Drug Interactions between cisapride and Doc-Q-Lax

CONTRAINDICATED: Coadministration with grapefruit juice may increase the plasma concentrations of cisapride. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In a study of 14 healthy volunteers, administration with 250 mL of grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of cisapride (10 mg single dose) by 34% and 39%, respectively, compared to water. A second single-dose study involving 12 healthy volunteers demonstrated an increase of 68% and 51% in cisapride Cmax and AUC, respectively, compared to water. In another 10 healthy volunteers, repeated ingestion of double-strength grapefruit juice (200 mL three times a day for 2 days, then with a 10 mg dose of cisapride and at 0.5 and 1.5 hours afterwards) resulted in an 81% and 144% increase in mean cisapride Cmax and AUC, respectively, compared to water. A high degree of intersubject variability in the grapefruit juice effect was observed in all three studies, but no patient experienced any changes in heart rate, blood pressure, or QT interval. However, high plasma levels of cisapride have been associated with prolongation of the QT interval on the ECG; ventricular arrhythmias including ventricular tachycardia, ventricular fibrillation, and torsade de pointes; cardiac arrest; and sudden death.

GENERALLY AVOID: Coadministration with red wine may increase the plasma concentrations of cisapride in susceptible individuals. The exact mechanism of interaction is unknown but is believed to involve inhibition of CYP450 3A4 in the gut wall similar to grapefruit juice. In 12 healthy volunteers, administration with 250 mL of red wine (cabernet sauvignon) produced only minor and statistically insignificant changes in cisapride pharmacokinetics compared to water. However, one subject had a doubling in cisapride AUC and Cmax with red wine. The same subject also had the largest interaction with grapefruit juice, which suggests that a significant interaction may occur in certain individuals, perhaps those with a preexisting high intestinal CYP450 3A4 content.

MANAGEMENT: Patients receiving cisapride therapy should avoid the consumption of grapefruits and grapefruit juice. Because a significant interaction may occur with red wine in the occasional patient, red wine should preferably be avoided also during cisapride therapy.

GENERALLY AVOID: Chronic use of stimulant laxatives may decrease the absorption of fat-soluble vitamins (A, D, E, and K) and minerals such as calcium, potentially leading to deficiencies. This effect is due to accelerated intestinal transit time, which reduces nutrient absorption.

MANAGEMENT: To minimize this risk, limit the use of stimulant laxatives to short-term or occasional use.

The use of stimulant laxatives is contraindicated in patients with or who may have acute surgical abdomen or appendicitis. These patients may be candidates for emergency surgery. Stimulant laxatives should also not be administered to patients with abdominal pain, particularly if the cause has not been determined.

The use of stimulant laxatives is contraindicated in patients with anal or rectal fissures. These preparations may cause irritation, burning sensation, and proctitis.

The use of cisapride is contraindicated in patients with cardiac disease. Serious cardiac arrhythmias, including ventricular arrhythmias and torsades de pointes associated with QT prolongation have been rarely associated with the use of cisapride, especially when taken in conjunction with other medications known to prolong the QT interval.

The use of cisapride is contraindicated in patients with gastrointestinal hemorrhage, mechanical obstruction, or perforation. Enhanced gastrointestinal motility could be harmful in these patients.

The use of laxatives is contraindicated in patients with intestinal obstruction disorders. Patients with intestinal obstruction disorders may need their underlying condition treated to correct the constipation. Some laxatives require reduction in the colon to their active form to be effective which may be a problem in patients with intestinal obstruction.

The use of laxatives is contraindicated in patients with intestinal obstruction disorders. Patients with intestinal obstruction disorders may need their underlying condition treated to correct the constipation. Some laxatives require reduction in the colon to their active form to be effective which may be a problem in patients with intestinal obstruction.

The use of cisapride is contraindicated in patients with gastrointestinal hemorrhage, mechanical obstruction, or perforation. Enhanced gastrointestinal motility could be harmful in these patients.

The use of cisapride is contraindicated in patients with gastrointestinal hemorrhage, mechanical obstruction, or perforation. Enhanced gastrointestinal motility could be harmful in these patients.

The use of laxatives is contraindicated in patients with inflammatory bowel disease. Patients with inflammatory bowel disease may experience colonic perforation with use of stimulant laxatives.

The use of laxatives is contraindicated in patients with inflammatory bowel disease. Patients with inflammatory bowel disease may experience colonic perforation with use of stimulant laxatives.