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LOPERAMIDE GALPHARM 2 MG CAPSULES HARD

Active substance(s): LOPERAMIDE HYDROCHLORIDE / LOPERAMIDE HYDROCHLORIDE / LOPERAMIDE HYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Loperamide Galpharm 2mg Capsules, Hard

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Loperamide Hydrochloride 2 mg.
Lactose Monohydrate 146 mg per capsule.
For full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Capsule, hard [Capsule].
Opaque blue cap and grey body, hard gelatin capsule containing white powder.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For symptomatic treatment of acute diarrhoea in adults and children aged 12 years
and over.

4.2

Posology and method of administration
Posology
Adults and children over 12 years of age:
Two capsules to be taken initially, followed by one capsule after each loose
motion, up to a maximum of six capsules in any 24 hours.

Children under 12 years of age:
Not recommended
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 [product name] should be used with caution in such patients
because of reduced first pass metabolism (see section 4.4 Special warnings
and precautions for use).
Method of administration
Oral use.

4.3

Contraindications
Hypersensitivity to the active substance or to any of the excipient listed in
section 6.1.
When inhibition of peristalsis is to be avoided due to the possible risk of
significant sequelae including ileus, megacolon, toxic megacolon and certain
poisonings in particular:


Children less than 12 years of age.



When ileus or constipation are present or when abdominal distension
develops



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
broad-spectrum antibiotics.

Loperamide hydrochloride 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 hydrochloride 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 hydrochloride should not be used for prolonged
periods until the underlying cause of the diarrhoea has been investigated.
loperamide hydrochloride 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 hydrochloride for diarrhoea
should have therapy stopped at the earliest signs of abdominal distension.
There have been isolated reports of 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.
When no clinical change is observed in the acute diarrhoea within 48 hours,
the administration of loperamide must be interrupted and the patient must be
advised to consult his doctor.

[product name] should not be used in chronic diarrhoea, which requires
follow-up by a physician.
Treatment with [product name] must be interrupted immediately when
obstipation, abdomnial distension or subileus develops.
4.5

Interaction with other medicinal products and other forms of interaction
Non-clinical data have shown that loperamide hydrochloride is a P-glycoprotein
substrate. Furthermore, loperamide is mainly metabolisedby CYP3A4 and CYP2C8.
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 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 although no clinical effects were reported.
Possible interactions may occur with drugs that delay intestinal peristalsis (for
instance anti-cholinergic drugs) because the effects of loperamide could be enhanced.
Administration of itraconazole with loperamide (4 mg single dose) increased
loperamide plasma levels 3- to 4-fold. In addition, gemfibrozil, a CYP2C8 inhibitor,
increased the AUC of loperamide 2-fold. Concomitant use of itraconazole and
gemfibrozil with loperamide raised the mean Cmax and AUC of loperamide about 2and 13-fold, respectively. This increase did not lead to measurable CNS effects.
The concomitant administration of loperamide (16mg 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 clinical relevance of these pharmacokinetic interactions, when loperamide is
given at recommended dosages (2 mg, up to 12 mg maximum daily dose), is
unknown.

4.6

Fertility, pregnancy and lactation
Pregnancy
A limited amount of data from the use of loperamide in pregnant women is
available. In one of two epidemiological studies the use of loperamide during
early pregnancy suggested a possible moderate increased risk for hypospadia,
however, an increased risk for major malformations could not be identified.

Animal studies do not indicate direct or indirect harmful effects with respect to
reproductive toxicity (see section 5.3). Safety in human pregnancy has not
been established, although from animal studies there are no indications that
loperamide HCl possesses any teratogenic or embryotoxic properties.
If possible the use of loperamide should be avoided during the first trimester
of pregnancy, however, it may be used during the second and third trimester of
pregnancy
Breast-feeding
Small amounts of loperamide may appear in human breast milk. Therefore,
this medicine 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.
Fertility
Only high doses of loperamide hydrochloride affected female fertility in nonclinical studies (see section 5.3).

2B

4.7

Effects on ability to drive and use machines

Loperamide hydrochloride has moderate influence on the ability to drive and use
machines. Loss of consciousness, depressed level of consciousness, tiredness,
dizziness or drowsiness may occur when diarrhoea is treated with loperamide
hydrochloride.
Therefore, it is advisable to use caution when driving or operating machinery. (See
section 4.8 Undesirable effects).
2B

4.8

Undesirable effects

Adults and children aged ≥ 12 years
The safety of loperamide hydrochloride was evaluated in 2755 adults and children
aged ≥ 12 years who participated in 26 controlled and uncontrolled clinical trials of
loperamide hydrochoride used for the treatment of acute diarrhoea.
U

The most commonly reported (i.e. ≥1% incidence) adverse drug reactions (ADRs) in
clinical trials with loperamide hydrochoride in acute diarrhoea were: constipation
(2.7%), flatulence (1.7%), headache (1.2%) and nausea (1.1%).
Table 1 displays ADRs that have been reported with the use of loperamide
hydrochoride from either clinical trial (acute diarrhoea) 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).
Table 1

Adverse Drug reactions

System Organ
Class

Indication
Common

Uncommon

Headache
Dizziness

Somnolencea

Immune System
Disorders

Nervous System
Disorders

Eye Disorders
Gastrointestinal
Disorders

Skin and
Subcutaneous Tissue
Disorders

Renal and Urinary
Disorders

Constipation
Nausea
Flatulence

Abdominal pain
Abdominal
discomfort
Dry mouth
Abdominal pain
upper
Vomiting
Dyspepsiaa
Rash

Rare
Hypersensitivity
reactiona
Anaphylactic
reaction (including
Anaphylactic
shock)a
Anaphylactoid
reactiona
Loss of
consciousnessa
Stupora
Depressed level of
consciousnessa
Hypertoniaa
Coordination
abnormalitya
Miosisa
Ileusa (including
paralytic ileus)
Megacolona
(including toxic
megacolonb)
Glossodyniaa
Abdominal
distension
Bullous eruptiona
(including
Stevens-Johnson
syndrome, toxic
epidermal
necrolysis and
erythema
multiforme)
Angioedemaa
Urticariaa
Pruritusa
Urinary retentiona

System Organ
Class

Indication
Common

Uncommon

General Disorders
and Administration
Site Conditions

Rare
Fatiguea

a: Inclusion of this term is based on post-marketing reports for loperamide
hydrochoride. 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 hydrochoride (acute and
chronic), including trials in children ≤ 12 years (N=3683).
b: See section 4.4 Special Warnings and Special Precautions for use.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisations of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme at: www.mhra/gov.uk/yellowcard
4.9

Overdose
Symptoms
In case of overdose (including relative overdose due to hepatic dysfunction) CNS
depression (stupor, coordination abnormality, somnolence, miosis, muscular
hypertonia and respiratory depression), urinary retention and ileuss may occur.
Children may be more sensitive to CNS effects than adults.
Management
If symptoms of overdose occur, naloxone can 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. Therefore, the patient should
be monitored closely for at least 48 hours in order to detect any possible CNS
depression.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic Group: Antipropulsives;

ATC code: A07DA03
Loperamide hydrochloride is a synthetic opioid which inhibits gut motility by binding
to opiate receptors in the gut wall and may also reduce gastrointestinal secretions,
resulting in improvement in diarrhoea symptoms.
Loperamide also increases the tone of the anal sphincter. Onset of antidiarrhoeal
effect occurred as soon as one hour after intake of a 4 mg dose of loperamide.
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
Loperamide hydrochloride is well absorbed from the gut. 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 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 hydrochloride reaches the systemic
circulation.
The half-life of loperamide hydrochloride in man is about 11 hours with a range of 9 14 hours. Excretion takes place mainly via faeces.

5.3

Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies
of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential,
toxicity to reproduction and development.
Acute and chronic studies on loperamide showed no specific toxicity.
Loperamide had no effect on fertility in male rats when administered orally prior to
mating at doses up to approximately 40 mg/kg. No pregnancy occurred in females
dosed with approximately 40 mg/kg. Lower doses (approximately 10 and 2.5mg/kg)
did not affect female fertility. In rabbits no differences in pregnancy rate were
observed when females were administered orally up to 40mg/kg.

No malformations of offspring were noted in rats and rabbits dosed up to 40 mg/kg.
Loperamide did no show genotoxic potential.
In an 18-month carcinogenicity study in rats, with doses up to 100 times the
maximum human dose no evidence of carcinogenesis was found.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose
Maize Starch
Talc
Magnesium Stearate
Gelatin
Quinoline Yellow
Erythrosine
Patent Blue
Titanium Dioxide

6.2

Incompatibilities
None.

6.3

Shelf life
36 Months.

6.4

Special precautions for storage
This product requires no special storage precautions.

6.5

Nature and contents of container
Blister strips comprising 20 micron printed aluminium foil and 250 micron clear PVC
/ 40gsm PVdC film. The blister strips are enclosed in a printed cardboard carton with
a patient information leaflet.

Pack Sizes of 6, 8, 10, 12 or 20 capsules. Not all pack sizes may be marketed.

6.6

Special precautions for disposal
Medicines should not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer required. These measures will
help to protect the environment.
2B

7.

MARKETING AUTHORISATION HOLDER

Galpharm Healthcare Limited
Wrafton
Braunton
Devon
EX33 2DL
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 16028/0150

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
24/05/2012

10

DATE OF REVISION OF THE TEXT
20/03/2017

Expand Transcript

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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