Nifedipine with Theophylline Interaction Details

Brand Names Associated with Nifedipine

Brand Names Associated with Theophylline

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 20, 2023

Interaction Effect

Alterations of the theophylline serum concentration

Interaction Summary

Concurrent administration of NIFEdipine and theophylline has been reported to cause an increase, a decrease, or no change in theophylline serum concentrations. NIFEdipine was unable to significantly alter the clearance of antipyrine, suggesting that NIFEdipine does not affect the activity of the cytochrome P-450 system which is responsible for theophylline metabolism. Any interaction seen between these two drugs may be partially due to protein binding displacement .

Severity

Minor

Onset

Delayed

Evidence

Probable

How To Manage Interaction

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

Mechanism Of Interaction

Unknown

Literature Reports

A) Concomitant administration of NIFEdipine and theophylline resulted in theophylline toxicity in a 73-year-old woman with chronic obstructive pulmonary disease (COPD) . The patient had been stable on theophylline 375 mg twice daily for a year, with serum theophylline concentrations of 14 mcg/mL. NIFEdipine 10 mg twice daily for instituted for hypertension, and within two weeks the patient was hospitalized with increasing dyspnea. Her theophylline level was 41 mcg/mL, and theophylline was discontinued. Toxicity recurred upon rechallenge and the dose of theophylline was then decreased to 300 mg daily to enable combined therapy.

B) Eight patients in a double-blind, placebo controlled, crossover design study demonstrated that theophylline serum concentrations were decreased by NIFEdipine coadministration . Subjects received slow-release oral theophylline twice daily in a dose to ensure serum concentrations over 8 mcg/mL. Placebo or slow-release NIFEdipine 20 mg twice daily was then added to therapy for two weeks. Results showed a mean serum theophylline concentration of 9.6 mcg/mL after monotherapy, and 6.8 mcg/mL when NIFEdipine was coadministered. Three patients had serum theophylline concentrations of 4 mcg/mL or less after the addition of NIFEdipine, representing decreases of 64%, 56%, and 50% from the levels seen with placebo. No change in subjective or objective measurements of asthma control were observed during concomitant NIFEdipine and theophylline therapy.

C) Thirteen non-smoking female volunteers received slow-release theophylline 200 mg twice daily for 15 days, which provided an average steady-state theophylline serum concentration of 11.2 mcg/mL. When NIFEdipine 10 mg twice daily was added to the regimen for 15 days, no change in the serum theophylline concentration was observed. However, after 45 days of cotherapy with NIFEdipine and theophylline, serum theophylline levels averaged only 7.3 mcg/mL .

D) NIFEdipine 10 mg orally four times a day for two weeks produced minimal beneficial effects in asthmatic patients receiving theophylline . NIFEdipine did not significantly improve morning or evening peak expiratory flow rates (PEFR), symptom scores, or the number of daily albuterol inhalations required. No significant changes in PEFR were observed at 30, 60 or 120 minutes following oral NIFEdipine, and NIFEdipine did not significantly affect steady-state theophylline pharmacokinetics.

E) Twelve healthy volunteers received a single oral dose of theophylline 5 mg/kg alone, and after seven days of therapy with NIFEdipine 20 mg every eight hours in a randomized crossover fashion. When compared to control values, no significant changes in the theophylline area under the concentration-time curve (AUC), elimination rate constant, half-life, oral clearance, or apparent volume of distribution were observed when NIFEdipine was coadministered . Others failed to find a significant interaction between theophylline at steady-state and coadministered NIFEdipine 20 mg twice daily for one week . Maximum concentrations for theophylline were 8.47 mcg/mL when subjects received placebo and 10.21 mcg/mL during NIFEdipine administration. In one study, NIFEdipine did not alter the half-life or clearance of theophylline in six volunteers, but did significantly change the volume of distribution from a control value of 0.451 L/kg to 0.483 L/kg .

Nifedipine Overview

• Nifedipine is used to treat high blood pressure and to control angina (chest pain). Nifedipine is in a class of medications called calcium-channel blockers. It lowers blood pressure by relaxing the blood vessels so the heart does not have to pump as hard. It controls chest pain by increasing the supply of blood and oxygen to the heart.

• High blood pressure is a common condition and when not treated, 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.