Diocalm Ultra Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Diocalm Ultra Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Loperamide hydrochloride EP 2.0mg/capsule Also contains lactose.
For full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Capsule
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the symptomatic treatment of acute diarrhoea
4.2 Posology and method of administration Posology
Adults, the elderly and children aged 12 years and over
The initial dose is 2 capsules (4mg), followed by 1 capsule (2mg) after each further bout of diarrhoea, up to a maximum of 6 capsules in any 24 hours.
Not to be given to children under 12 years.
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 HCl should be used with caution in such patients because of reduced first pass metabolism. (see section 4.4 Special warnings and special precautions for use).
Method of administration
Oral. The capsules should be taken with liquid.
4.3 Contraindications
Hypersensitivity to the active ingredient, or to any of the excipients listed in section 6.1.
Conditions where inhibition of peristalsis is to be avoided e.g. constipation, diverticular disease and ulcerative colitis. This is due to the possible risk of significant sequelae including ileus, megacolon and toxic megacolon.
Loperamide HCl should not be used as the primary therapy:
• in patients with acute dysentery, which is characterized 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.
Loperamide HCl must be discontinued promptly when constipation, abdominal distension or ileus develop.
Not to be given to children under 12 years of age.
4.4 Special warnings and precautions for use
Treatment of diarrhoea with loperamide HCl is only symptomatic. Whenever an underlying etiology can be determined, specific treatment should be given when appropriate.
In patients with diarrhoea, fluid and electrolyte depletion may occur. In such cases administration of appropriate fluid and electrolyte replacement therapy is the most important measure.
This product should be used with caution in cases of impaired liver function.
Although no pharmacokinetic data are available in patients with hepatic impairment, loperamide HCl should be used with caution in such patients because of reduced first pass metabolism. This medicine must be used with caution in patients with hepatic impairment as it may result in a relative overdose leading to CNS toxicity.
Patients suffering from irritable bowel syndrome should not use this product. The first line of treatment in acute diarrhoea is the prevention or treatment of fluid and electrolyte depletion; this is of particular importance to frail and elderly patients.
The following will appear on the product labelling:
Warning: Do not exceed the stated dose
Keep out of the sight and reach of children
If symptoms persist for more than 24 hours consult your doctor
If you are pregnant, consult your doctor before use
This medicine is for the relief of the symptoms of diarrhoea and is not a substitute for oral rehydration therapy.
In acute diarrhoea, if clinical improvement is not observed within 48 hours, the administration of loperamide HCl should be discontinued and patients should be advised to consult their physician.
Patients with AIDS treated with loperamide HCl 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 HCl.
Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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, 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). Gemfibrozil also prolonged the half-life of loperamide.
Use with co-trimoxazole increases the bioavailability of loperamide, apparently by inhibiting its first-pass metabolism.
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.
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
Pregnancy
It is not advisable to administer this medicine in pregnancy.
Women who are pregnant should therefore be advised to consult their doctor for appropriate treatment.
Breast-feeding
Loperamide is distributed into breast milk in small amounts. Women who are breastfeeding should be advised to consult their doctor for appropriate treatment.
Fertility
No known effects.
4.7 Effects on ability to drive and use machines
Tiredness, dizziness, or drowsiness may occur in the setting of diarrhoeal syndromes treated with loperamide HCl. Therefore, it is advisable to use caution when driving a car or operating machinery.
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 clinical trial in 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
|
Indication System Organ Class |
Acute Diarrhoea (N=2755) |
Acute + Chronic Diarrhoea and postmarketing experience |
|
Immune System Disorders Hypersensitivity reaction3 , Anaphylactic reaction (including Anaphylactic shock)a, Anaphylactoid reactiona |
Rare | |
|
Nervous System Disorders | ||
|
Headache |
Common |
Common |
|
Dizziness |
Uncommon |
Common |
|
Somnolence3 |
Uncommon | |
|
Loss of consciousness*1, Stupor*1 , Depressed level of consciousness*1 , Hypertonia*1, Coordination abnormality*1 |
Rare | |
|
Eye Disorders Miosis*1 |
Rare | |
|
Gastrointestinal Disorders | ||
|
Constipation, Nausea, Flatulence |
Common |
Common |
|
Abdominal pain, Abdominal discomfort, Dry mouth |
Uncommon |
Uncommon |
|
Abdominal pain upper, Vomiting |
Uncommon |
Uncommon |
|
Dyspepsia |
Uncommon | |
|
Ileus*1 (including paralytic ileus), Megacolona (including toxic megacolonb), |
Rare | |
|
Glossodyniaa | ||
|
Abdominal distension |
Rare |
Rare |
|
Skin and Subcutaneous Tissue Disorders Rash Skin and Subcutaneous Tissue Disorders |
Uncommon |
Uncommon |
|
Bullous eruption*1 (including Stevens-Johnson syndrome, Toxic epidermal necrolysis and Erythema multiforme), Angioedemaa, Urticaria*1 , Pruritus*1 |
Rare | |
|
Renal and Urinary Disorders Urinary retention*1 |
Rare | |
|
General Disorders and Administration Site Conditions | ||
|
Fatigue*1 |
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.
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), urinary retention and ileus may occur. Children may be more sensitive to CNS effects than adults.
The following effects may be observed in cases of overdose:- constipation and neurological symptoms.
Treatment
Treatment would be symptomatic. In severe overdose, 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: Antipropulsives: ATC Code - A07DA03
By binding to opiate receptors in the gut wall, loperamide hydrochloride reduces propulsive peristalsis, increases intestinal transit time and enhances resorption of water and electrolytes.
5.2 Pharmacokinetic properties
Following partial absorption in the gastro-intestinal tract, loperamide undergoes first-pass metabolism in the liver and is excreted predominantly in the faeces. The elimination half-life is reported as about 10 hours.
5.3 Preclinical safety data
Not applicable.
6.1 List of excipients
Lactose (DMV), maize starch (dried), microcrystalline cellulose (Avicel PH101), pregelatinised starch (dried), croscarmellose sodium, dimeticone.
Shell cap: yellow iron oxide (E172), black iron oxide (E172), indigo carmine (E132), titanium dioxide (E171), gelatin.
Shell body: titanium dioxide (E171), gelatin.
6.2 Incompatibilities
None stated.
6.3 Shelf life
36 months unopened.
6.4 Special precautions for storage
None.
6.5 Nature and contents of container
White blisters of hard polyvinylchloride 250pm thick backed with aluminium foil 0.02 hard silver, smooth shiny-sided hot sealable against PVC and PVdC dull sided unprinted. 6 capsules per strip are packed in a cardboard carton.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
SSL International PLC Venus,
1 Old Park Lane,
Trafford Park,
Manchester M41 7HA UK
MARKETING AUTHORISATION NUMBER(S)
PL 17905/0049
9
10
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
31/01/2006
DATE OF REVISION OF THE TEXT
18/02/2016