Diazepam with Theophylline Interaction Details

Brand Names Associated with Diazepam

Brand Names Associated with Theophylline

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 19, 2023

Interaction Effect

Decreased benzodiazepine effectiveness

Interaction Summary

Theophylline has been shown to reverse the sedative effects of benzodiazepines. A larger dose of benzodiazepine may be needed to produce sedation in a theophylline-treated patient. Respiratory depression may occur if theophylline is discontinued without a reduction of the benzodiazepine dose .

Severity

Moderate

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Monitor the patient for benzodiazepine clinical effectiveness. A larger than usual benzodiazepine dose may be required in a theophylline-treated patient. Benzodiazepine toxicity (respiratory depression, sedation, dizziness, ataxia, weakness, decreased cognition or motor performance) may occur if theophylline is discontinued without a subsequent reduction in the benzodiazepine dose.

Mechanism Of Interaction

Theophylline blocks adenosine receptors

Literature Reports

A) Eight healthy male volunteers participated in a study which demonstrated the antagonistic properties of theophylline on diazepam-induced psychomotor impairment. Subjects received an oral dose of diazepam 0.25 mg/kg, followed 40 minutes later by an intravenous infusion of 100 mL normal saline with or without theophylline 4.4 mg/kg. All subjects were tested twice: one time receiving theophylline and the other time receiving placebo. Theophylline reversed some of the diazepam-induced psychomotor impairment as measured by the digit symbol substitution test, card sorting, and three questionnaires which measured mood, anxiety, and distress. The antagonism caused by theophylline may be attributed to the stimulant action caused by methylxanthines on the central nervous system through adenosine receptor blockade .

B) Intravenous theophylline was reported to reverse the sedation produced by intravenous diazepam in patients undergoing genitourinary surgery. Patients were given intravenous doses of diazepam during surgery to maintain deep sedation, followed by administration of intravenous aminophylline (60 to 120 mg) or normal saline postoperatively. Rapid reversal of sedation occurred in aminophylline patients as compared to no response in saline patients . Other studies and case reports have also shown that theophylline antagonizes the sedative effects of diazepam .

C) Three case reports described patients who had the sedative effects of lorazepam reversed postoperatively by the administration of aminophylline 1 mg/kg intravenously . This same aminophylline dose was used to reverse the sedative effects of midazolam in three other patients . Theophylline also was demonstrated to reverse the sedative and psychomotor properties of flunitrazepam in healthy volunteers .

D) Less successful rates have been reported when utilizing aminophylline to reverse benzodiazepine oversedation . Of the six patients reported, all of whom had received midazolam, five patients showed no change in the level of consciousness after the administration of aminophylline 75 mg. One patient did experience quick and sudden awakening after aminophylline was given. The author suggests that there may be wide individual variations within the population to the effects of aminophylline antagonism on benzodiazepines .

E) To determine the mechanism by which theophylline antagonizes benzodiazepines, oral alprazolam 1 mg daily for seven days was administered to six patients who were receiving theophylline and to seven patients who were not receiving theophylline treatment. Serum alprazolam levels were significantly lower in patients on concurrent theophylline therapy, and the levels continued to decrease during each day of the study. In patients who were not receiving theophylline, serum alprazolam levels were within the therapeutic range. The authors concluded that the antagonism of the anxiolytic effects of benzodiazepines by theophylline may be due to decreased serum benzodiazepine levels in these patients .

Diazepam Overview

• Diazepam is used to relieve anxiety and to control agitation caused by alcohol withdrawal. It is also used along with other medications to control muscle spasms and spasticity caused by certain neurological disorders such as cerebral palsy (condition that causes difficulty with movement and balance), paraplegia (inability to move parts of the body), athetosis (abnormal muscle contractions), and stiff-man syndrome (a rare disorder with muscle rigidity and stiffness). Diazepam is also used along with other medications to control seizures. Diazepam is in a class of medications called benzodiazepines. It works by calming abnormal overactivity in the brain.

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.