164 Australian Dental Journal, April, 1978

Volume 23,
No. 2

A clinical evaluation of benzydamine hydrochloride

K. MacD. Hunter, M.D.S.

Department of Oral Surgery, University of Otago Deli fa1 Scliool

ABSI-RACT-A double-blind clinical trial of the effects of the use of benzydamine hydrochloride
for patients undergoing the surgical removal of impacted lower third molar teeth showed n o
significant effects on swelling and trismus between control and experimental groups, although
a significant reduction in the post-operative consumption of analgesics was noted.

(Rrcc~ivcdfor prrhlicatiori March, 1977)

Introduction stimulus or agent on otherwise normal tissues. Less

Benzydamine hydrochloride* is an anti-inflam-
matory drug unrelated t o other anti-inflammatory
agents such as corticosteroids, salicylates, phenyl-
butazone, and indomethacin. I t was first synthesized
in 1960 and is available in many countris under
the trade names Bemzylin, Imotryl and Riripen.
Appraisals of the effectiveness of benzydamine
hydrochloride as a n anti-inflammatory agentl. 2. 7
have suggested that this drug is most active in
decreasing primary inflammation, that is inflam-
mation resulting from the action of a noxious
* Tantum, Fawns and McAllan, Australia.
1 de Gregorio, M.-Guidelines in the clinical testing of
anti-inflammatory drugs. Excerpta Medica International
Congress Series, No. 163, Bologna, November, 1961.
2 de Gregorio M -Some clinical data o n benzydamine.
Excerpta kedjca International Congress Series, No. 82,
Milan,, September, 1964.
Silvestrini, B., Garau. A.. and Pozzatti, C.-Pharmacw
logical research on Benzydamine - a new analgesic-
anti-inflammatory drug. Arzneimittel-Forschung, 16: I ,
59-63 (Jan.) 1966.
effect is seen when inflammation is a result of ab-
normal tissue reactivity, as in chronic rheumatic
conditions.
The double-blind clinical trial described below
was designed t o test the suggestion that benzyda-
mine hydrochloride may ease post-operative dis-
comfort arising from oedema and trismus follow-
ing the removal of impacted lower third molar
teeth.
Method
Fifty patients were selected for the trial, selec-
tion being based on the patients need for the
removal of an impacted lower third molar, and on
the absence of any local or medical history that
may have influenced the action of the trial drug.
Suitable patients were aged 18-25 years and an
equitable ratio of men and women with left and
right operative sides was also ensured.
Two days before the surgery, patients collected
a coded supply of benzydamine hydrochloride
tablets; o r identical glucose placebo!:, the identity
Australian Dental Journal, April, 1978 165

of the tablets being held in a code which was not Results

broken until the completion of the clinical part of At the completion of the clinical stage of the
the trial. The patient was instructed t o take one trial, the drug distribution coding was broken
tablet four times daily from the day preceding and patient records divided into active drug or
operation until the sixth post-operative day. Benzy- placebo groups for statistical analysis.
damine hydrochloride was thus administered in
50 mg doses four times daily for seven days.
Before the main body of the trial was under-
taken, a small pilot study and repeated measure- TABLE1
ment test yielded a reliable reproducible method Distribution of drug trial patients
for the objective measurement of swelling and Placebo Benzydamine HCI Total
trismus. The latter was gauged by a comparison of
midline incisal edge separation upon unforced Women 8 11 19
Men 15 10 25
opening, the mean of three consecutive measure- Total 23 21 44
ments was recorded. Similarly, a comparison of
pre-operative and post-operative measurements of
cheek thickness was used t o judge swelling. The
instrument used to obtain buccal thickness TABLE
2
measurements was an engineers caliper, modified Difference in measurements for tri.wiu.\ and
by brazing a 1.5 cm x 1 cm plate to the end of swelling between control and experimental
each caliper to avoid pinching the cheek. With groups
one arm extra-orally and with intermaxillary
Trismus (loss in mm) Swelling (gain in mm)
separation just sufficient to allow caliper intro- Grour, 24hrs 3davs 6davs 24 hrs 3 davs 6davs
duction, readings of buccal thickness were taken Benzydamine
alongside the buccal aspect of the lower second HCI 9.9 6.1 2.7 3.3 2.4 1.0
molar. Measurement of buccal thickness and in- Placebo 13.9 10.7 6.5 3.5 2.2 0.6
cisal edge separation was performed immediately, Difference -4.0 -4.6 -3.8 -0.2 +0.2 $0.4
pre-operatively and 24 hours, three days and six
days post-operatively, with a timing latitude of plus
or minus one hour. TABLE
3
All surgery and measurement was carried out Mean daily post-operative analgesic consumption
by the one operator. At the time of surgery, only
the one lower third molar was removed, and the Mean number of analgesic tablets
per patient
degree of difficulty of each case assessed by the Benzydamine HCI
Post-operative day Placebo group group
time taken t o complete the procedure. This
arbitrary difficulty grading ranged from five Day 1 3.5 1 2.25
minutes or less (Grade I) by five minute incre- Days 2 and 3 0.95 0.75
Days 4, 5 and 6 0.35 0.01
ments to 20 minutes or more (Grade V). A
butobarbitone-codeine-paracetamol compound* * *
was used as a pre-operative sedative, and all
surgery was performed under regional analgesia.
Of the 25 patients in each of the two groups a
At the three post-operative checks, subjective total of six were deleted from the results; five of
assessments were made in addition t o objective these for failure t o return for post-operative
measurements. This involved the clinical assess- checks, and one whose drug regime was halted
ment of swelling and pain, on a four-point scale. in view of reported severe gastric upset, insomnia,
An attempt to measure objectively post-operative and cutaneous rash. The distribution of the remain-
pain was also made by monitoring the number of ing 44 patients is illustrated in Table 1.
analgesic compound tabletsf consumed between
check intervals. These tablets were supplied to the
A number of variables that may have influenced
results required statistical investigation before
patient immediately post-operatively with instruc-
analysis of the main body of the results could be
tions to record the number consumed.
considered. These variables included differences in
mean difficulty grading between placebo and active
drug groups, and differences between the two
groups in 1eft:right operative side and male:
* Tantum, Fawns and McAllan, Australia. female ratios. The analysis showed that these
** Supplied by Fawns and McAllan, Australia. factors could not be regarded as having any
*** Dolalgin May and Baker New Zealand. significant effect on the results obtained.
$. Codis, ReGkitt and Colema;. New Zealand.
 166
Student's ?'-tests were performed on the raw
data provided by measurements at each post-
operative check. The results of this analysis show
n o difference in control of swelling and only
slightly significant difference in trismus.
The subjective assessment of post-operative swel-
ling did not detect any difference between the two
groups, but a difference in the consumption of
analgesic tablets was noted. Table 3 shows the
distribution of analgesic consumption.
There is a statistically significant difference in
analgesic consumption in the period to 24 hours
post-operatively ( P < 0.01).
Discussion
Trismus and pain suffered by a patient who has
undergone minor oral surgery for the removal of
lower third molars can be considerable and
frequently accentuated by unsightly swelling.
Shaw4 reported a reduction in post-operative pain,
oedema and inflammation with minimal side effects
when a dose of 100 mg of benzydamine hydro-
chloride was administered orally four time daily,
while Daigle and Chesnay5 concluded that local
topical application in the form of a mouth rinse
was more effective than systemic administration.
Table 2 shows minimal mean difference in buccal
swelling between the group given the placebo and
that administered benzydamine hydrochloride. The
difference in trismus is greater between the two
groups. The difference in trismus, although more
ohviously favouring the group receiving benzyda-
mine hydrochloride. is only at the margins of
%tatistical significance. Menzels, reporting a signi-
ficant reduction in post-operative oedema, set a
confidence level of 90 per cent ( P < 0.10), arguing
that the unreliability of drug intake by patients
could favourably influence results. Since benzyda-
mine hydrochloride use for post-operative relief
following minor oral surgery is most likely to be
used in an outpatient situation, this problem could
he encountered during the routine use of the drug.
For this reason, P < 0.05 was retained in this
current study as the confidence level required. We
must therefore conclude that the reduction in
trismus observed in this study cannot be statisti-
cally substantiated at this more stringent level of
confidence.
The difference in post-operative analgesic con-
- Dental School,
' Shaw, W. F.-Un ublished, undated data.
Daigle L. and d e s n a y G.-Un ublished undated data.
"Menzei H' J.-untersuchun en uger die Odempro hYldXe
mit 'Benzydamin (Tanturn5 nach zahnartzlich cgiruigi-
schen Eingriffen. Zahnarztliche Welt Reform, 8 0 : 12,
57&3 (June) 1971.
7 Heudy, J.-Unpublished data, 1970.
Australian Dental Journal, April, 1978
sumption (Table 3 ) is statistically significant in
the period to 24 hours post-operatively ( P < 0.01 ).
Although Reudy7 found no difference in pain
control between benzydamine hydrochloride and
a codeine compound, the former is undoubtedly
of benefit in providing post-operative analgesia
during the first 24 hours, the period when pain
control is most necessary. A reduction of the mean
difference in swelling and trismus between the two
groups may have been caused by the significantly
greater consumption of aspirin-containing analgesic
compound by the placebo group. This would have
had the effect of reducing the statistical significance
of the effect of benzydamine hydrochloride.
If the patient gives a history of gastric secretory
disturbance the use of benzydamine hydrochloride
is contraindicated: furthermore, as with all new
drugs, it is not recommended for use during
pregnancy. The side effects noted in this trial were
few and minor and involved only five patients.
Three of these patients complained of insomnia,
two of gastric upset, and one reported visual dis-
turbance. These effects have all been noted in
previous studies4 5 - 6 7 . When the patient was
instructed to take the drug with a meal, rapid
disappearance of untoward effects followed.
The most severely affected patient, for whom
drug administration was discontinued, complained
of insomnia, severe vomiting and the appearance
of a cutaneous rash. It was later revealed, upon
breaking the drug codes, that this patient had
been receiving placebo.
Summary
A double-blind clinical trial was performed to
measure the efficacy of benzydamine hydrochloride
in reducing post-operative swelling, trismus and
pain. With the dosage and route of administration
used (50 mg orally four times daily for seven days
covering the operative and post-operative period),
the observed differences in swelling and trismus
between active drug and placebo groups could not
be substantiated statistically. The differences may
have been masked by a higher post-operative rate
of consumption of aspirin-containing analgesic by
the placebo group. The active drug group consumed
a significantly smaller amount of post-operative
analgesic than the control group. from which it
was concluded that benzydamine hydrochloride
decreased the severity of post-operative pain.
Department of Oral Surgery.
University of Otago.
P.O. Box 647.
Dunedin,
New Zealand.