Indian J Otolaryngol Head Neck Surg
(November 2019) 71(Suppl 2):S1060–S1068; DOI 10.1007/s12070-017-1120-7
ORIGINAL ARTICLE
Cinnarizine: A Contemporary Review
Milind Vasant Kirtane1 • Anita Bhandari2 • Prashant Narang3 • Ravi Santani3
Received: 27 October 2016 / Accepted: 4 April 2017 / Published online: 25 April 2017
 Association of Otolaryngologists of India 2017
Abstract Cinnarizine, is approved for nausea, vomiting,
motion sickness, inner ear disorders and is considered as
first-line pharmacotherapy for management of vertigo. It
acts by anti-vasoconstrictor activity, reducing blood
viscosity and reducing nystagmus in labyrinth. Lack of
adequate literature on clinical evidence of cinnarizine and
its combination (dimenhydrinate) in vertigo management
prompted this review. A specific MEDLINE literature
search strategy was designed combining Medical Subject
Headings, free-text keywords (like cinnarizine and vertigo)
using Boolean operators (1970–2016) for clinical studies,
clinical reviews and meta-analyses of cinnarizine. Analyses
of studies validated cinnarizine’s efficacy in peripheral and
central vertigo versus placebo or other therapies, and was
well-tolerated by the patients recruited across different
studies. Cinnarizine and/ or its combinations are favorable
in management of vestibular disorders wherein cinnarizine
acts predominantly peripherally on labyrinth and
dimenhydrinate acts centrally on vestibular nuclei and
associated centers in brainstem. Combination therapy of
cinnarizine and/ or its combinations demonstrated a better
safety profile than either of the mono-components, offering
a viable therapeutic option in vertigo management.
& Ravi Santani
rsantani@its.jnj.com
1 of mainly clinical studies of cinnarizine and combination
Department of Otolaryngology, P.D. Hinduja National
Hospital and Medical Research Centre, Mumbai,
Maharashtra, India
2
Vertigo and Ear Clinic, Jaipur, Rajasthan, India
3 collected for the period from 1970 to 2016. Data in
Medical Affairs Department, Janssen India, Arena Space,
Behind Majas Depot, Off JVLR, Jogeshwari East, Mumbai,
Maharashtra 400060, India
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Keywords Cinnarizine
Vertigo
Dimenhydrinate

Drug combinations
Introduction
Cinnarizine is a well-established anti-vertigo drug initially
synthesized as an anti-histamine [1]. It is the mainstay
therapy for vestibular disorders [2], approved for nausea,
vomiting, motion sickness, vertigo and tinnitus associated
with Ménière’s disease and other middle ear disorders, as a
nootropic drug (memory and cognitive function enhancer)
and as adjunct therapy for peripheral arterial disease [3].
Betahistine, prochlorperazine and dimenhydrinate are also
used to treat vertigo (Table 1). Cinnarizine and/ or its
combination is approved in India for the management of
vertigo [4]. Limited publications of cinnarizine ?
dimenhydrinate have been reported in last two decades.
This contemporary review aims to evaluate the role of
cinnarizine and/ or its combinations in vertigo.
Methods
A literature search was done on MEDLINE. The search
strategy included Medical Subject Headings and free-text
keywords (cinnarizine, dimenydrinate and vertigo) using
Boolean operators (‘OR’ and ‘AND’). English publications
therapy (cinnarizine ? dimenhydrinate), clinical reviews,
meta-analysis involving cinnarizine and guidelines for
management of vertigo in various conditions were
prescribing information leaflets, manufacturing as well as
labelling data were also incorporated.
Indian J Otolaryngol Head Neck Surg (November 2019) 71(Suppl 2):S1060–S1068 S1061

Table 1 Mechanism of action of most commonly used drugs in vertigo management

Drug Mechanism of action

Betahistine [2] Antagonist of H3R; partial, weak agonist of H1R and H2R
Cinnarizine [2] L-type Ca2? channel blocker, H1 anti-histaminic action (slight), potential antagonist of nicotinic AChR,
pressure-sensitive potassium channel blocker
Dimenhydrinate [2] Antagonist of H1R and AChR
Prochlorperazine [32] Dopaminergic antagonist-acts at chemoreceptor trigger zone reducing neural impulses to vomiting center;
cannot prevent vertigo/motion sickness but useful in treating accompanying nausea and vomiting
AChR acetyl choline receptor, H3R histamine H3 receptor, H1R histamine H1 receptor, H2R histamine H2 receptor

Mechanism of Action nausea and vomiting in a range of conditions including

Cinnarizine, developed as an anti-histamine, subsequently
manifested a number of pharmacological effects, most
significantly: labyrinthine suppressant action and peripheral
anti-vasoconstrictive effects [5]. Cinnarizine inhibits smooth
muscle cell contraction in the vasculature by blocking L-and
T-type voltage-gated calcium channel. It is also known to
bind to histamine H1 receptors, muscarinic (acetyl choline)
receptors and dopamine D2 receptors [6]. Thus, the
mechanism of action of cinnarizine is multimodal (Fig. 1).
Insufficient cerebral blood circulation has been hypothesized
to cause ‘vertiginous symptoms’ like tinnitus, dizziness,
transient ischemic attacks. Cinnarizine’s anti-vasoconstrictive
and protective action against hyperviscosity of blood along
with its peripheral anti-ischemic action may be helpful in
improving blood flow thus playing an important role in
various therapeutic indications [7].
Anti-vasoconstrictor Action
Vasodilators can cause relaxation irrespective of whether
the altered Ca2? dependent tone is caused by intrinsic
(myogenic) or extrinsic (vasoconstrictor) activity.

Fig. 1 Mechanism of action of cinnarizine. RBC red blood cell

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S1062 Indian J Otolaryngol Head Neck Surg (November 2019) 71(Suppl 2):S1060–S1068
Cinnarizine, on the other hand, has no direct vasodilatory
action and does not directly interfere with the potential of
smooth muscle cells to develop tone. Instead it selectively
inhibits spasmogen-stimulated Ca2? influx and thus
differentiates increased Ca2? influxes in response to
vasoconstrictors as opposed to those caused by intrinsic
myogenic changes in membrane potential [8] and hence, is
described as an anti-vasoconstrictor.
Action on Blood Viscosity
Increased blood viscosity is an important factor in reducing
blood flow in patients with ischemic diseases and
intermittent claudication [9]. Historical data have shown
that cinnarizine decreases blood viscosity in patients with
ischemic diseases. Many studies have proposed that the
ability of cinnarizine to reduce blood viscosity is attributed
to its effects on red blood cell(s) (RBCs), thereby
preserving the flexibility and deformability of RBCs. It has
been postulated that this might be due to the ability of
cinnarizine to block Ca2? entry in ischemic RBCs [7].
Another hypothesis adds that flunarizine, a cinnarizine
derivative, protects against Ca2? dependent ionophore
A23187-induced crenation of human RBCs, a condition
associated with decreased membrane deformability [10].
Action on Labyrinth
The action of cinnarizine on peripheral vestibular
structures has been demonstrated in various clinical
studies. During the early years of development (1976),
cinnarizine 25 mg at a thrice-daily (TID) dosage was noted
to be significantly superior to placebo in reducing the
amplitude, duration and speed of the slow phase of
post-rotational nystagmus and the total number of beats
(p \ 0.05) [11]. After 2 years, evidence confirmed that
cinnarizine significantly reduced the velocity of the slow
phase of caloric induced nystagmus in patients with
peripheral labyrinthine disorders [12]. Mechanism of
action of cinnarizine in the labyrinth involves inhibition of
Ca2? ion translocation across cell membranes of the
vestibular sensory cells in the ampullae. Overstall et al.
[13] however, have suggested that cinnarizine normalizes
endolymph flow by preventing constriction of the stria
vascularis. An additional mechanism of action of
cinnarizine in vestibular vertigo hypothesized that
cinnarizine modulates transmitter release in vestibular hair
cells (patch-clamp model). Haasler et al. [14] demonstrated
that inhibition of pressure-dependent K? currents in
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pharmacologically relevant concentrations of cinnarizine
(0.05–3 lM) elicited depolarization and increased
voltage-dependent activation of Ca2? currents, which
enhanced transmitter release.
Clinical Evidence
Vertigo accounts for *5% of total prevalence and an
incidence of 1.4% in adults. This high presentation rate is
probably due to the large number of underlying conditions
reported along with the symptom [15]. An Indian study
conducted in 2001 estimated the overall prevalence of
vertigo in rural adult community as 0.7% [16]. The
underlying cause might be either of the following reasons;
an involvement of labyrinth in the inner ear, or due to
dysfunction of the vestibular nerve, or the defect may
involve vestibular nuclei, or other centers responsible for
the maintenance of balance. For vertigo patients in the
latter two categories, the anti-vasoconstrictor properties of
cinnarizine might be beneficial in restoring blood flow by
improving the microcirculation in the affected region [17].
Peripheral Vertigo
This type of vertigo is due to problems originating in the
peripheral nervous system like benign paroxysmal
positional vertigo, acute vestibular neuronitis, or Ménière’s
disease. Some of the common triggers of peripheral vertigo
include alcohol and also drugs like anti-depressants,
antihypertensives, salicylates, hypnotics and sedatives.
Neurologic symptoms, hearing loss, severe nausea and
vomiting may be concomitant conditions presenting along
with peripheral vertigo [18]. Efficacy of cinnarizine in
various causes of peripheral vertigo has been established in
different clinical studies (Table 2).
Central Vertigo
Central vertigo may be caused by vascular insufficiency/
cerebral ischemia involving vestibular centers in brainstem,
cerebellum and disorders of the thalamus leading to
dizziness and unsteadiness. Cinnarizine has proven to be
effective in patients suffering from vertigo of central
origin. It improves the microcirculation in the affected
parts of brain like vestibular nuclei which results in
improved central vestibular function. In one of the earliest
studies in 1972, cinnarizine was shown to benefit patients
with central vertigo due to impaired cerebral circulation,
Indian J Otolaryngol Head Neck Surg (November 2019) 71(Suppl 2):S1060–S1068 S1063

Table 2 Cinnarizine in peripheral vertigo

Peripheral Study design Sample size Cinnarizine Comparator Result
causes dosage

Labyrinthitis Double-blind 14 45–90 mg/day Prochlorperazine 70%–80% improvement in severity of

crossover [33] for 4 weeks nausea and vomiting. 50%–60%
improvement in tinnitus. Efficacy
similar to prochlorperazine
MD Double-blind 20 45–90 mg/day Prochlorperazine 70%–80% improvement in symptom
crossover [33] for 4 weeks severity with cinnarizine and
prochlorperazine
MD Double-blind, 37 2 9 75 mg for Betahistine 3 9 16 mg for Betahistine resulted in higher
randomized study 8 weeks 8 weeks reduction of symptoms compared
[26] with cinnarizine
MD (with Open-label, 52 MD 20 mg BID/OD Combined therapy: betahistine Cinnarizine, proactively prevented
and non-randomized (n = 29 48 mg/day ? cinnarizine vertigo spells especially in MD
without [34] were 20 mg BID (1 month) and patients with migrane
migraine) migraineurs) then betahistine 20 mg/day
(for 2 weeks) and betahistine
20 mg every 2 days (for
2 more weeks) and then
successively restarted
Total duration: 6 months
Peripheral Double-blind, 221 adult 150 mg OD for Nimopidine 30 mg oral tablet Nimopidine and cinnarizine reduced
vertigo multinational pilot 12 weeks TID (one with breakfast, incidences of moderate vertigo
study [35] (with dinner) lunch and dinner) episodes by 78.8% and 65.8%
respectively and severe vertigo
incidences were decreased by
85.0% and 89.8%, respectively
Recurrent Randomized, 88 patients 2 9 15 mg TID Betahistine dihydrochloride Both drugs reported equal efficacy in
vertigo crossover study 2 9 12 mg TID reducing the duration and severity
[36] of symptoms at the end of
6 months
Seasickness Double-blind 335 15 mg TID for Placebo Vomiting prevented significantly by
placebo-controlled 5–7 days cinnarizine (75%, p \ 0.001) as
[37] whilst at compared with placebo (43%).
seasickness Drowsiness was reported by 8%
receiving cinnarizine and 5%
receiving placebo
Induced NR [38] 6 healthy 15 mg TID Betahistine 8 mg TID Nystagmus duration and average eye
vestibular volunteers speed were similar between
nystagmus pre-treatment rotation and
betahistine therapy (p [ 0.05).
Sudden stoppage of cinnarizine
therapy reported significant
differences in nystagmus duration
at initial acceleration as well as
average eye speed (p \ 0.05)
BID twice-daily, TID thrice-daily, MD Ménière’s disease, NR not reported, OD once-daily

irrespective of whether the symptom was a primary Pharmacokinetic Data

manifestation or a complication of some other disease
process [19]. Later, an in-vivo model demonstrated that
cinnarizine increases blood flow to the lateral vestibular
nucleus selectively in a non-dose dependent manner,
without affecting the reticulo-cortical, thalamo-cortical and
sensory trigeminal systems [20]. Table 3 shows important
clinical studies of cinnarizine in the management of vertigo
of central origin.
Pharmacokinetic data revealed that post-administration,
plasma levels of cinnarizine peak in 1–3 h. Total 91.0% of
cinnarizine is plasma-protein bound which is extensively
metabolized, largely by CYP2D6. The elimination half-life
for cinnarizine varied from 4 to 24 h; 33.0% of the
metabolites were eliminated by urine and 66.0% in the
feces [21]. Cinnarizine has a Cmax of 275 ± 36 ng/mL,

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S1064 Indian J Otolaryngol Head Neck Surg (November 2019) 71(Suppl 2):S1060–S1068
Table 3 Cinnarizine in central vertigo
Central causes Study design Sample size Cinnarizine dosage
Atherosclerosis Open-label [39] 82 25 mg TID 4 weeks NA
Cardiovascular Double-blind [40] 117 25 mg BID/TID
diseases
BID twice-daily, TID thrice-daily, NA not applicable
tmax 3.0 ± 0.5 h, AUC? 4437 ± 948 ng h/mL and
terminal half-life was 23.6 ± 3.2 h post 72 h of
administration [22].
Dosage Recommendations
Cinnarizine has been used in varying doses from 15 mg
TID to 150 mg/day in different clinical studies for vertigo
[Tables 2, 3]. In Europe, cinnarizine dosage as low as
15 mg is available. Cinnarizine is recommended as 25 mg
TID or 75 mg once-daily dosing for maintenance therapy
for symptoms of labyrinthine disorders, including vertigo,
dizziness, tinnitus, nystagmus, nausea and vomiting. The
maximum recommended dosage for cinnarizine is 225 mg
daily [21]. For motion sickness, the dosage for adults and
adolescents aged 13 years and above is 25 mg tablet: one
tablets at least half an hour before travelling and one tablet
every 6 h during the journey [21].
Role of Cinnarizine in Combination
with Dimenhydrinate in Vertigo
The fixed dose combination of cinnarizine ? dimenhydrinate,
with its dual mechanism of action, allows the simultaneous
functional regulation of the peripheral and central
vestibular components [23]. Cinnarizine acts
predominantly peripherally on the labyrinth, causing
increased cerebral and cochlear perfusion as well as
vestibular suppression through inhibition of Ca2? channels
in vestibular sensory cells; thus improving inner ear
circulation. Dimenhydrinate acts centrally on the vestibular
nuclei and associated centers in the brainstem; and
additionally acts as an anti-histamine, anti-cholinergic,
anti-emetic and anti-vertiginous activity alleviating acute
vertigo attacks. Due to these combined pharmacological
properties of cinnarizine ? dimenhydrinate, the fixed dose
combination is favorable in the management of various
vestibular disorders [24] (Fig. 2).
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Comparator Result
Significant improvement (p \ 0.001) in dizziness,
unsteady gait, tinnitus, concentration loss,
memory loss, inactivity, listlessness, headache
and troubled sleep
Vincamine Cinnarizine was superior to vincamine against
dizziness and tinnitus
Many randomized, double-blind clinical studies have
clearly demonstrated the efficacy and tolerability of the
fixed dose combination of cinnarizine ? dimenhydrinate in
comparison with standard monotherapies in various defined
pathological entities, including otogenic vertigo, vestibular
neuropathy, vertigo in vertebrobasilar insufficiency and
Ménière’s disease (Table 4).
Renal and Hepatic Insufficiency
No specific studies have been reported on the use of
cinnarizine in patients with hepatic or renal dysfunction.
However, it is recommended that cinnarizine be used with
care in patients with such conditions [25].
Pregnancy and Lactation
No teratogenic effects with use of cinnarizine have been
reported in pre-clinical studies [21]. The safety of
cinnarizine in pregnant or lactating women has not been
established in clinical studies. Cinnarizine should be used
during pregnancy only if the therapeutic benefits justify the
potential risks for the fetus/infant as indicated by a
physician. As there is no data available on secretion of
cinnarizine in breast milk, nursing should be discouraged in
women using cinnarizine [21].
Safety Profile
Cinnarizine and its combinations have shown no safety
concerns and are well-tolerated. An analysis of seven
placebo-controlled, double-blind clinical studies of
cinnarizine (30–225 mg/day) was conducted to evaluate
safety in total 740 patients (cinnarizine: 372 patients and
placebo: 368 patients). Drowsiness/somnolence was
encountered in some patients (\10%), especially at the
start of treatment. Therefore, caution should be exercised
Indian J Otolaryngol Head Neck Surg (November 2019) 71(Suppl 2):S1060–S1068
Fig. 2 Mechanism of action of fixed dose combination of cinnarizine and dimenhydrinate
when concomitant drugs having central nervous system
depressant action are taken and activities like driving and
operating machinery should be avoided [21]. Nausea and
weight gain were other adverse events reported during
some of the clinical studies [21, 26].
Incidences of extrapyramidal symptoms and drug-induced
Parkinsonism were very rare during the post-marketing
surveillance studies. The results on recurrent labyrinthine
disturbances have demonstrated that cinnarizine administered
for the long-term control of labyrinthine disorders does not
have serious side effects [27]. However, patients with
Parkinson’s disease should be prescribed cinnarizine only if
the advantages outweigh the possible risk of aggravating the
disease.
The combination of cinnarizine ? dimenhydrinate was
evaluated for adverse events. An analysis of data from five
randomized, double-blind clinical studies concluded that
combination of cinnarizine ? dimenhydrinate was
well-tolerated and with 90.3% of the patients reported the
tolerability as ‘very good’ or ‘good’. Most common side
effects reported were fatigue or somnolence, closely
followed by dry mouth. Other adverse events reported were
headache, abdominal pain, nausea and tremors [27, 28]. In
a German, prospective, non-interventional study carried
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out in primary and secondary care private practices,
combination of cinnarizine ? dimenhydrinate therapy was
evaluated in the treatment of vertigo of various origins. In
addition to reduction in mean vertigo score in the 1275
patients, nausea, vomiting and tinnitus were also reduced
by 84%, 85% and 51%, respectively, and non-serious
adverse events were reported in 4.2% of the population
[29]. Overall, combination of cinnarizine ? dimenhydrinate
demonstrated a better benefit-risk ratio than either individual
monotherapy [30].
Limitations
Consensus rating of the article quality was not performed
because it was beyond the scope of the current review. The
reliability of the article selection and classification was not
assessed because only one reviewer was involved in the
process albeit the potential source of bias is minimal since
only basic descriptive information was extracted from each
article. As the studies selected for this review spanned a
course of four decades, it is very likely that the endpoints,
conduct of study and analysis variability could have been
overlooked.
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Table 4 Cinnarizine in combination with dimenhydrinate: clinical evidence

Causes of vertigo Study design Sample Comparator Result
size

Ménière’s disease Double-blind, randomized
control [41]
Otogenic vertigo Prospective, double-blind,
randomized, comparative,
single-center study [42]
Vertebrobasilar Double-blind, randomized
insufficiency control [43]
Vertebrobasilar NR [44]
insufficiency
Vestibular disorders Double-blind, randomized
control [24]
Vestibular neuritis Double-blind, randomized
control [31]
Vertigo of peripheral Randomized, double-blind,
or central, combined active- and
peripheral/central placebo-controlled,
origin parallel-group, outpatient
study [45]
Vertigo of various Prospective, double-blind,
origins randomized active-controlled,
multicenter study [23]
Acute unilateral Prospective, single-center,
vestibular loss randomized, double-blind,
parallel-group [29]
Vertigo and tinnitus of Double-blind, randomized
peripheral or central control [46]
origin
a
Betahistine dimesylate was used as an active comparator of cinnarizine ? dimenhydrinate clinical study. BID twice-daily, TID thrice-daily, NR
not reported
82 Betahistinea 12 mg Both drugs led to a marked reduction of vertigo
TID for 12 weeks symptom score. Similar efficacy and safety
were reported between the combination and
betahistine
61 Betahistine 12 mg TID Fixed dose combination decreased the intensity
for 4 weeks of vertigo symptoms about twofold than
betahistine (p = 0.001) at 4 weeks and this
was more evident post 4 weeks of treatment
(p = 0.009)
37 Betahistinea 12 mg Fixed dose combination showed significantly
TID for 4 weeks or greater reductions of vertigo symptom score as
placebo compared to patients receiving betahistine
(p \ 0.01)
78 Cinnarizine and Dual action of the combination therapy revealed
dimenhydrinate BID symptom reduction of tinnitus (38.7%) and
for 60 consecutive dizziness (43.1%). Reduction was also
days observed in the tinnitus handicap inventory
and dizziness handicap inventory score at final
examination (p \ 0.001)
66 Betahistine 12 mg TID The cinnarizine ? dimenhydrinate fixed dose
for 4 weeks combination therapy reported significantly
greater improvements in mean vertigo scores
than betahistine (p = 0.013)
62 Betahistine 12 mg each The fixed dose combination therapy reported
TID for 4 weeks significantly greater improvements in mean
vertigo score than betahistine (p \ 0.001).
Activities of daily living also improved
significantly with the combination than
betahistine (p \ 0.01)
246 Placebo, TID for In those patients with mean vertigo score B0.5
4 weeks after 4 weeks of treatment, the fixed dose
combination was effective in 62.3% of patients
than 29.5% in cinnarizine 50 mg, 30.5% in
dimenhydrinate 100 mg and 24.1% in placebo
group
182 Cinnarizine 20 mg or Reduction in mean vertigo score post four weeks
dimenhydrinate of treatment with the fixed dose combination
40 mg, each TID for was significantly greater than each of the
4 weeks monotherapy alone (p = 0.0001)
50 Cinnarizine 20 mg or Fixed dose combination was significantly more
dimenhydrinate effective than either of the monotherapy
40 mg, TID for (cinnarizine, p \ 0.001 and dimenhydrinate,
4 weeks p \ 0.01)
122 Cinnarizine 20 mg or Fixed dose combination was more effective than
dimenhydrinate either of its constituent drugs used as
40 mg, TID for monotherapy
4 weeks

Expert Opinion theories have been postulated on interaction of various

Pharmacotherapy plays an important role in control of
vertiginous symptoms in patients with vestibular disorders.
Therapy duration should be decided by the treating
physician based on the etiology of symptoms. Multiple
drugs with vestibular compensation though the supporting
evidence is lacking, but duration of therapy is known to
play an important role in timely management of vestibular
disorders. It has been demonstrated that the combination of
cinnarizine ? dimenhydrinate causes partial recovery of

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Indian J Otolaryngol Head Neck Surg (November 2019) 71(Suppl 2):S1060–S1068
the caloric nystagmus at the affected site, resulting in
gradual decrease in spontaneous nystagmus with minimal
effect on vigilance which does not affect the vestibular
invoked myogenic potential outcomes. This might suggest
that the central compensation processes is not suppressed
by the combination therapy [30, 31].
Conclusion
Cinnarizine has gained significant importance and has been
established as a first-line pharmacotherapy in vertigo
management basis clinical evidences generated over the
last four decades. Recent literature has proven that the
fixed dose combination of cinnarizine ? dimenhydrinate is
an effective therapeutic option in treating vertigo due to
various causes. Treatment with cinnarizine ? dimenhydrinate
combination was efficacious and demonstrated good
tolerability among the majority of patients. Thus, this
combination therapy in vertigo of various origins seems
viable and beneficial alternative in the treatment of vertigo.
In conclusion, cinnarizine and its combinations can make
an important contribution to healthcare by optimal
treatment of patient presenting with vertigo, one of the
most common presenting symptom across all specialties of
medicine.
Key Messages
• Cinnarizine, established as a first-line pharmacotherapy
in vertigo management is efficacious due to its
peripheral and central action.
• A thorough literature survey emphasized clinical
efficacy and safety of cinnarizine versus placebo and
other comparators.
• Combination therapy of cinnarizine and dimenhydrinate
is likely a viable and beneficial alternative in vertigo
treatment.
Acknowledgements Dr. Sonia Philipose (SIRO Clinpharm Pvt. Ltd.)
provided editorial support for this manuscript. This work was
supported by funding from Janssen India.
Compliance with Ethical Standards
Conflict of interest None.
Disclosure Dr. Ravi Santani and Dr. Prashant Narang are employees
and/or shareholders of Janssen, India. All authors contributed to the
data interpretation and development of the review. All authors met
ICMJE criteria and all those who fulfilled those criteria are listed as
authors. All authors had access to the study data, provided direction
and comments on the manuscript, made the final decision about where
to publish these data and approved submission to the journal.
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References
1. Emanuel MB, Will JA (1977) Cinnarizine in the treatment of
peripheral vascular disease: mechanisms related to its clinical
action. Proc R Soc Med 70:7–12
2. Soto E, Vega R (2010) Neuropharmacology of vestibular system
disorders. Curr Neuropharmacol 8:26–40
3. National formulary of India, fourth edition, 2011. http://www.
cdsco.nic.in/writereaddata/NFI_2011%20(1).pdf. Accessed 17 Oct
2016
4. Drugs Controller General of India. List of approved drug from
01.01.2010 to 31.12.2010. http://www.cdsco.nic.in/writereaddata/
list-of-approved-drug-from-01-01-2010-TO-31-12-2010.pdf.
Accessed 17 Oct 2016
5. Oosterveld WJ (1999) Cinnarizine in the vertiginous syndrome.
In: Towse G (ed) cinnarizine and the vertiginous syndrome.
International Congress and Symposium Series No. 33. Royal
Society of Medicine and Academic Press Inc, London, pp 29–37
6. Möttönen T, Hannonen P, Leirisalo-Repo M, Nissilä M,
Kautiainen H, Korpela M et al (1999) Comparison of
combination therapy with single-drug therapy in early rheumatoid
arthritis: a randomized trial. FIN-RACo trial group. Lancet
353:1568–1573
7. Di Perri T, Forconi S, Guerrini M, Pasini FL, Del Cipolla R,
Rossi C et al (1977) Action of cinnarizine on the hyperviscosity
of blood in patients with peripheral obliterative arterial disease.
Proc R Soc Med 70:25–28
8. Van Nueten JM, Janssens WJ (1988) Cerebral antivasoconstrictive
effects of flunarizine. Acta Otolaryngol 105:42–49
9. Dormandy JA, Hoare E, Khattab AH, Arrowsmith DE, Dormandy
TL (1973) Prognostic significance of rheological and biochemical
findings in patients with intermittent claudication. Br Med J
4:581–583
10. De Clerck F, Beerens M, Thoné F, Borgers M (1981) Effect of
flunarizine on the human red cell shape changes and calcium
deposition induced by A 23187. Thromb Res 24:1–12
11. Cobb S, Coen LW, Gitomer SL, Iles R (1976) Effect of cinnar-
izine on nystagmus induced by rotation-deceleration. Eye Ear
Nose Throat Mon 55:48–30
12. Mangabeira-Albernaz PL, Ganança MM, Novo NF, de Paiva ER
(1978) Flunarizine and cinnarizine as vestibular depressants. A
statistical study. ORL J Otorhinolaryngol Relat Spec 40:92–100
13. Overstall PW, Hazell JW, Johnson AL (1981) Vertigo in the
elderly. Age Ageing 10:105–109
14. Haasler T, Homann G, Duong Dinh TAD, Jüngling E, Westhofen
M, Lückhoff A (2009) Pharmacological modulation of transmitter
release by inhibition of pressure-dependent potassium currents in
vestibular hair cells. Naunyn Schmiedebergs Arch Pharmacol
380:531–538
15. Neuhauser HK, Lempert T (2009) Vertigo: epidemiologic
aspects. Semin Neurol 29:473–481
16. Abrol R, Nehru VI, Venkatramana Y (2001) Prevalence and
etiology of vertigo in adult rural population. Indian J Otolaryngol
Head Neck Surg 53:32–36
17. Godfraind T, Towse G, Van Nueten J (1982) Cinnarizine: a
selective calcium entry blocker. Drugs Today 18:27–42
18. Labuguen RH (2006) Initial evaluation of vertigo. Am Fam
Physician 73:244–251
19. Toledo JB, Pisa H, Marchese M (1972) Clinical evaluation of
cinnarizine in patients with cerebral circulatory deficiency.
Arzneimittelforschung 22:448–451
20. Fujimoto S, Sasa M, Takaori S, Matsuoka I (1978) Selective
effect of cinnarizine on the vestibular nucleus neurons. Arch
Otorhinolaryngol 221:37–45
123
S1068 Indian J Otolaryngol Head Neck Surg (November 2019) 71(Suppl 2):S1060–S1068
21. Stugeron (cinnarizine). http://www.janssen.com/southafrica/
sites/www_janssen_com_southafrica/files/product/pdf/
stugeron_pi_mar_2013_eng_port_0.pdf. Accessed 24 Sept 2016
22. Castañeda-Hernández G, Vargas-Alvarado Y, Aguirre F,
Flores-Murrieta FJ (1993) Pharmacokinetics of cinnarizine after
single and multiple dosing in healthy volunteers.
Arzneimittelforschung 43:539–542
23. Hahn A, Novotný M, Shotekov PM, Cirek Z, Bognar-Steinberg I,
Baumann W (2011) Comparison of cinnarizine/dimenhydrinate
fixed combination with the respective monotherapies for vertigo
of various origins: a randomized, double-blind, active-controlled,
multicentre study. Clin Drug Investig 31:371–383
24. Hahn A, Sejna I, Stefflova B, Schwarz M, Baumann W (2008) A
fixed combination of cinnarizine/dimenhydrinate for the
treatment of patients with acute vertigo due to vestibular
disorders: a randomized, reference-controlled clinical study. Clin
Drug Investig 28:89–99
25. STUGERON. www.meppo.com/pdf/drugs/2444-stugeron-13297
53152.pdf. Accessed 24 Sept 2016
26. Djelilovic-Vranic J, Alajbegovic A, Tiric-Campara M, Volic A,
Sarajlic Z, Osmanagic E et al (2012) Betahistine or cinnarizine
for treatment of Meniere’s disease. Med Arch 66:396–398
27. Towse G (1980) Cinnarizine-a labyrinthine sedative. J Laryngol
Otol 94:1009–1015
28. Schremmer D, Bognar-Steinberg I, Baumann W, Pytel J (1999)
Efficacy and tolerability of a fixed combination of cinnarizine and
dimenhydrinate in treatment of vertigo: analysis of data from five
randomised, double-blind clinical studies. Clin Drug Invest
18:355–368
29. Scholtz A-W, Ilgner J, Loader B, Pritschow BW, Weisshaar G
(2016) Cinnarizine and dimenhydrinate in the treatment of
vertigo in medical practice. Wien Klin Wochenschr 128:341–347
30. Scholtz AW, Schwarz M, Baumann W, Kleinfeldt D, Scholtz H-J
(2004) Treatment of vertigo due to acute unilateral vestibular loss
with a fixed combination of cinnarizine and dimenhydrinate: a
double-blind, randomized, parallel-group clinical study. Clin
Ther 26:866–877
31. Scholtz A-W, Steindl R, Burchardi N, Bognar-Steinberg I,
Baumann W (2012) Comparison of the therapeutic efficacy of a
fixed low-dose combination of cinnarizine and dimenhydrinate
with betahistine in vestibular neuritis: a randomized,
double-blind, non-inferiority study. Clin Drug Investig
32:387–399
32. Trkanjec Z, Aleksić-Shibabi A, Demarin V (2007)
Pharmacotherapy of vertigo. Rad za Medicinske Znanosti 69–76
33. Whaetley D (1973) Reports from the general practitioner research
group; anthistamines and phenothiazine compared in vertigo.
Practitioner 211:224–227
34. Teggi R, Gatti O, Sykopetrites V, Quaglieri S, Benazzo M, Bussi
M (2014) Association of cinnarizine and betahistine in
123
prophylactic therapy for Ménière’s disease with and without
migraine. Acta Otorhinolaryngol Ital 34:349–353
35. Pianese CP, Hidalgo LOV, González RH, Madrid CE, Ponce JE,
Ramı́rez AM et al (2002) New approaches to the management of
peripheral vertigo: efficacy and safety of two calcium antagonists
in a 12-week, multinational, double-blind study. Otol Neurotol
23:357–363
36. Deering RB, Prescott P, Simmons RL, Downey LJ (1986) A
double-blind crossover study comparing betahistine and
cinnarizine in the treatment of recurrent vertigo in patients in
general practice. Curr Med Res Opin 10:209–214
37. Hargreaves J (1980) A double-blind placebo controlled study of
cinnarizine in the prophylaxis of seasickness. Practitioner
224:547–550
38. Cullen JR, Hall SJ, Allen RH (1989) Effect of betahistine
dihydrochloride compared with cinnarizine on induced vestibular
nystagmus. Clin Otolaryngol Allied Sci 14:485–487
39. Amery WK, Oosterveld WJ (1975) An evaluation of cinnarizine
in aged patients with vertiginous complaints-a multicentre trial.
Acta Ther 1:39–43
40. Udvarhelyi A (1978) Comparative study of the effect of devincan
and stugeron in patients suffering from cerebrovascular diseases
treated at medical departments. Ther Hung (English edition)
26:29–32
41. Novotný M, Kostrica R (2002) Fixed combination of cinnarizine
and dimenhydrinate versus betahistine dimesylate in the
treatment of Meniere’s disease: a randomized, double-blind,
parallel group clinical study. Int Tinnitus J 8:115–123
42. Cirek Z, Schwarz M, Baumann W, Novotny M (2005) Efficacy
and tolerability of a fixed combination of cinnarizine and
dimenhydrinate versus betahistine in the treatment of otogenic
vertigo: a double-blind, randomised clinical study. Clin Drug
Investig 25:377–389
43. Otto V, Fischer B, Schwarz M, Baumann W, Preibisch-Effenberger
R (2008) Treatment of vertebrobasilar insufficiency-associated
vertigo with a fixed combination of cinnarizine and dimenhydrinate.
Int Tinnitus J 14:57–67
44. Martines F, Agrifoglio M, Bentivegna D, Mucia M, Salvago P,
Sireci F et al (2012) Treatment of tinnitus and dizziness
associated vertebrobasilar insufficiency with a fixed combination
of cinnarizine and dimenhydrinate. Acta Med Mediterr
28:291–296
45. Pytel J, Nagy G, Tóth A, Spellenberg S, Schwarz M, Répassy G
(2007) Efficacy and tolerability of a fixed low-dose combination
of cinnarizine and dimenhydrinate in the treatment of vertigo: a
4-week, randomized, double-blind, active-and placebo-controlled,
parallel-group, outpatient study. Clin Ther 29:84–98
46. Novotny M, Kostrica R, Cirek Z (1999) The efficacy of arlevert
therapy for vertigo and tinnitus. Int Tinnitus J 5:60–62