Imodium Ibs Relief 2 Mg Capsules Soft

Document: spc-doc_PL 15513-0369 change

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Imodium 2 mg Soft Capsules Imodium IBS Relief 2 mg Capsules, soft

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 2 mg Loperamide hydrochloride.

Each capsule also contains 0.06 micrograms of soya lecithin.

For a full list of excipients, see Section 6.1.

3 PHARMACEUTICAL FORM

Capsule, soft (soft capsule)

A clear blue oval soft gelatin capsule.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

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

For the symptomatic treatment of acute episodes of diarrhoea associated with Irritable Bowel Syndrome in adults aged 18 years and over following initial diagnosis by a doctor.

4.2 Posology and method of administration

The capsules should be swallowed whole with water.

ACUTE DIARRHOEA

Adults and children aged 12 years and over:

2 capsules (4mg) initially followed by 1 capsule (2mg) after every loose stool.

The maximum daily dose should not exceed 6 capsules (12mg).

SYMPTOMATIC TREATMENT OF ACUTE EPISODES OF DIARRHOEA ASSOCIATED WITH IRRITABLE BOWEL SYNDROME IN ADULTS AGED 18 YEARS AND OVER

Two capsules (4mg) to be taken initially, followed by 1 capsule (2mg) after every loose stool, or as previously advised by your doctor. The maximum daily dose should not exceed 6 capsules (12mg).

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, Imodium should be used with caution in such patients because of reduced first pass metabolism. (See 4.4 Special warnings and special precautions for use).

Method of administration Oral use.

4.3 Contraindications

This medicine is contraindicated:

• in patients with a known hypersensitivity to loperamide hydrochloride or to any of the excipients.

• in patients with a soya or peanut allergy, as this product contains soya lecithin.

• in children less than 12 years of age.

• in patients with acute dysentery, which is characterised by blood in stools and high fever.

• 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.

Imodium must not be used when inhibition of peristalsis is to be avoided due

to the possible risk of significant sequelae including ileus, megacolon and

toxic megacolon. Imodium must be discontinued promptly when ileus,

constipation or abdominal distension develop.

4.4 Special warnings and precautions for use

Treatment of diarrhoea with Imodium 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 this medicine does not preclude the administration of appropriate fluid and electrolyte replacement therapy.

Since persistent diarrhoea can be an indicator of potentially more serious conditions, this medicine should not be used for prolonged periods until the underlying cause of the diarrhoea has been investigated.

In acute diarrhoea, if clinical improvement is not observed within 48 hours, the administration of Imodium should be discontinued and patients advised to consult their doctor.

Patients with AIDS treated with this medicine 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.

Although no pharmacokinetic data are available in patients with hepatic impairment, this medicine should be used with caution in such patients because of reduced first pass metabolism, as it may result in a relative overdose leading to CNS toxicity.

Dietary soya-products are known to cause allergic reactions including severe anaphylaxis in persons with soya allergy. Patients with known allergy to peanut protein carry out an enhanced risk for severe reactions to soya preparations.

If patients are taking this medicine to control episodes of diarrhoea associated with Irritable Bowel Syndrome previously diagnosed by their doctor, and clinical improvement is not observed within 48 hours, the administration of loperamide HCl should be discontinued and they should consult their doctor. Patients should also return to their doctor if the pattern of their symptoms changes or if the repeated episodes of diarrhoea continue for more than two weeks.

Special Warnings to be included on the leaflet:

Only take Imodium to treat acute episodes of diarrhoea associated with Irritable Bowel Syndrome if your doctor has previously diagnosed IBS.

If any of the following now apply, do not use the product without first consulting your doctor, even if you know you have IBS:

• If you are aged 40 or over and it is some time since your last IBS attack.

• If you are aged 40 or over and your IBS symptoms are different this time.

• If you have recently passed blood from the bowel.

• If you suffer from severe constipation.

• If you are feeling sick or vomiting.

• If you have lost your appetite or lost weight.

• If you have difficulty or pain passing urine.

• If you have a fever.

• If you have recently travelled abroad.

Consult your doctor if you develop new symptoms, or if your symptoms worsen, or your symptoms have not improved over two weeks.

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 (16mg 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 is unknown.

The concomitant administration of loperamide (4mg 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 (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.

Concomitant treatment with oral desmopressin resulted in a 3-fold increase of desmopressin plasma concentrations, presumably due to slower gastrointestinal motility.

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 from animal studies there are no indications that loperamide HCl possesses any teratogenic or embryotoxic properties. As with other drugs, it is not advisable to administer this medicine in pregnancy, especially during the first trimester.

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.

4.7 Effects on ability to drive and use machines

Loss of consciousness, depressed level of consciousness, tiredness, dizziness, or drowsiness may occur when diarrhoea is treated with this medicine. 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 2755 adults and children aged > 12 years who participated in 26 controlled and uncontrolled clinical trials of loperamide HCl used for the treatment of acute diarrhoea.

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%).

Table 1 displays ADRs that have been reported with the use of loperamide HCl 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
System Organ Class	Common	Uncommon	Rare
Immune System Disorders			Hypersensitivity reaction^a Anaphylactic reaction (including Anaphylactic shock)^aAnaphylactoid reaction^a
Nervous System Disorders	Headache	Dizziness Somnolence³	Loss of consciousness^a Stupor^a Depressed level of consciousness*¹ Hypertonia^a Coordination abnormality^a
Eye Disorders			Miosis*¹
Gastrointestinal Disorders	Constipation Nausea Flatulence	Abdominal pain Abdominal discomfort Dry mouth Abdominal pain upper Vomiting Dyspepsia^a	Ileus*¹ (including paralytic ileus) Megacolon^a(including toxic megacolon^b) Abdominal distension
Skin and		Rash	Bullous eruption*¹

System Organ Class	Indication
System Organ Class	Common	Uncommon	Rare
Subcutaneous Tissue Disorders			(including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme) Angioedema^a Urticaria^a Pruritus³
Renal and Urinary Disorders			Urinary retention*¹
General Disorders and Administration Site Conditions			Fatigue^a

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 (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 authorisation 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), constipation, urinary retention and ileus may occur. Children and patients with hepatic dysfunction may be more sensitive to CNS effects.

Treatment:

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.

5.1 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

Capsule fill

Propylene glycol monocaprylate Propylene glycol Purified water

Capsule shell Gelatin Glycerol 99%

Propylene glycol Brilliant blue (E133)

Soya lecithin

Triglycerides, medium chain Purified Water

6.2 Incompatibilities

Not applicable

6.3 Shelf life

24 months

6.4 Special precautions for storage

Do not store above 25°C.

Store in the original package to protect from moisture. Keep blister in the outer carton to protect from light.

6.5 Nature and contents of container

PVC/PVDC aluminium blister packed in cardboard cartons containing 12 soft capsules.

6.6 Special precautions for disposal

Any unused product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

McNeil Products Ltd.

Foundation Park Roxborough Way Maidenhead Berkshire SL6 3UG UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 15513/0369

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

04/09/2012

10 DATE OF REVISION OF THE TEXT

17/09/2014