melting point 251.5 °C (484.7 °F) (dihydrochloride)

Flunarizine (trade name Sibelium and many others) is a drug classified as a calcium antagonist.[1] It is effective in the prophylaxis of migraine,[2] occlusive peripheral vascular disease, vertigo of central and peripheral origin,[3] and as an adjuvant in the therapy of epilepsy. It has been shown to significantly reduce headache frequency and severity in both adults and children.

Flunarizine is not available by prescription in the U.S. or Japan. It was discovered at Janssen Pharmaceutica in 1968.


Flunarizine is contraindicated in patients with depression, in the acute phase of a stroke, and in patients with extrapyramidal symptoms or Parkinson's disease.[4] It is also contraindicated in hypotension, heart failure and arrhythmia.

Side effects

Common side effects include drowsiness (20% of patients), weight gain (10%), as well as extrapyramidal effects and depression in elderly patients.[3]


The effects of other sedating drugs and alcohol, as well as antihypertensives, can be increased. No relevant pharmacokinetic interactions have been described.[3][4]


Mechanism of action

Flunarizine is a non-selective calcium antagonist with moderate other actions including antihistamine, serotonin receptor blocking and dopamine D2 blocking activity. Compared to other calcium channel blockers such as dihydropyridine derivatives, verapamil and diltiazem, flunarizine has low affinity to voltage-dependent calcium channels. It has been theorised that it may act not by inhibiting calcium entry into cells, but rather by an intracellular mechanism such as antagonising calmodulin, a calcium binding protein.[3]


Flunarizine is well absorbed (>80%) from the gut and reaches maximal blood plasma concentrations after two to four hours, with more than 99% of the substance bound to plasma proteins. It readily passes the blood–brain barrier. When given daily, a steady state is reached after five to eight weeks. Concentrations in the brain are about ten times higher than in the plasma.[3][4]

The substance is metabolised in the liver, mainly by the enzyme CYP2D6. At least 15 different metabolites are described, including (in animals) N-desalkyl and hydroxy derivatives and glucuronides. Less than 1% is excreted in unchanged form, and the main excretion path is via bile and faeces. Elimination half life varies widely between individuals and is about 5 to 15 hours after a single dose, and 18 to 19 days on average when given daily.[3][4]


Flunarizine may help to reduce the severity and duration of attacks of paralysis associated with the more serious form of alternating hemiplegia, as well as being effective in rapid onset dystonia-parkinsonism (RDP). Both these conditions share a mutation in the ATP13A gene.[5]


  1. Fagbemi, O; Kane, KA; McDonald, FM; Parratt, JR; Rothaul, AL (1984). "The effects of verapamil, prenylamine, flunarizine and cinnarizine on coronary artery occlusion-induced arrhythmias in anaesthetized rats". British Journal of Pharmacology. 83 (1): 299–304. doi:10.1111/j.1476-5381.1984.tb10146.x. PMC 1987188Freely accessible. PMID 6487894.
  2. Amery, WK (1983). "Flunarizine, a calcium channel blocker: A new prophylactic drug in migraine". Headache. 23 (2): 70–4. doi:10.1111/j.1526-4610.1983.hed2302070.x. PMID 6343298.
  3. 1 2 3 4 5 6 Dinnendahl, V, Fricke, U, eds. (2012). "Arzneistoff-Profile" (in German). 2 (26 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
  4. 1 2 3 4 Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  5. ATP13A mutation,and response to flunarizine
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