Diltiazem with Theophylline Interaction Details

Brand Names Associated with Diltiazem

Brand Names Associated with Theophylline

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

Interaction Effect

Increased theophylline serum levels and risk of toxicity (nausea, vomiting, palpitations, seizures)

Interaction Summary

Concurrent administration of theophylline and diltiazem has been reported to reduce total body clearance of theophylline and increase serum half-life of theophylline in several studies. Other reports have found no changes in theophylline concentration or observed only slight increases (not statistically significant) in theophylline concentration during coadministration with diltiazem . Further clinical studies are necessary to confirm the extent of this interaction.

Severity

Moderate

Onset

Rapid

Evidence

Theoretical

How To Manage Interaction

Theophylline serum concentrations should be monitored when diltiazem is added, discontinued, or when dosing changes occur. Dose adjustments of theophylline may be necessary.

Mechanism Of Interaction

Decreased theophylline metabolism

Literature Reports

A) Concomitant administration of intravenous aminophylline and oral diltiazem has been reported to result in a reduction in the total body clearance and an increase in the elimination half-life of theophylline in healthy male subjects. The volume of distribution was unchanged during combined therapy. In smoking patients, the increase in theophylline half-life was greater than in non-smokers .

B) One study examined the effects of concurrent aminophylline and diltiazem administration in eight patients with bronchospastic airway disease. Patients were given a continuous infusion of aminophylline (12 mg per kg per day) until serum theophylline was at steady-state. After blood samples were taken, aminophylline therapy was reinitiated at the same dose, and diltiazem 60 mg three times daily for five days was added. On day 5 of diltiazem therapy, blood samples were taken again. During coadministration with diltiazem, theophylline half-life increased by 24%, and theophylline clearance decreased by 22% .

C) In a randomized, four-way crossover study, 12 healthy subjects received a single oral dose of theophylline (5 mg per kg), followed by either diltiazem 90 mg every eight hours, verapamil 120 mg every eight hours, nifedipine 20 mg every eight hours, or placebo, for a total of seven days. Another single dose of theophylline was then administered. Mean theophylline oral clearance decreased 12% after administration of diltiazem. In addition, theophylline half-life increased significantly from control values (8.6 hours vs. 9.9 hours). However, the authors concluded that the reduction in theophylline clearance was not likely to produce clinically significant increases in theophylline concentrations in most patients .

D) One study examined the effects of diltiazem or cimetidine on the inhibition of theophylline metabolism in nine healthy male volunteers. Subjects were pretreated with diltiazem 60 mg, cimetidine 400 mg, or placebo three times daily for three days before being given three doses of 200 mg oral theophylline. Diltiazem increased the half-life of theophylline and decreased the mean theophylline clearance. No differences were observed in the area under the concentration-time curve (AUC) or volume of distribution during concurrent therapy .

E) In contrast, another study of 21 subjects with chronic asthma showed that patients receiving theophylline (400 to 1500 mg per day) plus diltiazem doses of up to 480 mg per day or nifedipine 160 mg per day did not change theophylline concentration significantly . An additional study observed only a slight increase (not statistically significant) in theophylline concentration caused by 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.

Theophylline Overview

• Theophylline is used to prevent and treat wheezing, shortness of breath, and chest tightness caused by asthma, chronic bronchitis, emphysema, and other lung diseases. It relaxes and opens air passages in the lungs, making it easier to breathe.

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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.