Diltiazem with Tacrolimus Interaction Details

Brand Names Associated with Diltiazem

Brand Names Associated with Tacrolimus

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

Increased tacrolimus exposure and increased risk of toxicity

Interaction Summary

Concomitant use of tacrolimus with a mild or moderate CYP3A inhibitor may increase tacrolimus whole blood trough concentrations and the risk of serious toxicity (eg, neurotoxicity, QT prolongation). If coadministered, monitor tacrolimus blood levels and reduce the dose as needed, and monitor for tacrolimus-associated adverse effects.

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Concomitant use of tacrolimus with a mild or moderate CYP3A inhibitor may increase tacrolimus whole blood trough concentrations and the risk of serious toxicity (eg, neurotoxicity, QT prolongation). If coadministered, monitor tacrolimus blood levels and reduce the dose as needed, and monitor for tacrolimus-associated adverse effects.

Mechanism Of Interaction

Inhibition of CYP3A-mediated tacrolimus metabolism

Literature Reports

A) In a study involving 4 organ transplant patients, diltiazem increased tacrolimus plasma concentrations to create a tacrolimus-sparing effect. Two stable kidney transplant patients and 2 stable liver transplant patients who had been maintained on tacrolimus twice daily were treated with 7 incremental doses of diltiazem (0 to 180 mg/day) at intervals of 2 weeks or more. An increase in tacrolimus AUC of 26% and 67% occurred following the diltiazem 20 mg/day dose for the 2 kidney transplant patients. The maximum increase in tacrolimus AUC, 48% and 177%, occurred with diltiazem 180 mg/day in the 2 kidney transplant patients. The tacrolimus AUC did not increase in the 2 liver transplant recipients until a higher diltiazem dose was given (60 to 120 mg/day), and the AUC increases of 18% and 22% were lower than those reported for the kidney transplant recipients. Diltiazem also affects blood tacrolimus concentrations for longer than would be expected based on the half-life of diltiazem since the increase in tacrolimus AUC at 12 hours was similar to the increase from 12 to 24 hours when diltiazem was administered only in the morning (dose of 60 mg/day or more). The initial dosage of diltiazem should be 60 mg each morning followed by diltiazem 60 mg twice daily, depending on the magnitude of the tacrolimus-sparing response and the clinical situation .

Diltiazem Overview

• Diltiazem is used to treat high blood pressure and to control angina (chest pain). Diltiazem is in a class of medications called calcium-channel blockers. It works by relaxing the blood vessels so the heart does not have to pump as hard. It also increases the supply of blood and oxygen to the heart.

• High blood pressure is a common condition, and when not treated it can cause damage to the brain, heart, blood vessels, kidneys, and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

Tacrolimus Overview

• Tacrolimus (Astagraf XL, Envarsus XR, Prograf) is used along with other medications to prevent rejection (attack of a transplanted organ by the immune system of a person receiving the organ) in people who have received a kidney transplant. Tacrolimus (Prograf) is also used along with other medications to prevent rejection in people who have received a liver, lung, or heart transplant. Tacrolimus is in a class of medications called immunosupressants. It works by decreasing the activity of the immune system to prevent it from attacking the transplanted organ.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.