Loperamide 2mg Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Loperamide 2mg Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Loperamide Hydrochloride 2mg
3 PHARMACEUTICAL FORM
Capsules, hard
Green and grey hard capsules marked with ‘Max’ on the green cap and ‘Lop’ on the grey body.
For a full list of excipients, see section 6.1.
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 (IBS) in adults aged 18 years and over following initial diagnosis by a doctor.
4.2 Posology and method of administration
The capsules should be taken with liquid. For oral administration.
a) Acute diarrhoea
Adults and children over 12 years of age
Two capsules (4mg) initially followed by 1 capsule (2mg) after every loose stool (motion). The usual dose is 3-4 capsules (6mg - 8mg) a day. The total daily dose should not exceed 6 capsules (12mg).
b) 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 ever loose stool (motion), 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, Loperamide Hydrochloride should be used with caution in such patients because of reduced first pass metabolism. (see 4.4 Special warnings and special precautions for use).
4.3 Contraindications
This medicine is contraindicated:
• In patients with known hypersensitivity to Loperamide hydrochloride or to any of the excipients.
• In children less than 12 years of age.
• In patients with acute dysentery, which is characterised by blood in the 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.
Loperamide Hydrochloride must not be used when inhibition of peristalsis is to be avoided due to possible risk of significant sequelae including ileus, megacolon and toxic megacolon. Loperamide Hydrochloride must be discontinued promptly when ileus, constipation or abdominal distension develop.
4.4 Special warnings and precautions for use
Treatment of diarrhoea with Loperamide Hydrochloride is only symptomatic. Whenever an underlying aetiology 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 Loperamide Hydrochloride should be discontinued and patients should be 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.
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.
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 Hydrochloride 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 this medicine to treat acute episodes of diarrhoea associated with Irritable Bowel Syndrome (IBS) 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 has been 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 of lose 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 symptoms worsen, or if your symptoms have not improved over two weeks.
Keep all medicines out of the sight and reach of children.
Ponceau 4R (E124) can cause allergic-type reactions including asthma. Allergy is more common in those people who are allergic to aspirin.
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 intraconazole and gemfibrozil resulted in a 4-fold increase in the peak levels of Loperamide and a 13-fold increase in the 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 Pregnancy and lactation
Safety in human pregnancy has not been established, although from animal studies there are no indications that Loperamide Hydrochloride possesses 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 of 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 and drowsiness may occur. Patients should be advised that if affected they should not drive, operate machinery or take part in activities where such symptoms could put themselves or others at risk.
See section 4.8, Undesirable effects.
4.8 Undesirable effects
Adults and children aged 12 years and over.
The safety of Loperamide hydrochloride was evaluated in 2755 adults and children aged 12 years and over who participated in 26 controlled and uncontrolled clinical trials of Loperamide hydrochloride used for the treatment of acute diarrhoea.
The most commonly reported (i.e. > 1% incidence) Adverse Drug Reactions (ADRs) in clinical trials with Loperamide Hydrochloride 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 Hydrochloride 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); Very Rare ( 1/10,000).
Table 1: Adverse Drug Reactions_
|
System Organ Class |
Indication | ||
|
Common |
Uncommon |
Rare | |
|
Immune System Disorders |
Hypersensitivity reactiona Anaphylactic reaction (including anaphylactic shock)a Anaphylactoid reactiona | ||
|
Nervous System Disorders |
Headache |
Dizziness Somnolencea |
Loss of consciousness Stupora Depressed level of consciousnessa Hypertoniaa Coordination abnormalitya |
|
Eye Disorders |
Miosisa | ||
|
Gastrointestinal Disorders |
Constipation Nausea Flatulence |
Abdominal Pain Abdominal Discomfort Dry Mouth Abdominal pain upper Vomiting Dyspepsiaa |
Ileusa (including paralytic ileus) Megacolona (including toxic megacolonb) Abdominal distension. |
|
Skin & Subcutaneous Tissue Disorders |
Rash |
Bullous eruptiona (including Stevens-Johnson syndrome, Toxic | |
|
epidermal necrolysis & Erythema multiforme) Angloedemaa Urticariaa Pruritusa | |||
|
Renal & Urinary Disorders |
Urinary retentiona | ||
|
General Disorders & Administration Site Conditions |
Fatiguea | ||
|
a: Inclusion of this term is based on post-marketing reports for Loperamide Hydrochloride. 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 Hydrochloride (acute & chronic), including trials in children aged 12 years or less (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 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
Large doses of loperamide may cause features of opioid poisoning. The following patients should be referred for medical assessment:
• All patients who have taken a deliberate overdose.
• All children
• Symptomatic adults
• Adults who have ingested 0.4mg/kg of Loperamide or more
Adults who have accidentally ingested less than 0.4mg/Kg and who have no new symptoms since the time of ingestion should be advised to seek medical attention if symptoms develop.
The effects of overdose will be potentiated by concurrent ingestion of alcohol and/or other centrally active drugs.
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. If untreated deep coma and respiratory arrest can occur. Children, and patients with hepatic dysfunction, may be more sensitive to CNS effects.
Pin point pupils are often present but are not a reliable clinical sign. Their absence does not exclude opiate toxicity.
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 possible CNS depression.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antidiarrhoeals, Intestinal Anti-inflammatory/ Antiinfective Agents - 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.
In a double blind randomised trial in 213 patients with acute diarrhoea, loperamide (56 patients) was compared with two other common antidiarrhoeal agents and placebo. Onset of antidiarrhoeal effect occurred as soon as one hour after intake of a 4mg dose of loperamide.
5.2 Pharmacokinetic properties
More than 65% of a dose of loperamide is reported to be absorbed from the gastrointestinal tract. The drug undergoes considerable first pass metabolism in the liver and excretion via the bile in the faeces as the inactive conjugate. As a result of the drug’s high affinity for the gut wall and its high first pass metabolism very little loperamide reached the systemic circulation and therefore there is only a small amount of urinary excretion. The elimination half life is reported to be about 10 hours.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Capsule contents
Lactose monohydrate Magnesium stearate Starch, pregelatinised Capsule shell Gelatin
Ponceau 4R E124 Indigo carmine E132 Titanium dioxide E171 Yellow iron oxide E172 Black iron oxide E172 Printing Ink Black iron oxide E172 Shellac
Propylene glycol
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
36 months
6.4 Special precautions for storage
Do not store above 30°C. Store in the original package.
6.5 Nature and contents of container
Blisters of 250pm PVC/ 40gsm PVdC/ 20pm Aluminium foil. Pack sizes of 2, 4, 6, 8, 10, 12, 14, 16, 18 capsules.
Blisters of 250pm PVC/ 20pm Aluminium foil. Pack sizes of 2, 4, 6, 8, 10, 12, 14, 16, 18 capsules.
Blisters of 250pm PVC/ 40gsm PVdC/ 25 pm Aluminium foil. Pack sizes of 2, 4, 6, 8, 10, 12, 14, 16, 18 capsules.
Blisters of 250pm PVC/ 25 pm Aluminium foil. Pack sizes of 2, 4, 6, 8, 10, 12, 14, 16, 18 capsules.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Max Remedies Ltd William Nadin Way Swadlincote Derbyshire DE11 0BB
8 MARKETING AUTHORISATION NUMBER(S)
PL 31308/0002
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
13/10/2008
10 DATE OF REVISION OF THE TEXT
14/07/2015