LEXOTANIL

Roche
Composition
Active ingredient: bromazepam.
Tablets (scored) of 1.5mg (white), 3mg (pink), and
6mg (green).
Excipients: Tablets of 1.5mg: excip, pro compr.; tab
lets of 3mg: colorant (E127), excip. pro compr.; tab
lets of 6mg: colorant (E312), excip. pro compr.
Properties
In low dosage, Lexotanil selectively reduces anxiety,
tension, and nervousness. In high dosage, sedative
and musclerelaxant properties appear.
Pharmacokinetics
Absorption
Peak plasma concentrations are reached within one
to two hours of oral administration of bromazepam.
The absolute bioavailability of the unchanged sub
stance is 84%.

impairments of various organs caused or exacerbat

ed by anxiety and tension:
Cardiovascular and Respiratory Systems:
(e.g. pseudoangina pectoris, precordial anxiety,
tachycardia, emotiogenic hypertension, dyspnea,
and hyperventilation);
Gastrointestinal tract: (e.g. irritable bowel syndrome,
ulcerative colitis, epigastric pain, spasm, bloating,
and diarrhea);
Urogenital tract: (e.g. irritable bladder, urinary fre
quency, dysmenorrhea);
Other Psychosomatic Disturbances: (e.g. psycho
genic headache, psychogenic dermatoses).
Lexotanil is also suitable for treatment of anxiety
and tension states due to chronic organic disease
and as an adjuvant to psychotherapy in psychoneu
rosis.

Contraindications
Distribution
On average, 70% of bromazepam is bound to plas Lexotanil is contraindicated in patients with known
hypersensitivity to benzodiazepines, severe respi
ma proteins.
ratory failure, sleep apnea syndrome, myasthenia
Metabolism
gravis, and severe liver failure (benzodiazepines are
Bromazepam is metabolized in the liver.
contraindicated in severe liver failure because they
Quantitatively, two metabolites predominate: 3- can exacerbate hepatic encephalopathy).
hydroxybromazepam and 2(2 amino5 bromo- 3- Benzodiazepines are not suitable for the primary
hydroxybenzoyl) pyridine.
treatment of psychotic disorders. Benzodiazepines
Elimination
should not be used as sole agents for the treatment
Bromazepam has an elimination halflife of 1020 of depression or anxiety associated with depres
hours, but the halflife may be longer in elderly sion (this can lead the patient to commit suicide).
subjects. The metabolites are excreted in the urine Patients known or presumed to be dependent on
mainly in conjugated form.
alcohol, medicines, or drugs should not take benzo
diazepines.
Indications
Emotional disturbances: anxiety and tension states, Side Effects
as adjuvant therapy for anxiety in depressed The following side effects can occur: tiredness,
patients, nervous tension, restlessness, and anxiety drowsiness, muscle weakness, blunting of feelings,
and tensionrelated insomnia.
reduced alertness, confusion, headache, dizziness,
As an adjuvant to treatment of an underlying dis ataxia, and diplopia. These effects occur predomi
ease responsible for functional or psychosomatic nantly at the start of treatment and generally dis

appear with continuation of treatment. There have

been occasional reports of gastrointestinal distur
bances, loss of libido, and skin reactions.
Therapeutic dosage may lead to anterograde amne
sia, the risk of which increases with increasing dos
age. The amnesia may be accompanied by inappro
priate behavior. Preexisting depression may become
manifest during treatment with benzodiazepines.
Paradoxical reactions such as restlessness, agita
tion, irritability, aggressiveness, delusions, fits of rage,
nightmares, hallucinations, psychoses, inappropri
ate behavior, and other behavioral disturbances are
known to occur with use of benzodiazepines and
benzodiazepinelike substances (see Precautions).
Such reactions, which occur more commonly in chil
dren and elderly patients, call for discontinuation of
treatment. Prolonged use (even in therapeutic doses)
can lead to physical dependence. Discontinuation
of the drug can then lead to the appearance of with
drawal or rebound phenomena (see Precautions).
Psychologic dependence can also occur. There are
reports of abuse of benzodiazepines.
Precautions
Relative Restrictions on Use
Caution is required in patients with chronic respiratory
failure, as they are at risk of respiratory depression.
Alertness, Reactive Capacity
Sedation, amnesia, and impairment of muscle func
tion can impair the ability to drive a motor vehicle or
operate machines. These effects are exacerbated
by alcohol.
Dependence
Use of benzodiazepines can lead to dependence.
This risk increases with dose and duration of
treatment and is higher in predisposed patients.
Withdrawal phenomena occur especially after
abrupt discontinuation and in milder cases are lim
ited to tremor, restlessness, insomnia, anxiety,
headache, and impairment of concentration, though
symptoms such as sweating, muscle pain, abdomi
nal pain, disturbances of perception, and in rare
cases delirium and convulsions may occur.

Depending on the duration of action of the sub

stance concerned, withdrawal phenomena com
mence a few hours to a week or more after discon
tinuation of treatment. In order to minimize the risk
of dependence, benzodiazepines should be pre
scribed only after a careful consideration of the indi
cation and should be taken for as short a period as
possible (generally no longer than four weeks when
used as a hypnotic, for example). The need for con
tinuation of treatment should be reviewed regular
ly. The riskbenefit relationship of more prolonged
treatment is less clear hence it is indicated only in
certain patients (e.g. those with panic attacks).
In order to avoid withdrawal phenomena the drug
should be discontinued by tapering off the dose in
all patients. Should withdrawal phenomena occur,
close medical monitoring and support of the patient
are required.
Pregnancy and Lactation
The safety of bromazepam in pregnant women has
not been established. Spontaneous reports do not
suggest a higher incidence of adverse drug reac
tions than would be expected in a similar untreated
group of female patients. A number of studies refer
to an increased risk of congenital malformations in
the child when tranquilizers (diazepam, meprobam
ate, and chlordiazepoxide) are taken during the first
trimester of pregnancy. Bromazepam should not be
taken during pregnancy unless there is a compelling
indication for its use and no safer therapeutic alter
native is available.
Women of childbearing age who are prescribed the
drug should be instructed to inform the doctor if they
plan to become pregnant, or suspect that they may be
pregnant, in order that the drug can be discontinued.
Bromazepam may be taken during the last trimes
ter of pregnancy or during confinement only if there
is a compelling indication for its use, as because of
its pharmacologic action effects such as hypother
mia, hypotension, and moderately severe respira
tory depression are to be expected in the neonate.
Furthermore, children of mothers who took benzodi
azepines regularly during late pregnancy may have

developed physical dependence and are therefore at

risk of developing withdrawal phenomena after birth.
As benzodiazepines are excreted in breast milk,
nursing mothers should not take Lexotanil.
Overdosage
As with other benzodiazepines, intentional or acci
dental overdosage of Lexotanil is seldom life-threat
ening unless other CNS depressants (including
alcohol) have been taken simultaneously.
Overdosage of benzodiazepines generally mani
fests itself in the form of CNS depression ranging
from drowsiness to coma. In mild cases symptoms
such as drowsiness, contusion, and lethargy occur.
In most cases it is sufficient to monitor vital functions
and await recovery.
Higher overdoses, especially in combination with other
centrally acting drugs, can result in ataxia, reduced
muscle tonus, hypotension, respiratory depression, in
rare cases coma, and very rarely death.
In the treatment of overdoses of medications it
should be borne in mind that a number of substanc
es may have been taken. Provided that they are
conscious, patients who have taken an overdose of
benzodiazepines should be made to vomit (within an
hour); unconscious patients should undergo gastric
lavage with maintenance of a clear airway. Where
no benefit is to be expected from evacuation of the
stomach, activated charcoal should be administered
to reduce intestinal absorption. The patients respi
ration and cardiac function should be particularly
closely monitored. Anexate (flumazenil) can be use
ful as an antagonist.

antiepileptics, sedative antihistamines, or anesthet

ics, its CNS sedative effect may be increased. There
is an increased risk of respiratory depression. In the
case of narcotic analgesics euphoria, and hence
also psychologic dependence, may be increased.
In patients taking muscle relaxants the risk of mus
cle weakness is increased.
Although no such effect is known to occur with
Lexotanil, drugs that inhibit certain hepatic enzymes
(in particular cytochrome P450) can potentiate the
effect of benzodiazepines that are metabolized by
these enzymes.
By increasing its rate of absorption, cisapride
can cause transient potentiation of the effects of
Lexotanil.

Dosage and Administration

Standard Dosage
Average dose for outpatient therapy: 1.53mg up to
three times daily.
Severe cases, especially in hospitals: 612mg two
or three times daily.
These amounts are general recommendations,
and dosage should be individually determined.
Treatment of outpatients should begin with low
doses, gradually increasing to the optimum level.
The duration of treatment should be as short as pos
sible. The patients condition should be reassessed
at regular intervals and the need for continued treat
ment determined, especially if the patient no longer
has any symptoms. In general, the total duration of
treatment should not exceed 812 weeks including a
taperingoff period. In certain cases treatment may
Stability
need to be continued beyond the maximum recom
This medicine should not be used after the expiry mended duration, but only after a careful reassess
date (EXP) shown on the pack.
ment of the patients condition and the indications.
Drug Interactions
As with all psychoactive substances, the effect
of Lexotanil may be intensified by alcohol.
Simultaneous intake of alcohol should be avoided.
When Lexotanil is combined with other centrally act
ing drugs such as antidepressants, hypnotics, nar
cotic analgesics, neuroleptics, anxiolytics/sedatives,

Special Dosage Instructions

Lexotanil is generally not indicated in children.
Should the doctor nevertheless consider treatment
with Lexotanil to be indicated, the dosage should be
adjusted to the lower body weight of the child.
Elderly patients and patients with disturbances of
hepatic and/or renal function require lower doses

because of differences in reactivity and pharmaco

kinetics.
At the start of treatment the patient should be
checked regularly in order to keep the dose and/or
dose frequency as low as possible and avoid the
risk of overdosage of the drug as a result of accu
mulation.
Duration of Treatment
At the start of treatment it may be useful to inform
the patient that the duration of treatment will be lim
ited and that the dose will be tapered off at the end
of treatment.
It is important that the patient be aware that rebound
and withdrawal phenomena may occur during with
drawal of the drug. Withdrawal phenomena can also
occur when a benzodiazepine is replaced by anoth
er benzodiazepine with a significantly shorter elimi
nation halflife.