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Drug Interactions between Cardizem CD and etrasimod

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

dilTIAZem etrasimod

Applies to: Cardizem CD (diltiazem) and etrasimod

Consumer information for this interaction is not currently available.

MONITOR: The risk of transient bradycardia and atrioventricular (AV) block may be increased during initiation of etrasimod treatment in patients receiving other drugs that slow the heart rate or AV conduction such as beta-blockers, certain calcium channel blockers (e.g., diltiazem, verapamil), and digitalis. Etrasimod may cause a decrease in heart rate during initiation of therapy. In the randomized placebo-controlled studies UC-1 and UC-2, following an initial dose of 2 mg, the greatest mean decrease in heart rate from baseline was 7.2 bpm and occurred at hour 2 (UC-2) and hour 3 on day 1. In studies UC-2 and UC-3, bradycardia was reported on day 1 in 2.9% of patients on etrasimod compared to none in the placebo group. On Day 2, bradycardia was reported in 1 patient (0.3%) treated with etrasimod compared to none in the placebo group. Overall, subjects who experienced bradycardia were generally asymptomatic. Few subjects experienced symptoms such as dizziness, and these symptoms resolved without intervention. Initiation of etrasimod treatment has also resulted in transient AV conduction delays. Initiation of etrasimod in patients stabilized on beta blockers did not cause additive heart rate reduction. However, the effects on heart rate reduction from initiating a beta blocker or other drugs that may decrease the heart rate in patients stabilized on etrasimod therapy are unknown.

MANAGEMENT: Advice from a cardiologist should be sought before initiation of beta blockers or drugs that may decrease heart rate (e.g., calcium channel blockers) in patients on a stable dose of etrasimod. Etrasimod can be initiated in patients stabilized on beta blockers. Cardiologist advice should also be sought if etrasimod is considered for use in patients with significant QT prolongation (QTcF greater than 450 msec in males or 470 msec in females), patients with arrhythmias requiring treatment with Class 1a or Class III antiarrhythmic agents, patients with unstable ischemic heart disease, heart failure, history of cardiac arrest, cerebrovascular disease, or uncontrolled hypertension. The use of etrasimod in patients with a history of Mobitz type I second-degree AV block is considered contraindicated unless the patient has a functioning pacemaker.

References

  1. "Product Information. Velsipity (etrasimod)." Pfizer U.S. Pharmaceuticals Group (2023):

Drug and food interactions

Moderate

dilTIAZem food

Applies to: Cardizem CD (diltiazem)

Alcohol can lower your blood pressure and add to the effects of dilTIAZem. You may experience dizziness, lightheadedness, fainting, or a rapid heartbeat if you drink alcohol with dilTIAZem, especially when you first start taking the medication or just after a dose increase. Grapefruit juice may also increase the effects of dilTIAZem in some people by increasing its levels in the blood. You may want to limit alcohol intake and avoid excessive consumption of grapefruit and grapefruit juice during treatment with dilTIAZem. However, if you have been regularly consuming grapefruit or grapefruit juice with dilTIAZem, do not alter the amounts of these products in your diet without first talking to your doctor or other healthcare professional. Contact your doctor if your condition changes or you experience increased side effects of dilTIAZem such as headache, irregular heartbeat, swelling, unexplained weight gain, or chest pain. Orange juice is not expected to interact.

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Moderate

etrasimod food

Applies to: etrasimod

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with moderate inhibitors of CYP450 3A4 such as grapefruit juice may increase the plasma concentrations of etrasimod in patients that are poor CYP450 2C9 metabolizers (e.g., *2/*3, *3/*3). Etrasimod is primarily metabolized by the CYP450 3A4, CYP450 2C8, and CYP450 2C9 isoenzymes. Pharmacokinetic studies reported that no single enzyme appears to dominate etrasimod elimination and that the involvement of multiple CYP450 isoforms reduces the likelihood of drug-drug interactions when only a single CYP450 isoform is strongly or moderately inhibited by a coadministered drug. In clinical drug interaction studies, when etrasimod was administered with the dual moderate CYP450 2C9 and 3A4 inhibitor fluconazole at steady-state levels, etrasimod systemic exposure (AUC) increased by 84%. However, concomitant use with the potent CYP450 3A4 inhibitor itraconazole increased the AUC of etrasimod by 32%, which was not considered by the manufacturer to be clinically significant. The effect on etrasimod systemic exposure in CYP450 2C9 intermediate metabolizers (e.g., *1/*2, *1/*3, *2/*2) treated with less potent CYP450 3A4 inhibitors is not known. Increased plasma concentrations of etrasimod may increase the risk of infection, bradyarrhythmia, AV conduction delays, elevated transaminase levels, and macular edema.

MANAGEMENT: Until further information is available, the consumption of grapefruit and grapefruit juice in combination with moderate to potent CYP450 2C8 inhibitors such as gemfibrozil should be avoided or limited during treatment with etrasimod in patients who are poor CYP450 2C9 metabolizers. Caution is recommended with grapefruit products consumption in patients who are intermediate CYP450 2C9 metabolizers. Patients should be advised to notify their physician if they experience potential adverse effects of etrasimod.

References

  1. "Product Information. Velsipity (etrasimod)." Pfizer U.S. Pharmaceuticals Group (2023):
  2. Lee C, Taylor C, Tang Y, Caballero LV, shan k, Randle A, Grundy JS "Effects of fluconazole, gemfibrozil, and rifampin on the pharmacokinetics, safety, and tolerability of etrasimod https://gut.bmj.com/content/71/Suppl_1/A142.1" (2022):
Moderate

dilTIAZem food

Applies to: Cardizem CD (diltiazem)

Using dilTIAZem together with multivitamin with minerals can decrease the effects of dilTIAZem. Talk with your doctor before using dilTIAZem and multivitamin with minerals together. You may need a dose adjustment or need your blood pressure checked more often if you take both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.