Tuesday 26 June 2012

Imodium Instants





1. Name Of The Medicinal Product



Imodium Instants


2. Qualitative And Quantitative Composition



Loperamide hydrochloride 2 mg per tablet.



For excipients see section 6.1.



3. Pharmaceutical Form



Orodispersible tablet.



Imodium Instants are white to off-white, circular, freeze-dried tablets.



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 orodispersible tablet should be placed on the tongue. The tablet will dissolve and is to be swallowed with saliva. No liquid intake is needed for the orodispersible tablet.



Acute diarrhoea:



Adults, the elderly, and children 12 years and over:



Two tablets (4 mg) initially followed by 1 tablet (2 mg) after every loose stool. The maximum daily dose should not exceed 6 tablets (12 mg).



Symptomatic treatment of acute episodes of diarrhoea associated with irritable bowel syndrome



Adults aged 18 years and over:



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



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 Instants 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. Allow the tablet to disintegrate on the tongue and swallow the medication.



4.3 Contraindications



Imodium Instants is contraindicated:



• in patients with a 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 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 Instants 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 Instants must be discontinued promptly when ileus, constipation or abdominal distension develop.



4.4 Special Warnings And Precautions For Use



Treatment of diarrhoea with Imodium Instants 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 Imodium Instants 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 24 hours, the administration of Imodium Instants should be discontinued and patients should be advised to consult their doctor.



Patients with AIDS treated with Imodium Instants 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, Imodium Instants 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.



If you are taking Imodium Instants to control episodes of diarrhoea associated with Irritable Bowel Syndrome previously diagnosed by your doctor, you should return to him/her if the pattern of your symptoms changes. You should also return to your doctor if your episodes of diarrhoea continue for more than two weeks or there is a need for continued treatment of more than two weeks.



Special Warnings to be included on the leaflet:



Only take Imodium Instants 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 40 years or over and it is some time since your last attack of IBS or the 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, 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 (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).



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 Pregnancy And Lactation



Safety in human pregnancy has not been established, although from animal studies there are no indications that loperamide HCl posseses any teratogenic or embryotoxic properties. As with other drugs, it is not advisable to administer loperamide in pregnancy, especially during the first trimester.



Small amounts of loperamide may appear in human breast milk. Therefore loperamide is not recommended during breast-feeding.



Women who are pregnant or breast-feeding 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 loperamide. 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



The safety of loperamide HCl was evaluated in 2755 adults and children aged



The most commonly reported (i.e.



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 (



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 consciousnessa



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)



Glossodyniaa



Abdominal distension




Skin and Subcutaneous Tissue Disorders



 


Rash




Bullous eruptiona (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme)



Angioedemaa



Urticariaa



Pruritusa




Renal and Urinary Disorders



 

 


Urinary retentiona




General Disorders and Administration Site Conditions



 

 


Fatiguea




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



b: See section 4.4 Special Warnings and Special Precautions for use.


   


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 possible CNS depression.



5. Pharmacological Properties



ATC Code: A07DA



5.1 Pharmacodynamic Properties



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 anti-diarrhoeal 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



Not applicable.



6. Pharmaceutical Particulars



6.1 List Of Excipients



Gelatin



Mannitol



Aspartame



Sodium hydrogen carbonate



Mint flavour



6.2 Incompatibilities



Not applicable.



6.3 Shelf Life



36 months.



6.4 Special Precautions For Storage



Store in the original package.



6.5 Nature And Contents Of Container



All-aluminium blister packs of 2, 4, 5 or 6 tablets in printed cardboard cartons. The all-aluminium blisters are made from paper, PET, aluminium, PVC and polyamide.



Not all pack sizes may be marketed.



6.6 Special Precautions For Disposal And Other Handling



Not applicable.



7. Marketing Authorisation Holder



McNeil Products Limited



Foundation Park



Roxborough Way



Maidenhead



Berkshire



SL6 3UG



United Kingdom



8. Marketing Authorisation Number(S)



PL 15513/0345



9. Date Of First Authorisation/Renewal Of The Authorisation



20 May 2002



10. Date Of Revision Of The Text



27 July 2011




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