Cisapride adverse effects

II.b.2.1. Prokinetic agents. Cisapride cisapride treatment can be demonstrated to improve sphincter and motor function and to improve modestly the symptoms of heartburn. However, it is relatively ineffective in severe disease, and adverse effects of impaired intracardiac electrical conduction causing ventricular tachyarrhythmias have resulted in its withdrawal from general use. 

Adverse effects of cisapride in causing cardiac dysrhythmias have led to withdrawal from general use. Metoclopramide and domperidone are well described as occasionally causing dyskinesias, particularly in younger people. Treatment is generally licensed for short term typically six week prescription. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Concomitant therapy with astemizole, cisapride, pimozide, or terfenadine Hypersensitivity to erythromycin or any component of the product Adverse effects ... 

GRAPEFRUIT JUICE CISAPRIDE T plasma concentrations and likely T risk of adverse effects (e.g. cardiotoxicity, Q-T prolongation, torsade de pointes) t oral bioavailability and slight but significant t elimination half-life Although a study in volunteers did not show any changes in heart rate, PR or Q-T prolongation, avoid concurrent use... 

A comparison of data from prescription event monitoring in over 13 000 recipients of cisapride and from a further 9726 recipients involved in a controlled study showed that diarrhea, in about 2-4% of patients, was the commonest adverse effect reported. Other relatively common adverse effects are headache, abdominal pain, nausea and vomiting, and constipation, all in about 1-1.5% of patients. 

Before its withdrawal in the UK cisapride was specifically contraindicated in premature babies for up to 3 months after birth, because of the risk of QT interval prolongation (10). Between 1988 and 2000 the Medicines Control Agency received 64 reports of suspected adverse effects of cisapride in children under 13 years, of which two were cases of QT prolongation and two were sudden unexplained deaths. Another 106 cardiovascular events were reported from other countries, including 30 cases of QT prolongation, six cases of ventricular fibrillation or tachycardia, and four sudden unexplained deaths. 

The effect of cisapride 10 mg bd on gastroduodenal reflux and gaU bladder motihty has been assessed in 77 patients with gallstones in a double-blind, placebo-controUed study (20). Cisapride increased gallbladder motility but did not have any effect on gastroduodenal reflux. Diarrhea, abdominal cramps, and increased bladder frequency were common adverse effects. 

A multicenter trial in 353 patients assessed the efficacy and tolerance of sodium alginate (four 10 ml sachets a day) compared with cisapride (5 mg qds) in the symptomatic treatment of uncomplicated gastro-esophageal reflux without severe esophagitis (21). Sodium alginate, which costs less than cisapride, was more effective in relieving symptoms. Adverse effects were rare and not serious. Constipation was the most common adverse effect of alginate while diarrhea was the commonest adverse effect of cisapride. 

The use of cisapride and its benefit to harm balance in children has been reviewed (25). Overall it is well tolerated. The most common adverse effects are diarrhea, abdominal cramps, borborygmi, and colic. Serious adverse events are rare and include isolated cases of extrapyramidal reactions, seizures in epileptic patients, cholestasis, QT interval prolongation and ventricular dysrhythmias, anorexia, and enuresis. Interactions of cisapride with other drugs are similar to those reported in adults. Co-administration of drugs that inhibit CYP3A4, such as imidazoles, macrolide antibiotics, the antidepressant nefazodone, and protease inhibitors such as ritonavir, are contraindicated. Furthermore, co-administration of anticholinergic drugs can compromise the beneficial effects of cisapride. 

The effects of cisapride 0.2-0.3 mg/kg tds on chronic constipation were stndied in a double-blind, placebo-con-trolled trial in 36 children (28). Cisapride was effective in the treatment of chronic constipation without major adverse effects. 

The pharmacokinetics of cisapride have been studied in eight elderly patients (mean age 85 years) (27). There were no adverse effects, apart from a slight increase in stool freqnency. There were no changes in the corrected QT interval. However, plasma cisapride concentrations were higher than expected. Thus, in extremely elderly patients cisapride should be given once or twice a day rather than three times. 

Pantoprazole 40 mg/day and pantoprazole 40 mg/day plus cisapride 20 mg bd for 8 weeks have been compared in the treatment of gastro-esophageal reflux disease in a multicenter, randomized, double-blind trial in 350 patients (4). The addition of cisapride did not significantly improve symptom control or healing rates. The frequency of adverse effects in the two groups was similar. Compliance was worse in the pantoprazole plus cisapride group. 

Despite the rigorous process for drug approval and regulation, several important medications have been removed from the market because of serious ADEs over the past 30 years. Examples of serious but uncommon effects include acute flank syndrome associated with suprofen," the gastrointestinal effects associated with nonsteroidal anti-inflammatory drugs (NSAIDs) in the elderly," troglitazone and the risk of hepatotoxicity," and the adverse effects of cisapride... 

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