Diltiazem with Triazolam Interaction Details

Brand Names Associated with Diltiazem

Brand Names Associated with Triazolam

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

Interaction Effect

Increased serum triazolam levels and increased intensity of sedation

Interaction Summary

A controlled study observed significant pharmacokinetic interactions between diltiazem and triazolam in healthy volunteers. Pretreatment with diltiazem resulted in 2.3-fold and 1.7-fold increases in the triazolam area under the concentration-time curve (AUC) and maximum concentration (Cmax), respectively. Diltiazem pretreatment was also associated with significantly increased pharmacodynamic effects of triazolam. Further controlled studies or case reports are necessary to confirm the clinical implications of this interaction.

Severity

Moderate

Onset

Rapid

Evidence

Probable

How To Manage Interaction

The concurrent use of triazolam and diltiazem should be avoided. If coadministration of these agents is necessary, monitor patients for symptoms consistent with increased serum triazolam concentrations (CNS depression, ataxia, lethargy). Downward triazolam dosage adjustments may be necessary.

Mechanism Of Interaction

Diltiazem inhibition of triazolam metabolism by cytochrome P450 isozymes

Literature Reports

A) In a randomized, 3-phase crossover study of seven healthy male volunteers, the pharmacokinetic and pharmacodynamic interactions between diltiazem and triazolam were studied. The subjects received diltiazem 60 mg or placebo three times daily for three days, followed by a single 0.25 mg dose of triazolam or placebo. Blood samples were taken and pharmacodynamic analysis of triazolam effects were performed throughout the study. Pretreatment with diltiazem significantly increased the area under the concentration-time curve (AUC) of triazolam by approximately 2.3-fold, from 8.0 +/- 2.4 ng/mL to 18.2 +/- 3.1 ng/mL. The mean triazolam maximum concentration (Cmax) was increased by approximately 1.7 times after pretreatment with diltiazem. No change was observed in triazolam time to maximum concentration (Tmax). Pharmacodynamic measurements of triazolam activity, as measured by peak saccadic velocity of eye movements (PSV), electroencephalogram (EEG), and visual analogue scale measurements (VAS), were also significantly changed after diltiazem pretreatment. The authors concluded that pretreatment with diltiazem markedly affects the pharmacokinetics of triazolam in addition to increasing the intensity of the sedative effects, and recommended that triazolam be avoided in patients taking diltiazem .

B) Increased clinical effects, such as prolonged sedation, can occur with coadministration of triazolam and diltiazem. Concomitant administration of triazolam and diltiazem may result in an increase in area under the curve (AUC) of triazolam by 3-4 fold and maximum plasma concentration by 2-fold, when compared to placebo. An increase in elimination half-life of triazolam by 1.5-2.5 fold has also been shown to occur during coadministration with diltiazem .

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.

Triazolam Overview

• Triazolam is used on a short-term basis to treat insomnia (difficulty falling asleep or staying asleep). Triazolam is in a class of medications called benzodiazepines. It works by slowing activity in the brain to allow sleep.

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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.