LOPERAMIDE 2MG TABLETS

Active substance: LOPERAMIDE HYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Loperamide 2mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 2mg loperamide hydrochloride.
Excipients: each tablet contains 100mg of lactose monohydrate.
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Light green coloured capsule shaped, biconvex uncoated tablets, plain on one side
and score line on other side.
The score line is only to facilitate breaking for ease of swallowing and not to divide
into equal doses.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

For the symptomatic treatment of acute diarrhoea of any aetiology including acute
exacerbations of chronic diarrhoea for periods of up to 5 days in adults and children
over 6 years. For the symptomatic treatment of chronic diarrhoea in adults.

4.2

Posology and method of administration
ACUTE DIARRHOEA
Adults and children over 6 years of age:
Two tablets initially, followed by one tablet after each loose stool. The usual dose is
3-4 tablets a day. The total daily dose should not exceed 8 tablets.

Children between the ages of 2 and 5 years:

These tablets are not recommended for children between 2 and 5 years.An alternative
formulation (Oral solution/liquid) of Loperamide suitable for children should be
administered in this patient population.
Children under 2 years of age:
Loperamide is contraindicated in children under 2 years of age.
CHRONIC DIARRHOEA
Adults:
Studies have shown that patients may need widely differing amounts of loperamide.
The starting dose should be between two and four tablets per day in divided doses,
depending on severity. If required, this dose can be adjusted according to result up to
a maximum of eight tablets daily.
Having established the patient's daily maintenance dose, the tablets may be
administered on a twice daily regimen. Tolerance has not been observed and therefore
subsequent dosage adjustment should be unnecessary.

USE IN ELDERLY
No dose adjustment is required for the elderly.
RENAL IMPAIRMENT
No dose adjustment is required for patients with renal impairment.
HEPATIC IMPAIRMENT
Although no pharmacokinetic data are available in patients with hepatic impairment,
Loperamide 2mg Tablets should be used with caution in such patients because of
reduced first pass metabolism (see 4.4 Special warnings and precautions for use).
Method of administration
Oral use.

4.3

Contraindications
Loperamide 2mg Tablets are contraindicated in:
• patients with a known hypersensitivity to loperamide hydrochloride or to any of the
excipients.
• children less than 6 years of age.
• when inhibition of peristalsis is to be avoided due to the possible risk of significant
sequelae including ileus, megacolon and toxic megacolon, in particular:
Loperamide hydrochloride must be discontinued promptly when ileus or constipation
are present or when abdominal distension develops, particularly in severely
dehydrated children,
- in patients with acute ulcerative colitis,
- in patients with bacterial enterocolitis caused by invasive organisms including
Salmonella, Shigella, and Campylobacter,
- in patients with pseudomembranous colitis associated with the use of broadspectrum antibiotics.
Loperamide 2mg Tablets should not be used alone in acute dysentery, which is
characterised by blood in stools and elevated body temperatures.

4.4

Special warnings and precautions for use

Treatment of diarrhoea with Loperamide is only symptomatic. Whenever an
underlying etiology can be determined, specific treatment should be given when
appropriate.The priority in acute diarrhoea is the prevention or reversal of fluid and
electrolyte depletion. This is particularly important in young children and in frail and
elderly patients with acute diarrhoea. Use of Loperamide 2mg Tablets does not
preclude the administration of appropriate fluid and electrolyte replacement therapy.
Since persistent diarrhoea can be an indicator of potentially more serious conditions,
Loperamide 2mg Tablets should not be used for prolonged periods until the
underlying cause of the diarrhoea has been investigated.
Loperamide HCl should not be given to children aged 2 to 6 years of age without
medical prescription and supervision. Loperamide 2mg Tablets must be used with
caution when the hepatic function necessary for the drug's metabolism is defective (eg
in cases of severe hepatic disturbance), as this might result in a relative overdose
leading to CNS toxicity.
Patients with AIDS treated with Loperamide 2mg Tablets for diarrhoea should have
therapy stopped at the earliest signs of abdominal distension. There have been
isolated reports of obstipation with an increased risk for toxic megacolon in AIDS
patients with infectious colitis from both viral and bacterial pathogens treated with
loperamide hydrochloride.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption should not take this medicine because
it contains lactose.
In acute diarrhoea, if clinical improvement is not observed within 48 hours, the
administration of Loperamide hydrochloride should be discontinued and patients
should be advised to consult their physician.
Although no pharmacokinetic data are available in patients with hepatic impairment,
Loperamide hydrochloride should be used with caution in such patients because of
reduced first pass metabolism.

4.5

Interaction with other medicinal products and other forms of interaction
Non-clinical data have shown that loperamide is a P-glycoprotein substrate.
Concomitant administration of loperamide (16 mg single dose) with quinidine, or
ritonavir, which are both P-glycoprotein inhibitors, resulted in a 2 to 3-fold increase
in loperamide plasma levels. The clinical relevance of this pharmacokinetic
interaction with P-glycoprotein inhibitors, when loperamide is given at recommended
dosages (2 mg, up to 16 mg maximum daily dose), is unknown.
The concomitant administration of loperamide (4 mg single dose) and itraconazole,
an inhibitor of CYP3A4 and P-glycoprotein, resulted in a 3 to 4-fold increase in
loperamide plasma concentrations. In the same study a CYP2C8 inhibitor,
gemfibrozil, increased loperamide by approximately 2-fold. The combination of
itraconazole and gemfibrozil resulted in a 4-fold increase in peak plasma levels of
loperamide and a 13-fold increase in total plasma exposure. These increases were not
associated with central nervous system (CNS) effects as measured by psychomotor
tests (i.e. subjective drowsiness and the Digit Symbol Substitution Test).
The concomitant administration of loperamide (16 mg single dose) and ketoconazole,
an inhibitor of CYP3A4 and P-glycoprotein, resulted in a 5-fold increase in
loperamide plasma concentrations. This increase was not associated with increased
pharmacodynamic effects as measured by pupillometry.

The results of one published pharmacokinetic study suggested that the concomitant
administration of loperamide with oral desmopressin may result in a 3-fold increase
of desmopressin plasma concentrations presumably due to slower gastrointestinal
motility, although no clinical effects were reported.
It is expected that drugs with similar pharmacological properties may potentiate
loperamide's effect and that drugs that accelerate gastrointestinal transit may decrease
its effect.

4.6

Fertility, pregnancy and lactation
Safety in human pregnancy has not been established although studies in animals have
not demonstrated any teratogenic effects or embryotoxic properties, the anticipated
therapeutic benefits should be weighed against potential hazards before loperamide
HCl is given during pregnancy, especially during the first trimester. As with other
drugs, it is not advisable administer Loperamide 2mg Tablets in pregnancy.
Small amounts of loperamide may appear in human breast milk. Therefore,
Loperamide 2mg Tablets is not recommended during breast-feeding.
Women who are pregnant or breast feeding infants should therefore be advised to
consult their doctor for appropriate treatment.

4.7

Effects on ability to drive and use machines
Tiredness, dizziness, or drowsiness may occur in the setting of diarrheal syndromes
when diarrhoea is treated with Loperamide 2mg Tablets. Therefore, it is advisable to
use caution when driving a car or operating machinery. See section 4.8 Undesirable
Effects.

4.8

Undesirable effects

Adults and children aged 12 years



The safety of loperamide HCl was evaluated in 3076 adults and children aged 12
years who participated in 31 controlled and uncontrolled clinical trials of loperamide
HCl used for the treatment of diarrhoea. Of these, 26 trials were in acute diarrhoea
(N=2755) and 5 trials were in chronic diarrhoea (N=321).



The most commonly reported (i.e., 1% incidence) adverse drug reactions (ADRs) in
clinical trials with loperamide HCl in acute diarrhoea were: constipation (2.7%),
flatulence (1.7%), headache (1.2%) and nausea (1.1%). In clinical trials in chronic
diarrhoea, the most commonly reported (i.e., 1% incidence) ADRs were: flatulence
(2.8%), constipation (2.2%), nausea (1.2%) and dizziness (1.2%).





Table 1 displays ADRs that have been reported with the use of loperamide HCl from
either clinical trial (in acute or chronic diarrhoea or both) or post-marketing
experience.
The frequency categories use the following convention: very common ( 1/10);
common ( 1/100 to <1/10); uncommon ( 1/1,000 to <1/100); rare ( 1/10,000 to
<1/1,000); and very rare (<1/10,000).









Indication

System Organ Class

Chronic
Acute
Diarrhoea Diarrhoea
(N=2755) (N=321)

Immune System Disorders
Hypersensitivity reactiona,
Anaphylactic reaction (including
Anaphylactic shock)a, Anaphylactoid
reactiona
Nervous System Disorders
Headache
Common Uncommon
Dizziness
Uncommon Common
Somnolencea
Loss of consciousnessa, Stupora,
Depressed level of consciousnessa,
Hypertoniaa, Coordination
abnormalitya
Eye Disorders
Miosisa

Acute + Chronic
Diarrhoea and
postmarketing
experience

Rare

Common
Common
Uncommon
Rare

Rare

Gastrointestinal Disorders
Constipation, Nausea, Flatulence
Common Common
Common
Abdominal
pain,
Abdominal
Uncommon
Uncommon Uncommon
discomfort, Dry mouth
Abdominal pain upper, Vomiting
Uncommon
Uncommon
Dyspepsia
Uncommon
Uncommon
Ileusa (including paralytic ileus),
Rare
Megacolona (including toxic
megacolonb),
Abdominal distension, Glossodynia
Rare
Rare
Skin and Subcutaneous Tissue Disorders
Rash
Uncommon
Uncommon
Skin and Subcutaneous Tissue Disorders
Bullous eruptiona (including
Stevens-Johnson syndrome, Toxic
Rare
epidermal necrolysis and Erythema
multiforme), Angioedemaa, Urticariaa,
Pruritusa
Renal and Urinary Disorders
Urinary retentiona
Rare
General Disorders and Administration Site
Conditions
Fatiguea
Rare
a: Inclusion of this term is based on post-marketing reports for loperamide HCl. As the
process for determining post marketing ADRs did not differentiate between chronic and acute
indications or adults and children, the frequency is estimated from all clinical trials with
loperamide HCl combined, including trials in children 12 years (N=3683).
b: See section 4.4 Special Warnings and Special Precautions for use.



Indication

System Organ Class

Chronic
Acute
Diarrhoea Diarrhoea
(N=2755) (N=321)

Acute + Chronic
Diarrhoea and
postmarketing
experience

c: Reported for the orodispersible tablet only.
For clinical trial ADRs where no frequency is presented, the term was not observed or
considered an ADR for this indication.
Paediatric population
The safety of loperamide HCl was evaluated in 607 patients aged 10 days to 13 years who
participated in 13 controlled and uncontrolled clinical trials of loperamide HCl used for the
treatment of acute diarrhoea. In general, the ADR profile in this patient population was similar
to that seen in clinical trials of loperamide HCl in adults and children aged 12 years and over.

4.9

Overdose
Symptoms
In case of overdose the following effects may be observed (including relative
overdose due to hepatic dysfunction), CNS depression (stupor, coordination
abnormality, respiratory depression) constipation, urinary retention, ileus and
neurological symptoms (miosis, muscular hypertonia, somnolence and bradypnoea).
Children may be more sensitive to CNS effects than adults.
Treatment
If intoxication is suspected, naloxone may be given as an antidote. Since the duration
of action of loperamide is longer than that of naloxone (1 to 3 hours), repeated
treatment with naloxone might be indicated, the patient should be kept under constant
observation for at least 48 hours in order to detect any possible depression of the
central nervous system. Children, and patients with hepatic dysfunction, may be more
sensitive to CNS effects. Gastric lavage, or induced emesis and or enema or laxatives
may be recommended.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Antipropulsives, ATC code: A07DA03
Loperamide binds to the opiate receptor in the gut wall, reducing propulsive
peristalsis and increasing intestinal transit time. Loperamide increases the tone of the
anal sphincter.

In a double blind randomised clinical trial in 56 patients with acute diarrhoea
receiving loperamide, onset of anti-diarrhoeal action was observed within one hour
following a single 4 mg dose. Clinical comparisons with other antidiarrhoeal drugs
confirmed this exceptionally rapid onset of action of loperamide.

5.2

Pharmacokinetic properties
The half-life of loperamide in man is 10.8 hours with a range of 9-14 hours. Studies
on distribution in rats show high affinity for the gut wall with preference for binding
to the receptors in the longitudinal muscle layer. Loperamide is well absorbed from
the gut, but is almost completely extracted and metabolised by the liver where it is
conjugated and excreted via the bile. Due to its high affinity for the gut wall and its
high first pass metabolism, very little loperamide reaches the systemic circulation.

5.3

Preclinical safety data
No relevant information additional to that contained elsewhere in the Summary of
Product Characteristics.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose monohydrate
Maize starch
Talc
Magnesium stearate
Povidone
Brilliant Blue (E133)
Quinoline Yellow (E104)
Colloidal anhydrous silica
Sodium starch glycolate

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
3 years

6.4

Special precautions for storage
This medicine product does not require any special storage instructions.

6.5

Nature and contents of container

Blisters composed of PVC/PVDC film, which is clear, non-toxic, transparent and
thermoformable and of aluminium foil.
Pack size: 30 tablets.
Not all pack sizes may be marketed
6.6

Special precautions for disposal
No special requirements.
Any unused product or waste material should be disposed of in accordance with local
requirements.

7

MARKETING AUTHORISATION HOLDER
Marketing Authorisation Holder:
Morningside Healthcare Limited
115 Narborough Road
Leicester, LE3 0PA
United Kingdom.

8

MARKETING AUTHORISATION NUMBER(S)
PL 20117/0087

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
25/02/2011

10

DATE OF REVISION OF THE TEXT
19/11/2012

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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.

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