Diazepam with Erythromycin Interaction Details

Brand Names Associated with Diazepam

Brand Names Associated with Erythromycin

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

Interaction Effect

Increased benzodiazepine toxicity (CNS depression, ataxia, lethargy)

Interaction Summary

Macrolide antibiotics may inhibit hepatic enzymes responsible for benzodiazepine metabolism leading to increased plasma concentrations of benzodiazepines through reduced clearance, prolonged half-life, and increased volume of distribution.

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Observe patients receiving concurrent macrolide antibiotics and benzodiazepines for enhanced CNS effects. Warn patients regarding potential for drug hangover. Smaller benzodiazepine doses (dose reduction by 50% to 75%) may be required after two to four days of concurrent macrolide antibiotic dosing.

Mechanism Of Interaction

Decreased hepatic metabolism; decreased clearance

Literature Reports

A) An 8-year-old boy undergoing adenoidectomy was premedicated with oral midazolam 0.5 mg/kg and oral atropine 0.03 mg/kg, followed in 1 hour by erythromycin 400 mg IV. The patient lost consciousness 40 minutes later after 200 mg had been infused; other vital signs remained normal, and he regained consciousness after 45 minutes. At 170 minutes post-medication, his midazolam plasma concentration was 134 ng/mL (411 nanomoles/L [nmol/L]). Six other children who were similarly premedicated (midazolam 0.5 mg/kg and atropine 0.03 mg/kg) but did not receive erythromycin had a mean midazolam level of 73 ng/mL (224 nmol/L) .

B) In a study involving normal volunteers, erythromycin (333 mg TID for 3 days) increased the peak levels of triazolam by 50%, increased the half-life from 4 to 6 hours, and decreased the volume of distribution .

C) A double-blind, placebo-controlled study of healthy volunteers has found that clearance of intravenously administered midazolam is reduced by about 50% following 5 days of erythromycin therapy versus placebo .

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.

Erythromycin Overview

• Erythromycin is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including bronchitis, pneumonia, Legionnaires' disease (a type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing); diphtheria (a serious infection in the throat); sexually transmitted diseases (STD), including syphilis; and ear, intestine, gynecological, urinary tract, and skin infections. It also is used to prevent recurrent rheumatic fever. Erythromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as erythromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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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.