Clarithromycin with Theophylline Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Theophylline

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 08, 2023

Interaction Effect

Theophylline toxicity (nausea, vomiting, palpitations, seizures)

Interaction Summary

Two studies demonstrated an approximate 20% increase in both peak and trough theophylline concentrations as well as theophylline area under the concentration-time curve (AUC) with concomitant clarithromycin use. A different study reported an increase of only 8% in the theophylline AUC during concomitant clarithromycin administration . Reports of clinical toxicity resulting from concurrent use are lacking. However, patients should be counseled regarding symptoms of theophylline toxicity, and monitoring of theophylline concentrations is recommended, especially in patients receiving high doses of theophylline or with baseline concentrations in the upper therapeutic range.

Severity

Minor

Onset

Delayed

Evidence

Probable

How To Manage Interaction

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

Mechanism Of Interaction

Decreased theophylline metabolism

Literature Reports

A) The steady-state peak and trough theophylline levels, as well as the AUC of theophylline, were increased approximately 20% when theophylline was coadministered with clarithromycin. Theophylline was given as a sustained-release preparation at doses of either 6.5 mg/kg or 12 mg/kg. Doses of clarithromycin were 250 mg or 500 mg every 12 hours .

B) Five nonsmoking volunteers completed a randomized, four-period crossover study to evaluate coadministration of clarithromycin, ciprofloxacin, and theophylline. Each treatment phase lasted seven days, with a single dose of theophylline 400 mg being given on day 6. Treatment regimens were as follows: ciprofloxacin 500 mg twice daily for seven days, clarithromycin 1000 mg twice daily for seven days, ciprofloxacin 500 mg plus clarithromycin 1000 mg twice daily for seven days, or a single dose of theophylline on day 6. The AUC of theophylline alone was 144 mg/h/mL, and averaged 151 mg/h/mL during treatment with clarithromycin. This represented a mean increase of only 8%, with the range from a 24% decrease to a 46% increase. The theophylline half-life was 9.8 hours when administered alone, and 10.5 hours when given with clarithromycin. Theophylline is metabolized by the cytochrome P-450 1A2 enzyme system, and clarithromycin is known to inhibit cytochrome P-450 3A4 enzymes. Based on the different metabolic pathways for theophylline and clarithromycin, a clinically important drug interaction is not expected to occur in the majority of patients .

C) Theophylline toxicity may occur with concomitant levofloxacin and clarithromycin therapy. Decreased theophylline clearance with the addition of levofloxacin in a 59-year-old Japanese male has been reported. The patient had a history of emphysema and was taking theophylline sustained-release 400 mg/day for several years and had stable therapeutic concentrations (5-10 mcg/mL trough concentrations). The patient was admitted to the hospital with aggravated emphysema and fever. A continuous intravenous infusion of aminophylline (500 mg/day) was initiated. The theophylline serum concentration remained at steady-state on day 4 (11.8 mcg/mL). On day 15, oral clarithromycin 400 mg/day was initiated. Intravenous aminophylline was discontinued and oral theophylline 800 mg/day in two divided doses was started. Levofloxacin was initiated on hospital day 18 because Pseudomonas aeruginosa was identified in a sputum culture. On day 20 theophylline serum concentration was 24 mcg/mL. The patient experienced stimulation, insomnia and tachycardia one day later. Theophylline dosage was reduced to 300 mg/day three times daily on day 22. On day 26 levofloxacin was discontinued. Theophylline serum concentration on day 39 was decreased to 6.5 mcg/mL. The decrease in theophylline clearance by combination therapy with levofloxacin and clarithromycin is due to the additive inhibition of theophylline metabolic pathways (catalyzed by CYP1A2 and CYP3A4) by levofloxacin and clarithromycin .

Clarithromycin Overview

• Clarithromycin is used to treat certain bacterial infections, such as pneumonia (a lung infection), bronchitis (infection of the tubes leading to the lungs), and infections of the ears, sinuses, skin, and throat. It also is used to treat and prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. It is used in combination with other medications to eliminate H. pylori, a bacterium that causes ulcers. Clarithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as clarithromycin 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.

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.