Drug Interactions between Acid Controller Complete Dual Action and ozanimod

GENERALLY AVOID: Due to the risk of bradycardia and atrioventricular (AV) block, the risk of QT prolongation and torsade de pointes arrhythmia may be increased during initiation of ozanimod treatment in patients receiving drugs that prolong the QT interval. Ozanimod can cause a decrease in heart rate during initiation of therapy, in two studies, following an initial dose of 0.23 mg, the greatest mean decrease from baseline in heart rate of 1.2 bpm occurred at hour 5 on day 1 and returned to near baseline at hour 6. Following continued up-titration, the maximal heart rate effect of ozanimod occurred on day 8. Heart rates below 40 bpm were not observed. Initiation of ozanimod without dose titration may result in greater decreases in heart rate. Initiation of ozanimod treatment has also resulted in transient AV conduction delays. Reportedly, with the administration of ozanimod at doses higher than the recommended dosage and without dose titration, first- and second-degree AV block occurred in healthy subjects. However, in two studies which utilized dose titration, second- or third-degree AV block was not reported in patients receiving ozanimod. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Ozanimod has not been studied in patients receiving drugs that can prolong the QT interval. Because bradycardia and AV block are recognized risk factors for QT prolongation and torsade de pointes arrhythmia, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties. Advice from a cardiologist should be sought if treatment with ozanimod is considered in patients with significant QT prolongation (QTcF greater than 450 msec in males or 470 msec in females), patients on concurrent therapy with QT prolonging drugs with a known risk of torsades de pointes or drugs that slow heart rate or AV conduction, or in patients with arrhythmias requiring treatment with Class 1a or Class III antiarrhythmic agents.

MONITOR: Bowel cleansing as well as overuse of certain laxatives may cause electrolyte loss and increase the risk of torsade de pointes ventricular arrhythmia in patients treated with drugs that prolong the QT interval. Electrolyte disturbances including hypokalemia and hypomagnesemia have been reported with laxative abuse and are known risk factors for torsade de pointes associated with QT interval prolongation.

MANAGEMENT: Patients treated with drugs that prolong the QT interval should exercise caution when self-medicating with laxatives. The recommended dosage and duration of use should not be exceeded. Patients treated with lactulose for more than six months should be monitored periodically for electrolyte imbalance. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.