ALIMIX ® Cisapride monohydrate

ALIMIX ® is a drug based on cisapride monohydrate.

THERAPEUTIC GROUP: spasmolytics, prokinetics.

IndicationsAction mechanismStudies and clinical effectiveness Usage and dosage instructionsWarnings Pregnancy and lactationInteractionsContraindicationsUndesirable effects

Directions ALIMIX ® Cisapride monohydrate

ALIMIX ® is indicated in the treatment of dyspeptic disorders in the absence of organic lesions of the digestive tract, in gastro-oesophageal reflux and in the symptomatic treatment of gastroparesis of various origins.

Mechanism of action ALIMIX ® Cisapride monohydrate

ALIMIX ® through its active ingredient cisapride, is able to enhance the normal release of acetylcholine at the level of the myenteric plexus, and to stimulate the contraction of smooth muscles. More precisely, its molecular action translates - at a functional level - into an increase:

oesophageal peristaltic activity and lower esophageal sphincter tone, with consequent prevention of gastro-oesophageal reflux
of contractility of the stomach, with consequent improvement of gastric emptying and antrol-duodenal coordination
intestinal propulsive activity, with a more rapid intestinal transit.

The cisapride contained in ALIMIX ® is rapidly and totally absorbed following oral administration, reaching maximum plasma peaks around 120 minutes from ingestion. After carrying out its biological action, cisapride is metabolized and subsequently excreted in equal parts through urine and faeces.

Studies carried out and clinical efficacy

1 INEFFECTIVE CISAPRIDE IN THE TREATMENT OF THE ESOPHAGEAL GASTRO REFLUX OF BABIES

This study focuses on the real efficacy of cisapride in the treatment of gastro-oesophageal reflux in newborns. In particular, from the studies carried out with more than 260 recruited subjects, no statistically significant evidences emerge on the efficacy of this active principle in the attenuation of the symptomatology, emphasizing instead the presence of important side effects, such as diarrhea and arrhythmias. In light of these data, the authors suggest the need for close specialist supervision during the treatment period.

2. CISAPRIDE AND GASTRO-ESOPHAGEAL REFLUX

This metanalysis study - which evaluated more than ten years of literature - shows that cisapride is second only to omeprazole in the pharmacological treatment of gastro-oesophageal reflux disease. Despite the effectiveness of cisapride in reducing symptoms, the percentage of relapse (33%) is decidedly higher than that observed for omeprazole (17%), which to date remains the first choice treatment.

3. CISAPRIDE And dyspepsia

A very important study in meta-analysis, which recovers more than 50 years of studies for a total of 1844 patients suffering from functional dyspepsia, shows how the use of prokinetics for the treatment of functional dyspepsia can guarantee a significant improvement in health status, although it is of a chronic condition.

Method of use and dosage

ALIMIX ® 10 mg tablets: we recommend taking one tablet three times a day, possibly 15 minutes before meals

ALIMIX ® oral suspension 10mg / 3g: in children under 25 kg the dosage of 0.2mg / kg should never be exceeded 3-4 times a day

The daily dose should be halved in case of hepatic and renal insufficiency.

Warnings ALIMIX ® Cisapride monohydrate

The use of ALIMIX ® is not recommended in the case of organic damage to the digestive tract, for which the increase in motility could result in a worsening of symptoms.

In addition, for patients with potential risk factors for cardiac arrhythmias, renal insufficiency, respiratory failure and alterations of the normal electrolyte balance, a control electrocardiogram and an assessment of serum levels of some minerals and renal function would be indicated, before administering of ALIMIX ®

Although there are still not enough experimental data, we do not recommend taking ALIMIX ® in patients suffering from pheochromocytoma (a rare form of tumor characterized by an increased secretion of catecholamines) due to the possible onset of hypertensive crises.

Alimix ® alone does not affect attention and perception and does not cause drowsiness; however, if taken in conjunction with barbiturates or alcohol, it could accelerate the absorption time and interfere with the normal functioning of the nervous system.

PREGNANCY AND BREASTFEEDING

Experimental studies in animals and clinical studies conducted on humans have not shown any embryotoxic or teratogenic effects of ALIMIX ®. However, it should be avoided to take them during the first trimester of pregnancy.

Pharmacokinetic studies of the drug have highlighted the presence of a small proportion of Cisapride in breast milk; therefore it is advisable to stop breast-feeding during treatment with ALIMIX ®

Interactions ALIMIX ® Cisapride monohydrate

Given the prokinetic capabilities of the ALIMIX ® the normal absorption profile of various drugs could be altered; more precisely gastric absorption (due to increased motility) and accelerated intestinal absorption could be reduced. Consequently. ALIMIX ® can interact with:

Benzodiazepines, alcohol and anxiolytics, accelerating their effects;
Azole antifungals, macrolide antibiotics (erythromycin, clarithromycin and troleandomycin), inhibitors of HIV and nefazodone proteases, can inhibit the enzyme CYP3A4, responsible for cisapride metabolism, inducing an increase in plasma levels of the drug with consequent increased risk of cardiac arrhythmias and Tachycardia.
Antiarrhythmics, tricyclic antidepressants, tetracyclic antidepressants, antipsychotics, antihistamines, bepidril, halofantrine and sparfloxacine, which - by lengthening the QT interval - may subject the patient to risk of cardiovascular events.
Grapefruit juice and cimetidine, which increase its bioavailability .

Contraindications ALIMIX ® Cisapride monohydrate

ALIMIX ® is contraindicated in case of hypersensitivity to the active ingredient or to one of its components, in patients with QT interval lengthening or undergoing therapy with drugs able to lengthen this interval, in hypokalemia or hypomagnesemia conditions, in premature newborns for the first three months of life, in patients with hepatic and renal insufficiency, for which it is possible to halve the dose only under strict medical supervision.

ALIMIX ® contains aspartame; therefore against indicated in patients with phenylketonuria.

Undesirable effects ALIMIX ® Cisapride monohydrate

Given the biological effect of ALIMIX ® it is possible to find with a certain frequency:

diarrhea
abdominal cramps
bowel sounds.

On the other hand, episodes of hypersensitivity to cisapride or to one of its metabolites are less frequent, characterized by skin rash, pruritus, urticaria, headache and bronchospasm.

Reports made regarding CNS side effects, such as compulsive symptoms, alterations in the hematological picture were not directly correlated to the intake of ALIMIX ®

Instead, it was possible to find tachycardia and arrhythmia events in patients undergoing drug therapy with CYP3A4 enzyme inhibitors or those suffering from heart disease or risk factors for pre-existing arrhythmias.

Excessive doses of ALIMIX ® can cause lengthening of the QT interval, diarrhea and abdominal cramps, while in children they can produce sedative effects, apathy and atony.