DISSENTEN 15CPR 2MG

DISSENTEN 2 MG COMPRESENT

active ingredients

Each tablet contains: Active ingredient: Loperamide Hydrochloride 2 mg. For the full list of excipients, see paragraph 6.1.

Excellent

Magnesium stearate; microgranular cellulose.

Therapeutic indications

Dissenten is indicated for the symptomatic treatment of acute diarrhea and chronic diarrhea.

Contraindications

Hypersensitivity to the active ingredient or any of the excipients. DISSENTEN is contraindicated in children under 6 years. DISSENTEN should not be used as primary therapy: • in patients with acute dysentery, characterized by blood in the feces and high fever; • in patients with acute ulcerative colitis; • in patients with pseudomembranous colitis associated with the use of broad spectrum antibiotics; • in patients with bacterial enterocolitis caused by invasive organisms including Salmonella, Shigella and Campilobacter. In general, the use of DISSENTEN is contraindicated in all cases where an inhibition of peristalsis must be avoided due to the possible risk of significant consequences such as ileo, megacolon and toxic megacolon. If constipation, abdominal distension or ileo immediately cease treatment.

Population

The tablets should be taken with a little liquid. Adults and children aged between 6 and 17 The initial dose is 2 tablets (4 mg) for adults and 1 tablet (2 mg) for children; 1 tablet (2 mg) after each subsequent evacuation of unformed feces (molli). The maximum daily dose for adults is 8 tablets (16 mg). For children the dose should be related to body weight (3 tablets/20 Kg) but should not exceed a maximum of 8 tablets per day. Decrease the dose to the normalization of the feces and stop the treatment in case of stips. Caution: do not use for more than two days. Children under 6 years of age Dissenten should not be used in children under 6 years of age. Seniors In the elderly, dose adjustment is not necessary. Year In patients with kidney damage it is not necessary to adjust the dose. Epathetic Comprogation Although there is no pharmacokinetic data available in patients with liver impairment, DISSENTEN should be used with caution in these patients due to reduced first-pass metabolism (see paragraph 4.4 “Special warnings and precautions of use“).

Conservation

This medicine does not require any special precaution for conservation.

Warnings

The treatment of diarrhea with loperamide hydrochloride is only symptomatic. Whenever a basic etiology can be determined, specific treatment should be given when appropriate. In patients with diarrhea, especially in children, depletion of liquids and electrolytes may occur. In these cases, the most important countermeasure is the administration of adequate replacement therapy based on liquids and electrolytes. It is appropriate to suspend treatment with DISSENTEN if there is no improvement in clinical symptomatology over the next 48 hours at the beginning of therapy, and the patient should consult his physician. Patients with AIDS treated with DISSENTEN to diarrhea, they must suspend therapy to the first signs of abdominal distension. In these patients with infectious colitis of bacterial or viral origin, treated with loperamide hydrochloride, there were isolated cases of stipsis with an increase in the risk of toxic megacolons. Loperamide Hydrochloride is subject to an intense metabolism of first step. Although no pharmacokinetic data is available on patients with liver impairment, loperamide hydrochloride should be used with caution in these patients due to reduced first-pass metabolism. Therefore patients with liver impairment should be carefully monitored in order to highlight possible signs of toxicity to the central nervous system (SNC). In association with overdose, heart events were reported including the extension of the QT range and the QRS complex, point torsion. Some cases were fatal (see paragraph 4.9). Overdose can make the presence of Brugada syndrome manifest. Patients should not exceed the recommended dose and/or do not protract the recommended duration of therapy.

Interactions

Non-clinical data have shown that loperamide is a substrate of P-glycoprotein. Concurrent administration of loperamide (in a single dose of 16 mg) with chinidine or ritonavir, both P-glycoprotein inhibitors, showed an increase of 2 to 3 times of plasma levels of loperamide. The clinical relevance of this drug interaction with P-glycoprotein inhibitors, when loperamide is administered to recommended dosages, is not known. Concurrent administration of loperamide (in a single dose of 4 mg) and itraconazole, a inhibitor of CYP3A4 and P-glycoprotein, showed an increase of 3 to 4 times of plasma concentrations of loperamide. In the same study the gemfibrozil, a CYP2C8 inhibitor, increased the plasma concentrations of loperamide by about 2 times. The combination of itraconazole and gemfibrozil showed a 4-time increase in plasma levels of loperamide peak and an increase of 13 times of total plasma exposure. These increases were not associated with effects on the central nervous system (SNC), as detected by psychomotor tests (e.g. subjective drowsiness and the test of substitution of symbols and digits - Digit Symbol Substitution Test). Concurrent administration of loperamide (in a single dose of 16 mg) and ketoconazole, a inhibitor of CYP3A4 and P-glycoprotein, has resulted in a 5-fold increase in plasma concentrations of loperamide. This increase was not associated with an increase in pharmacodynamic effects, as detected by the pupillometry. Concurrent treatment with oral desmopressin resulted in an increase of 3 times of plasma concentrations of desmopressin, presumably due to a slowdown in gastrointestinal motility. Treatment with substances with similar pharmacological properties can enhance the effect of loperamide and drugs that accelerate intestinal transit can decrease its effect. We do not recommend the concomitant use of cytochrome inhibitors CYP 450.

Effects

Adults and children aged ≥12 years The safety of loperamide hydrochloride was assessed in 3076 adults and children aged ≥12 years who participated in 31 controlled and uncontrolled clinical trials with loperamide hydrochloride used for treating diarrhea. Of these, 26 studies were on acute diarrhea (N=2755) and 5 on chronic diarrhea (N=321). The adverse reactions to the drug (ADR) most commonly reported (i.e. with an incidence ≥1%) during clinical studies with loperamide hydrochloride for the treatment of acute diarrhea were: stipsi (2.7%), flatulence (1.7%), headache (1.2%) and nausea (1.1%). In clinical studies for the treatment of chronic diarrhea, the ADR reported most commonly (i.e. with an incidence ≥1%) were: flatulence (2.8%), stipsi (2.2%), nausea (1.2%) and dizziness (1.2%). Table 1 shows the results of 3076 adult subjects and children aged ≥12 years who took part in 31 controlled and uncontrolled clinical trials with loperamide hydrochloride used for treating diarrhea. Of these, in 26 studies it was acute diarrhea (N=2755) and in 5 chronic diarrhea (N=321). The frequency categories presented in Table 1 use the following convention: very common (≥1/10), common (≥1/100, Table 1 Frequency of adverse reactions reported with the use of loperamide hydrochloride from clinical studies in adults and children aged ≥12 years

Loperamide Hydrochloride, Post-marketing adverse reactions data Since the process of determining the post-marketing aDR of loperamide hydrochloride did not differentiate between indications of chronic and acute diarrhea or between adults and children, the adverse reactions listed below represent the combined indications and the subject populations. The adverse reactions identified in the post-marketing period for loperamide hydrochloride are listed through the Classification for systems and organs and the Medical Dictionary for Regulatory Activities (MeDRA) according to the Preferred Terms (PT): Immune system disorders: reaction of hypersensitivity, anaphylactic reaction (including anaphylactic shock), anaphylactic reaction. Diseases of the nervous system: drowsiness, loss of consciousness, astonishment, depression of levels of consciousness, hypertonia, abnormal coordination. Eye pathologies: myosis. Gastrointestinal diseases: ileo (including paralytical ileo), megacolon (including toxic megacolon), glossodinia, acute pancreatis (non-known frequency). Pathologies of skin and subcutaneous tissue: bollous eruption syndrome (including Stevens-Johnson syndrome, toxic epidermal necrolysis and multiform erythema), angioedema, hives, itching. Kidney and urinary pathologies: urinary retention. Systemic pathologies and conditions for administration: fatigue. Pediatric population The safety of loperamide hydrochloride has been assessed on 607 patients aged 10 days and 13 years who participated in 13 controlled and uncontrolled clinical trials with loperamide hydrochloride used for treating acute diarrhea. In general, the ADR profile in this patient population was similar to that observed in clinical studies with loperamide hydrochloride in adults and children aged 12 or over. Reporting of suspicious adverse reactions. The reporting of suspicious adverse reactions that occur after the authorization of the medicinal product is important, as it allows continuous monitoring of the benefit/risk ratio of the medicinal product. Healthcare workers are required to report any suspected adverse reaction via the national reporting system at the address www.aifa.gov.it/content/segnalazioni-reazioni-avverse

Overdosing

Synonyms In case of overdose, including that caused by hepatic dysfunction, SNC depression may occur (stepper, coordination abnormalities, drowsiness, myosis, muscle hypertonia, respiratory depression), urinary retention and ileum. In subjects with excessive doses of loperamide, cardiac events such as the extension of the QT range and that of the QRS complex, point torsion, other severe ventricular arrhythmias, cardiac arrest and syncope (see paragraph 4.4) were observed. Fatal cases have also been reported. Overdose can make the presence of Brugada syndrome manifest. Children can be more sensitive than adults to the effects of overdose from loperamide. Therefore it is recommended to keep the product out of their reach because an accidental ingestion, especially in children under 4 years can cause stipsis and depression of the central nervous system with drowsiness and slowing breathing. In this case the child must be kept under careful observation for 48 hours. Treatment Measures in case of overdose: gastric lavender, vomiting, clisma or laxative administration. If overdose symptoms arise, naloxone can be administered as an antidote. Since the duration of loperamide action is more extensive than that of naloxone (from 1 to 3 hours), repeated treatment with naloxone may be indicated. Therefore the patient must be carefully monitored for at least 48 hours to highlight a possible aggravation of the depression of the central nervous system.

Although there are no indications that loperamide hydrochloride possesses teratogenic or embryotoxic properties, the expected therapeutic benefits should be assessed compared to the potential risks before administering loperamide hydrochloride during pregnancy, especially during the first trimester. Small amounts of loperamide can appear in human breast milk. Therefore loperamide hydrochloride is not recommended during lactation.

Source: Farmadati