Cinnarizine- and flunarizine-associated movement disorder: a literature review

Jamir Pitton Rissardo,Ana Letícia Fornari Caprara

doi:10.1186/s41983-020-00197-w

Jamir Pitton Rissardo, Ana Letícia Fornari Caprara

Open Access

https://doi.org/10.1186/s41983-020-00197-w

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Abstract

IntroductionCinnarizine (CNZ) and flunarizine (FNZ) belong to the calcium channel blockers class of medication.Main textThe aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of CNZ/FNZ-associated movement disorder (MD). Relevant reports in six databases were identified and assessed by two reviewers without language restriction. One hundred and seventeen reports containing 1920 individuals who developed a CNZ/FNZ-associated MD were identified. The MD encountered were 1251 parkinsonism, 23 dyskinesias, 11 akathisia, 16 dystonia, and 5 myoclonus, and in the group not clearly defined, 592 extrapyramidal symptoms, 19 tremors, 2 bradykinesia, and 1 myokymia. The predominant sex was female with a percentage of 72.69% (466/641). The mean age was 74.49 (SD, 7.88) years. The mean CNZ dose was 148.19 mg (SD, 42.51) and for the FNZ dose, 11.22 mg (5.39). The mean MD onset and recovery were 1.83 years (SD, 1.35) and 3.71 months (SD, 1.26). In the subgroup of subjects that had improvement of the symptoms, the complete recovery was achieved within 6 months of the drug withdrawal in almost all subjects (99%). The most common management was drug withdrawal. A complete recovery was observed in 93.77% of the patients (437/466).ConclusionsCNZ/FNZ-associated MD was extensively reported in the literature. Parkinsonism was the most well described. Myoclonus (MCL) was the poorest described MD with missing data about the neurological examination and electrodiagnostic studies. The knowledge of this disorder probably can contribute to the understanding of the other drug-induced MDs.

Highlights

Cinnarizine (CNZ) and flunarizine (FNZ) belong to the calcium channel blockers class of medication
Cases that had more than one factor contributing to the movement disorder (MD) were evaluated based on the probability of the event occurrence based on the Naranjo algorithm
For the years 1980 and 2019, a total of 117 reports containing 1920 individuals who developed a movement disorder associated with CNZ/FNZ were identified from 27 countries (Table 1) [3,4,5, 12,13,14,15, 20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129]

Summary

Introduction

Cinnarizine (CNZ) and flunarizine (FNZ) belong to the calcium channel blockers class of medication. Cinnarizine (CNZ) and flunarizine (FNZ) belong to the calcium channel blockers family (Fig. 1). In this context, CNZ was first synthesized in 1955 by chemistries of the Janssen Pharmaceutica in attempts to develop a new antihistamine drug [1]; animal studies showed that CNZ inhibits vascular smooth muscle contraction, and this action occurs especially in the intracranial vessels [2]. FNZ showed an efficacy of 2.5 to 15 times stronger than CNZ [6] It was first marketed in Europe around the 1980s about 10 years after the release of CNZ [3]. Spain among the European countries was one of the first in which FNZ was available [6] and probably the country with the greatest number of CNZ/FNZ prescriptions; in 1985, approximately 5% of the Spanish population over sixty were on CNZ treatment [3]

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