LORAZEPAM TABLETS BP 2.5 MG

Active substance: LORAZEPAM

View full screen / Print PDF » Download PDF ⇩

Transcript
SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Lorazepam Tablets BP 2.5 mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Lorazepam BP 2.5 mg

3

PHARMACEUTICAL FORM
Tablets for oral administration.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
The short-term (2 - 4 weeks) treatment of severe anxiety occurring alone or in
association with insomnia or psychosomatic, organic or psychotic illness.

4.2

Posology and method of administration
Adults:
All indications 1-4mg daily in divided doses, with the lowest effective dose
being used. Treatment should be started with the lowest recommended dose.
The maximum dose should not be exceeded.
Lorazepam should not be used for long term chronic use;
Routine repeat prescriptions should be avoided;
Treatment in all patients should be withdrawn gradually with careful
monitoring and assessment to minimise possible withdrawal symptoms.
Children:
Not recommended for use in children.
Elderly:

At least half the normal adult dose may be effective.
Renal or Hepatic Impairment:
Lower doses may be sufficient in these patients.
Route of Administration:
Oral

4.3

Contraindications
Should not be given to patients
• with a previous history of sensitivity to benzodiazepines, including
Lorazepam tablets and any of its ingredients.



acute pulmonary insufficiency;



sleep apnoea syndrome;



4.4

myasthenia gravis;

severe hepatic impairment

Special warnings and precautions for use
Lorazepam should not be used for long term chronic use as this may result in
the development of tolerance and dependence.
Anaphylactic reactions
Severe anaphylactic/anaphylactoid reactions have been reported with the use
of benzodiazepines. Cases of angioedema involving the tongue, glottis or
larynx have been reported in patients after taking the first or subsequent doses
of benzodiazepines. Some patients taking benzodiazepines have had additional
symptoms such as dyspnoea, throat closing, or nausea and vomiting. Some
patients have required medical therapy in the emergency department. If
angioedema involves the tongue, glottis or larynx, airway obstruction may
occur and be fatal. Patients who develop angioedema after treatment with a
benzodiazepine should not be rechallenged with the drug.
Dependence
Doctors should be aware that repeated doses of Lorazepam over a prolonged
period of time may lead to physical and psychological dependence. The risk of
dependence on Lorazepam is low when used at the recommended dose and
duration, but increases with higher doses and longer term use. The risk of
dependence is further increased in patients with a history of alcoholism or drug
abuse or in patients with significant personality disorders. Therefore, use in
individuals with a history of alcoholism or drug abuse should be avoided.

Once physical dependence has developed, abrupt termination of treatment will
be accompanied by withdrawal symptoms. These may consist of headache,
muscle pain, extreme anxiety, tension, depression, insomnia, restlessness,
confusion, sweating,irritability. and the occurrence of ‘rebound phenomena
whereby the symptoms that led to treatment with benzodiazepines recur in an
enhanced form. These symptoms may be difficult to distinguish from the
original symptoms for which the drug was prescribed.
In severe cases, the following symptoms may occur: derealisation,
depersonalisation, hyperacusis, numbness and tingling of the extremities,
hypersensitivity to light, noise and physical contact, involuntary movements,
vomiting, hallucinations or epileptic seizures (convulsions). Seizures may be
common in patients with pr-existing seizure disorders or who are taking other
drugs that lower the convulsive threshold, such as antidepressants.
Rebound Insomnia and Anxiety:
A transient syndrome whereby the symptoms that led to treatment with a
benzodiazepine recur in an enhanced form, may occur on withdrawal of
treatment. It may be accompanied by other reactions including mood changes,
anxiety, sleep disturbances or restlessness. Since the risk of withdrawal
phenomena/rebound phenomena is greater after abrupt discontinuation of
treatment, it is recommended that the dosage is decreased gradually.
Duration of Treatment
The duration of treatment should be as short as possible. (See indications). It
may be useful to inform the patient when treatment is started that it will be of
limited duration and to explain precisely how the dosage will be progressively
decreased. Moreover it is important that the patient should be aware of the
possibility of rebound phenomena, thereby minimising anxiety over such
symptoms should they occur while the medicinal product is being
discontinued.
There are indications that, in the case of benzodiazepines with a short duration
of action, withdrawal phenomena can become manifest within the dosage
interval, especially when the dosage is high.
Psychiatric and ‘Paradoxical’ Reactions
Benzodiazopines including lorazepam are not intended for the primary
treatment of psychotic illness or depressive disorders and should not be used
alone to treat depression or anxiety associated with depression. The use of
benzodiazepines may have a disinhibiting effect and may release suicidal
tendencies in depressed patients.
Reactions like restlessness, agitation, irritability, aggressiveness, delusion,
rages, nightmares, hallucinations, psychoses, inappropriate behaviour and
other adverse effects are known to occur when using benzodiazepines. They
are more likely to occur in children and the elderly. Should this occur, use of
the drug should be discontinued.
Transient anterograde amnesia or memory impairment has been reported in
association with the use of benzodiazepines. This effect may be advantageous
when Lorazepam is used as a premedicant.

Specific patient groups
Chronic respiratory insufficiency
A lower dose is recommended for patients with chronic respiratory
insufficiency due to the risk of respiratory depression.
Renal and hepatic impairment
Patients with impaired renal or hepatic function should be monitored
frequently and have their dosage adjusted carefully according to patient
response. Lower doses may be sufficient in these patients. The use of
benzodiazepines may worsen hepatic encephalopathy.
Some patients taking benzodiazepines have developed a blood dyscrasia and some
have had elevations in liver enzymes. Periodic haematologic and liver-function
assessments are recommended where repeated courses of treatment are considered
clinically necessary.

As with all CNS-depressants, the use of benzodiazepines may precipitate
encephalopathy in patients with severe hepatic insufficiency. Therefore, use in
these patients is contraindicated.
Hypotension
Although hypotension has occurred only rarely, benzodiazepines should be
administered with caution to patients in whom a drop in blood pressure might
lead to cardiovascular or cerebrovascular complications. This is particularly
important in elderly patients. Dosage reduction is thus recommended in elderly
patients and those suffering from cerebral vascular changes.
Glaucoma
Caution should be used in the treatment of patients with acute narrow-angle
glaucoma.
Alcohol and drug abuse
Benzodiazepines should be used with extreme caution in patients with a
history of alcohol or drug abuse.
Psychiatric disorders
Anxiety or insomnia may be a symptom of several other disorders. The possibility
should be considered that the complaint may be related to an underlying physical or
psychiatric disorder for which there is more specific treatment.
Excipients:
This product contains the excipient, lactose. Patients with rare hereditary problems of
galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
should not take this medicine.

4.5

Interaction with other medicinal products and other forms of interaction
Not recommended: Concomitant intake with alcohol.
The sedative effect may be enhanced when the product is used in combination
with alcohol. This affects the ability to drive or use machines.

Take into account: Combination with CNS depressants
Enhancement of the central depressive effect may occur in cases of
concomitant use with barbiturates, antipsychotics (neuroleptics), hypnotics,
anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anti-epileptic
(convulsants) drugs, anaesthetics and sedative antihistamines.
Concurrent administration of lorazepam with sodium valproate may result in
reduced clearance (20% - 40%) and increased plasma concentrations of
lorazepam. Therefore clinical monitoring is advised and lorazepam dosage
should be reduced when appropriate.
Concurrent administration of lorazepam with probenecid may result in reduced
clearance, increased elimination half-life and increased concentrations of
lorazepam. Clinical monitoring is recommended and the lorazepam dosage
should be reduced when appropriate.
In the case of narcotic analgesics enhancement of the euphoria may also occur
leading to an increase in psychic dependence.
Compounds which inhibit certain hepatic enzymes (particularly cytochrome
P450) may enhance the activity of benzodiazepines. To a lesser degree this
also applies to benzodiazepines that are metabolised only by conjugation.
Concomitant use of clozapine and lorazepam may produce marked sedation,
excessive salivation and ataxia.
Administration of theophylline or aminophylline may reduce the sedative effects of
benzodiazepines, including lorazepam.

4.6

Pregnancy and lactation
Lorazepam should not be used during pregnancy, especially during the first and last
trimesters, unless in the judgement of the physician such administration is clinically
justifiable. Benzodiazepines may cause foetal damage when administered to pregnant
women.

If lorazepam is prescribed to a woman of child bearing potential, she should be
warned to contact her physician regarding discontinuation of the product if she
intends to become or suspects that she is pregnant.
If, for compelling medical reasons, the product is administered during the late
phase of pregnancy or during labour, effects on the neonate, such as
hypothermia, hypotonia and moderate respiratory depression, can be expected,
due to the pharmacological action of the compound.
Moreover, infants born to mothers who took benzodiazepines chronically
during the latter stages of pregnancy may have developed physical dependence
and may be at some risk for developing withdrawal symptoms in the postnatal
period.
Symptoms such as hypotonia, hypothermia, respiratory depression, apnoea,
feeding problems and impaired metabolic response to cold stress have been
reported in neonates born of mothers who have received benzodiazepines
during the late phase of pregnancy or at delivery.

Since benzodiazepines transfer to breast milk, lorazepam should not be given
to breast feeding mothers unless the expected benefit to the woman outweighs
the potential risk to the infant.
4.7

Effects on ability to drive and use machines
Sedation, amnesia, impaired concentration and impaired muscular function
may adversely affect the ability to drive or to use machines. If insufficient
sleep duration occurs, the likelihood of impaired alertness may be increased.
(See also Interactions). Patients that are affected should be advised to avoid
driving or operating machinery.

4.8

Undesirable effects
Adverse reactions are listed in the table in CIOMS frequency categories:
Very common:



Common:



Uncommon:



Rare:



Very rare:

10%
1% and < 10%
0.1% and < 1%
0.01% and < 0.1%

< 0.01%

Undetermined: Insufficient data to calculate significant frequencies.

Common (
1% and <
10%)



Very
common (
10%)

Uncommon
( 0.1% and
< 1%)

Undetermined





System Organ
Class and
Frequency
Blood and
lymphatic
system
disorders

Thrombocytopenia,
agranulocytosis,
pancytopenia

Immune system
disorders

Hypersensitivity reactions,
anaphylactic reactions,
angioedema.

Endocrine
disorders

Syndrome of Inappropriate
Antidiuretic Hormone
Secretion (SIADH)

Metabolism &
nutrition
disorders

Hyponatraemia

Psychiatric
disorders

Confusion,
depression,
unmasking
of
depression.

Disinhibition, euphoria,
suicidal ideation/attempt,
Paradoxical reactions2,
including anxiety, agitation,
excitation, hostility,
aggression, rage, sleep
disturbances/insomnia,

Common (
1% and <
10%)



Very
common (
10%)

Uncommon
( 0.1% and
< 1%)

Undetermined





System Organ
Class and
Frequency

sexual arousal and
hallucinations.
Nervous system
disorders*

Sedation,
drowsiness,

Ataxia,
dizziness

Extrapyramidal symptoms,
tremor, vertigo, visual
disturbances (including
diplopia and blurred vision),
dysarthria/slurred speech,
headache,
convulsions/seizures,
amnesia1, coma

Vascular
disorders

Hypotension

Respiratory,
thoracic and
mediastinal
disorders+

Respiratory depression,
apnoea, worsening of sleep,
worsening of obstructive
pulmonary disease

Gastrointestinal
disorders

Nausea,

Constipation

Hepatobiliary
disorders

Increase in bilirubin,
increase in liver
transaminases, increase in
alkaline phosphatase

Skin and
subcutaneous
tissue disorders

Allergic skin reactions,
alopecia

Reproductive
system and
breast disorders

General
disorders

Change in
libido,
impotence,
decreased
orgasm
Fatigue

Muscle
weakness,
asthenia

Hypothermia

* Benzodiazepine effects on the CNS are dose dependent, with more severe CNS
depression occurring with higher doses.

+ The extent of respiratory depression with benzodiazepines is dose dependent
with more severe depression occurring with high doses.
1
Transient anterograde amnesia or memory impairment may occur using
therapeutic doses, the risk increasing at higher doses (see section 4.4).
Amnesic effects may be associated with inappropriate behaviour.
2
Paradoxical reactions are more likely to occur in children and the elderly (see
section 4.4).
Dependence

Use (even at therapeutic doses) may lead to the development of physical
dependence: discontinuation of the therapy may result in withdrawal or
rebound phenomena. (See warnings and precautions).
Abuse of benzodiazepines has been reported.

4.9

Overdose
As with other benzodiazepines, overdose should not present a threat to life
unless combined with other CNS depressants (including alcohol).
Symptoms
Overdose of benzodiazepines is usually manifested by degrees of central
nervous system depression ranging from drowsiness to coma. In mild cases,
symptoms include drowsiness, mental confusion and lethargy, in more serious
cases, symptoms may include ataxia, hypotonia, hypotension, respiratory
depression, rarely coma and very rarely death.
Treatment
In the management of overdose with any medicinal product, it should be borne
in mind that multiple agents may have been taken.
Following overdose with oral benzodiazepines, vomiting should be induced
(within one hour) if the patient is conscious or gastric lavage undertaken with
the airway protected if the patient is unconscious. If there is no advantage in
emptying the stomach, activated charcoal should be given to reduce
absorption.
Special attention should be paid to respiratory and cardiovascular functions
in intensive care. This will be mainly supportive including monitoring of
vital signs and close observation of the patient. A clear/adequate airway
should be maintained (including during sleep) and assisted respiration used
as needed. Hypotension, though unlikely, may be controlled with
noradrenaline. Lorazepam is poorly dialysable.
The benzodiazepine antagonist, flumazenil, may be useful in hospitalised
patients for the management of benzodiazepine overdosage. Flumazenil
product information should be consulted prior to use. The physician should be
aware of a risk of seizure in association with flumazenil treatment, particularly
in long-term benzodiazepine users and in tricyclic antidepressant overdose..

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Anxiolytic benzodiazepine derivatives;
ATC code: N05BA06

Lorazepam is a short-acting benzodiazepine anxiolytic with sedative, muscle
relaxant and amnesic properties.

5.2

Pharmacokinetic properties
Lorazepam is rapidly absorbed from the gastro intestinal tract and is
metabolised by a simple one-step process to a pharmacologically inactive
glucuronide. The elimination half-life is about 12 hours so that steady state
plasma levels are quickly reached, and there is minimal risk of excessive
accumulation, giving a wide margin of safety.

5.3

Preclinical safety data
Not applicable

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose powder BP,
Maize starch BP,
Povidone BP,
Water BP,
Sodium starch glycollate (primojel) BP,
Colloidal silicon dioxide (aerosil 200) USP,
Magnesium stearate BP,
Anstead dispersed orange No. 11348 (E110)

6.2

Incompatibilities
No major incompatibilities other than those reported under 4.5 above.

6.3

Shelf life
36 months

6.4

Special precautions for storage
Store in a cool, dry place and protect from light

6.5

Nature and contents of container
Polypropylene tubular container with an open end equipped to accept a
polyethylene closure with a tamper-evident tear strip containing, 7, 14, 21, 28,
30, 56, 60, 84, 90, 100, 112, 120, 250, 500 and 1000 tablets.

6.6

Special precautions for disposal
No special instructions.

7

MARKETING AUTHORISATION HOLDER
Norton Healthcare Ltd.,
T/A IVAX Pharmaceuticals
Albert Basin,
Royal Docks,
London, E16 2QJ.

8

MARKETING AUTHORISATION NUMBER(S)
PL 00530/0081

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
01/04/1981 / 24/02/2009

10

DATE OF REVISION OF THE TEXT
05/10/2010

Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

Hide
(web4)