SERC (Betahistine hydrochloride)

TABLETS DESCRIPTION AND CHEMISTRY:

SERC is the proprietary name for a histamine-like drug generically designated as betahistine
hydrochloride. The chemical name is 2 (2' meihylaminoethyl) pyridine dihydrochloride. There is
some similarity in structure between betahistine and histamine.

ACTION:

Betahistine was found to have a histamine-like action in animals. Since parenteral histamine has
been used in the treatment of Meniere's disease, studies were conducted to test the action of
betahistine in this condition. Unlike some other anti-vertigo drugs, testing with nystagmus
induced by caloric and rotational stimulation has demonstrated that betahistine does not decrease
the vestibular response, as recorded by electronystagmography. In addition, the absorption,
metabolism and action of betahistine when administered by the oral route are not known.
However, clinical studies indicate that SERC may be useful in reducing the vertigo of Meniere's
disease.

INDICATIONS:

SERC may be of value in reducing the episodes of vertigo in Meniere's disease.

CLINICAL USE:

The extremely variable course of Meniere's disease makes it almost impossible to predict.
Consequently, assessment of the results of treatment is fraught with difficulties since
spontaneous remissions or a placebo effect cannot be excluded, short of conducting prolonged
studies extending over a period of years. The implication is that some information must be
accepted from controlled trials falling short of an entirely acceptable design. In addition , most
trials with betahistine have included a choice of patients with frequent episodes of vertigo that
may not be representative of a cross section of patients with Meniere's disease.

No studies are available comparing betahistine with other antivertigo agents. SERC has not been
demonstrated to have any effect on the evolution or progression of Meniere's disease and it
appears not to eliminate the development of incapacitating vertigo and the subsequent need for
surgery in some patients.

No claim is made for the effectiveness of SERC in the symptomatic treatment of any form of
vertigo other than that associated with Meniere's disease. It also has not been established that
betahistine has any effect on other manifestations of Meniere's disease.

Meniere's disease, or idiopathic labyrinthine hydrops, is characterized clinically by recurrent

episodes of vertigo accompanied by, usually unilateral, tinnitus and hearing loss. Nausea and
vomiting may also occur. The vertigo lasts from a few minutes to several hours. Other forms of
aural vertigo may be distinguished only because they tend to last longer. As a rule, between
dizzy spells there are no other complaints save for varying levels of hearing and tinnitus. The
prognosis in individual patients with Meniere's is difficult to predict. Some patients have mild or
major dizzy spells in frequent clusters, possibly once or twice weekly, for a period of several
weeks or months, then have remission of episodes which may last for months or years. Others
may have vertiginous attacks only once or twice yearly. Virtually none have daily spells, and
continuous vertigo in the sense of dizziness without remission for many days or weeks. In
general, hearing is poorer and tinnitus loud when vertiginous attacks are frequent. Hearing may
return to normal between attacks in early cases, but as time progresses, hearing slowly
deteriorates, whether dizzy spells occur or not. In general, early Meniere's is featured by hearing
levels which become worse with vertiginous attacks and improve even to normal between the
attacks, while in late Meniere's hearing loss is less directly related to dizziness. The pathology of
Meniere's disease consists of distention of the membranous labyrinth associated with
accumulation due to overproduction or under absorption of endolymph.

CONTRAINDICATIONS:

Several patients with a history of peptic ulcer have experienced an exacerbation of symptoms
while using SERC. Although no causal relation has been established SERC is contraindicated in
the presence of peptic ulcer and in patients with a history of this condition. SERC is also
contraindicated in patients with pheochromocytoma.

PRECAUTIONS:

Although clinical intolerance to SERC by patients with bronchial asthma has not been
demonstrated, caution should be exercised if the drug is used in these patients.

SERC should not be used concurrently with antihistamine agents since no information is
available with regard to the possible interaction of these drugs.

The physician should be aware of the possibility of hitherto unreported adverse reactions to
SERC.

USE IN PREGNANCY:

The safety of SERC in pregnancy has not been established. Therefore, its use in pregnancy or
lactation, or in women of child bearing age requires that its potential benefits be weighed against
the possible risks.

ADVERSE REACTIONS:

Occasionaly patients have experienced gastric upset, nausea and headache.

PHARMACOLOGY:

In the course of animal studies, the response to betahistine, following intravenous administration,
and its action on a variety of isolated and intact tissues, resembled some of the responses to
histamine. Intravenous administration of SERC produced a transient increase in blood flow
through the labyrinthine artery in dogs, preceded by a fall in pulse pressure reflecting a systemic
response. It is assumed that SERC could act by decreasing endolymphatic pressure as a result of
increased vascularization. However, there is no experimental evidence of an increased perfusion
of the stria vascularis or evidence that changes occur in the fluid physiology of the inner ear that
would decrease distension of the membranous labyrinth. In addition, information on absorption,
metabolism and excretion of betahistine hydrochloride has not yet been obtained.

TOXICOLOGY:

The lethal dose of betahistine hydrochloride for the albino rat is 3040 mg./kg. by the oral route.
By the intravenous route the lethal dose for the rabbit is 5.1 mg./kg. The main signs of toxicity
observed were: ataxia, salivation, inactivity, hyperpnea, tremors and cyanosis. The pathology
revealed severe gastroenteritis.

A two-litter reproductive study with rats revealed no adverse effects.

Chronic toxicity studies in dogs given doses up to 25 mg./kg./day for eighteen months, revealed
no significant abnormalities in the parameters measured.

CLINICAL STUDIES:

In the course of clinical trials with SERC several hundred patients with Meniere's disease were
treated with this product. These studies have ranged from clinical experience with this drug
during short or long periods of treatment to double-blind, placebo controlled trials. In view of the
unpredictable natural history of Meniere's disease, no judgment of efficacy is possible in many
studies with faulty designs or other serious defects.

One study included approximately 60 patients with Meniere's disease, followed in a longitudinal
fashion without a concurrent control group. All patients had evaluation of the vestibular function
recorded by electronystagmography. The results of this study favor the efficacy of SERC in
reducing vertigo. In addition, the vestibular function improved in the majority of patients that
had a subjective response to the drug.

Three double-blind placebo controlled studies suggest a possible therapeutic effect of the drug.
No untoward clinical effects were noted.

DOSAGE AND ADMINISTRATION:

The usual adult dosage has been one to two tablets (4mg. each) administered orally three times a
day. The dosage has ranged from two tablets per day to eight tablets per day. No more than eight
tablets are recommended to be taken in any one day.

SERC is not recommended for use in children. As with all drugs, SERC should be kept out of
reach of children.
HOW SUPPLIED:

Scored 4 mg. tablets in bottles of 100 tablets.

Betahistine dihydrochloride
Trade name:
Serc

Active Ingredients:
Betahistine dihydrochloride

Use and Mode of Action:

It is a type of medicine called a histamine analogue. It works by improving blood flow in the
inner ear, which reduces the build up of pressure. It is this pressure in the ear which is thought to
cause the vertigo (dizziness), tinnitus (ringing in the ears) and hearing loss suffered by people
with Meniere’s disease.

Dosage and Frequency (based on adult dosage):

The usual starting dose is 16mg three times a day, preferably with food; the maintenance dose is
24 -48mg a day. It is not recommended for children

Form and Amount:

Tablets, betahistine dihydrochloride 8mg or 16mg

Side Effects:
These are relatively few and include gastro-intestinal (stomach) upset, headache, skin rash and
pruritis (itching)

Cautions:
Asthmatics, those with a history of peptic ulceration, pregnancy & breast-feeding
Contraindictions:
Phaeochromocytoma (high blood pressure due to an adrenal tumour), allergy to betahistine or
any ingredient of serc

Drug Interactions:
None of note

Pregnancy Use:
Serc should be used with caution in pregnancy as advised by your doctor

Onset of Action:
It may take some time to have its full effect, so do not worry if you do not feel better right away.
Your doctor may review the dose you take according to your own needs and symptoms, once the
medicine has had time to work.

Duration of Treatment:
Treatment is long-term

Alternative Medicines:
Medicines used in the management of meniere’s disease include those aimed at treating the
underlying cause of the condition, as well as the associated nausea and vomiting. E.g. diuretics
(“water tablets”) may provide some benefit in vertigo associated with meniere’s disease.