SPA

Dissenten 2mg

Tablets

Composition :

Each tablet contains: Active substance: Loperamide hydrochloride 2 mg For a full list of excipients, see section 6.1.

Excipients

Magnesium stearate; microgranular cellulose.

Therapeutic indications

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

Contraindications

Hypersensitivity to the active substance or to any of the excipients. DISSENTEN is contraindicated in children under 6 years of age. DISSENTEN should not be used as primary therapy: • in patients with acute dysentery, characterized by bloody stools 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 inhibition of peristalsis must be avoided due to the possible risk of significant consequences such as ileus, megacolon and toxic megacolon. If constipation, abdominal distension or ileus occurs, stop treatment immediately.

Dosage

The tablets should be taken with a little liquid. Adults and children 6 to 17 years of age The starting dose is 2 tablets (4 mg) for adults and 1 tablet (2 mg) for children; thereafter 1 tablet (2 mg) after each subsequent evacuation of unformed (soft) faeces. 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 when the stool is normalized and stop treatment in case of constipation. Warning: 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. Elderly No dose adjustment is required in the elderly. Renal impairment No dose adjustment is required in patients with renal impairment. Hepatic impairment Although no pharmacokinetic data are available in patients with hepatic impairment, DISSENTEN should be used with caution in these patients due to impaired first pass metabolism (see section 4.4 "Special warnings and precautions for use").

Warnings and Precautions

Treatment of diarrhea with loperamide hydrochloride is symptomatic only. Whenever an underlying etiology can be determined, specific treatment should be given when appropriate. Fluid and electrolyte depletion may occur in patients with diarrhea, especially children. In these cases, the most important countermeasure is the administration of adequate fluid and electrolyte replacement therapy. Treatment with DISSENTEN should be discontinued if there is no improvement in clinical symptoms within 48 hours after initiation of therapy and the patient should consult their physician. AIDS patients treated with DISSENTEN for diarrhea should discontinue therapy at the first signs of abdominal distension. In these patients with infectious colitis of bacterial or viral origin, treated with loperamide hydrochloride, there have been isolated cases of constipation with an increased risk of toxic megacolon. Loperamide hydrochloride is subject to an intense first pass metabolism. Although no pharmacokinetic data are available in patients with hepatic impairment, loperamide hydrochloride should be used with caution in these patients due to impaired first pass metabolism. Therefore, patients with hepatic impairment should be carefully monitored for signs of central nervous system (CNS) toxicity.

Interactions

Non-clinical data have shown that loperamide is a substrate of P-glycoprotein. Concomitant administration of loperamide (single 16 mg dose) with quinidine or ritonavir, both P-glycoprotein inhibitors, resulted in a 2 to 3-fold increase in plasma loperamide levels. The clinical relevance of this pharmacokinetic interaction with P-glycoprotein inhibitors when loperamide is administered at recommended doses is unknown. Concomitant administration of loperamide (single 4 mg dose) and itraconazole, an inhibitor of CYP3A4 and P-glycoprotein, resulted in a 3 to 4-fold increase in plasma concentrations of loperamide. In the same study, gemfibrozil, a CYP2C8 inhibitor, increased plasma concentrations of loperamide approximately 2-fold. The combination of itraconazole and gemfibrozil showed 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 detected by psychomotor tests (e.g. subjective sleepiness and the Digit Symbol Substitution Test). Concomitant administration of loperamide (single 16 mg dose) and ketoconazole, an inhibitor of CYP3A4 and P-glycoprotein, 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 pupillometry. Concomitant treatment with oral desmopressin resulted in a 3-fold increase in plasma concentrations of desmopressin, presumably due to a slowing of gastrointestinal motility. Treatment with substances with similar pharmacological properties can enhance the effect of loperamide and drugs that accelerate intestinal transit can decrease their effect. Concomitant use of CYP 450 inhibitors is not recommended.

Side effects

Adults and children aged ≥12 years The safety of loperamide hydrochloride was evaluated in 3076 adults and children aged ≥12 years who participated in 31 controlled and uncontrolled clinical trials with loperamide hydrochloride used for the treatment of diarrhea. Of these, 26 studies were on acute diarrhea (N = 2755) and 5 on chronic diarrhea (N = 321). The most commonly reported adverse drug reactions (ADRs) (i.e. with an incidence ≥1%) in clinical trials with loperamide hydrochloride for the treatment of acute diarrhea were: constipation (2.7%), flatulence ( 1.7%), headache (1.2%) and nausea (1.1%). In clinical trials for the treatment of chronic diarrhea the most commonly reported ADRs (i.e. with an incidence ≥1%) were: flatulence (2.8%), constipation (2.2%), nausea (1.2 %) and dizziness (1.2%). Table 1 lists the ADRs that have been reported following the use of loperamide hydrochloride both in clinical trials (in acute or chronic diarrhea or both) and in post-marketing experience. Conventionally, the frequency of undesirable effects is divided into the following categories: very common (≥1 / 10), common (≥1 / 100 to <1/10), uncommon (≥1 / 1000 to <1/100), rare (≥1 / 10,000, <1/1000) and very rare (<1 / 10,000). Table 1 Adverse drug reactions

Pregnancy and breastfeeding

Although there are no indications that loperamide hydrochloride possesses teratogenic or embryotoxic properties, the anticipated therapeutic benefits must be weighed against 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 breastfeeding.

Format

15 tablets