Hidrasec
Produktinformationen för Hidrasec 100 mg kapsel, hård MTnr 46035, gäller vid det tillfälle då läkemedlet godkändes. Informationen kommer inte att uppdateras eftersom läkemedlet inte marknadsförs i Sverige. Av samma anledning finns inte någon svensk produktinformation.
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SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
TIORFAN 100 mg hard capsule
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 100 mg of racecadotril.
Excipients: Each capsule contains 41 mg lactose monohydrate
For full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
Capsule, hard capsule
Ivory coloured capsules, size 2, containing a white powder with a sulphur odor.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
TIORFAN is indicated for the symptomatic treatment of acute diarrhoea in adults when causal treatment is not possible.
If causal treatment is possible, racecadotril can be administered as a complementary treatment
4.2 Posology and method of administration
For oral use.
Adults:
One capsule initially regardless of the time of day. Then, one capsule three times daily preferably before the main meals. Treatment should be continued until two normal stools are recorded. Treatment should not exceed 7 days.
Special populations:
Children:There are specific formulations intended for infants,children andadolescents.
Elderly: Dosage adjustment is not necessary in the elderly.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
4.4 Special warnings and special precautions for use
Precautions for use:
The administration of racecadotril does not modify the usual rehydration regimens.
The presence of bloody or purulent stools and fever may indicate the presence of invasive bacteria as a reason for diarrhoea, or the presence of other severe disease. Therefore, racecadotril should not be administered under these conditions.
Chronic diarrhoea has not been sufficiently studied with this medicinalproduct. Also, racecadotril has not been tested in antibiotic associated diarrhoea.
There are limited data in patients with renal or hepatic impairment. These patients should be treated with caution (see section 5.2).
There is a possible reduced availability in patients with prolonged vomiting.
Warning:
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
To date, no interactions with other medicinal products have been described in humans.
In humans, concomitant treatment with racecadotril and loperamide or nifuroxazide does not modify the kinetics of racecadotril.
4.6 Fertility, pregnancy and lactation
Fertility:fertility studies conducted with racecadotril on Sprague-Dawley Rats demonstrates no impact on fertility.
Pregnancy:
There are no adequate data from the use of racecadotril in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy,fertility, embryonal/ foetal development, parturition or postnatal development. However, since no specific clinical studies are available, racecadotril should not be administered to pregnant women.
Lactation:
Due to the lack of information regarding racecadotril secretion in human milk, this medicinal product should not be administered to breastfeeding women.
4.7 Effects on the ability to drive and use machines
Racecadotril has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Data from pharmacological and clinical studies are available for 2,714 adult patients treated with racecadotril and 496 treated with placebo. The overall incidence of adverse events was 13.6% in patients treated with racecadotril and 22% in placebo groups. The most frequent were headache (1.8% vs. 1.6%), nausea (1.5% vs. 2.4%), and constipation (1.3% vs. 1.4%).
The following adverse drug reactions listed below have occurred with racecadotril more often than with placebo or have been reported during post-marketing surveillance. The frequency of adverse reactions is defined using 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), not known (cannot be estimated from the available data).
Nervous system disorders
Common: headache.
Skin and subcutaneous tissue disorders
Uncommon: rash, erythema.
Unknown: erythema multiforme, tongue oedema, face oedema, lip oedema, eyelid oedema, angioedema, urticaria, erythema nodosum, rash papular, prurigo, pruritus, toxic skin eruption.
4.9 Overdose
No cases of overdose have been reported.
In adults, single doses above 2 g, which is equivalent to 20 times the therapeutic dose, have been administered, and no harmful effects have been described.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group:Other antidiarrhoeals.
ATC code:A07XA04
Racecadotril is a prodrug that needs to be hydrolysed to its active metabolite thiorphan, which is an inhibitor of enkephalinase, a cell membrane peptidase located in various tissues, notably the epithelium of the small intestine. This enzyme contributes both to the hydrolysis of exogenous peptides and to the breakdown of endogenous peptides such as enkephalins. Consequently, racecadotril protects endogenous enkephalins that are physiologically active at digestive tract level, prolonging their antisecretory effect.
Racecadotril is a pure intestinal antisecretory active substance. It decreases the intestinal hypersecretion of water and electrolytes induced by cholera toxin or inflammation, and does not have effects on basal secretory activity. Racecadotril exerts rapid antidiarrhoeal action, without modifying the duration of intestinal transit.
Racecadotril does not produce abdominal distension. During its clinical development, racecadotril produced secondary constipation at a rate comparable to placebo.
When administered via the oral route, its activity is exclusively peripheral, with no effects on the central nervous system.
5.2 Pharmacokinetic properties
Absorption: following oral administration, racecadotril is rapidly absorbed. The initial time to plasma enkephalinase inhibition is 30 minutes.
The bioavailability of racecadotril is not modified by food, but peak activity is delayed by about one hour and a half.
Distribution: Only about 1% of the dose administered is distributed in tissues. Ninety percent of the active metabolite of racecadotril, (RS)-N-(1-oxo-2-(mercaptomethyl)-3-phenylpropyl) glycine, is bound to plasma proteins, mainly to albumin.
The duration and extent of the effect of racecadotril are dose-dependent. Time to peak plasma enkephalinase inhibition is approximately 2 hours and corresponds to 75% inhibition with the dose of 100 mg.
With a dose of 100 mg, the duration of plasma enkephalinase inhibition is about 8 hours.
Metabolism: The biological half-life of racecadotril, measured as plasma enkephalinase inhibition, is 3 hours approximately.
Racecadotril is rapidly hydrolysed to (RS)-N-(1-oxo-2-(mercaptomethyl)-3-phenylpropyl) glycine, the active metabolite, which is in turn transformed into inactive metabolites. Repeated administration of racecadotril does not cause any accumulation in the body.
Racecadotril does not modify protein binding of active substances strongly bound to proteins, such as tolbutamide, warfarin, niflumic acid, digoxin or phenytoin.
In patients with liver failure [cirrhosis, grade B of the Child-Pugh classification], the kinetic profile of the active metabolite of racecadotril showed similar Tmax and T½ and lesser Cmax (-65%) and AUC (-29%) as compared to healthy subjects.
In patients with severe renal failure (creatinine clearance 11-39 ml/min), the kinetic profile of the active metabolite of racecadotril showed smaller Cmax (-49%) and greater AUC (+16%) and T½ as compared to healthy volunteers (creatinine clearance >70 ml/min).
Excretion:Racecadotril is eliminated as inactive metabolites. Elimination is mainly via the renal route, and to a much lesser extent via the faecal route. The pulmonary route is not significant.
In vitro data indicates that racecadotril/tiorphan does not inhibit the CYP enzymes 3A4, 2D6, 2C9, 1A2 and 2C19 to an extent that would be clinically relevant.
5.3 Preclinical safety data
Chronically (1 year) treated adult monkeys at a dose of 500 mg/kg/d showed generalized infections and reduced antibody responses to vaccination. Racecadotril was not immunotoxic in mice given racecadotril during 1 week or 1 month.
Preclinical effects (e.g., severe, most likely aplastic anaemia, increased diuresis, ketonuria, diarrhoea) were observed only at exposures considered sufficiently in excess of maximum human exposure. Their clinical relevance is unknown.
In animals, racecadotril reinforced the effects of butylhyoscine upon bowel transit and on the anticonvulsive effects of phenytoin.
Racecadotril is not considered to have a clinically relevant genotoxic potential.
The studies in animals have shown no teratogenic effects.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Powder
Lactose monohydrate
Pregelatinised starch (maize)
Magnesium stearate
Colloidal anhydrous silica
Capsule
Yellow iron oxide (E172)
Titanium dioxide (E171)
Gelatine
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
PVC-PVDC/ Aluminium blister.
Packs containing 6, 20, 100 (5 packs x 20 capsules) and 500 capsules.
Not all pack sizes may be marketed.
6.6 Instructions for use and handling
No special requirements.
7. MARKETING AUTHORIZATION HOLDER
(to be completed nationally)
8. MARKETING AUTHORIZATION NUMBER
(to be completed nationally)
9. DATE OF FIRST /RENEWAL OF THE AUTHORIZATION
Date of first authorisation: (to be completed nationally)
Date of first Renewal of the authorisation: June 4, 2007
10. DATE OF REVISION OF THE TEX