Theophylline and Nifedipine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Theophylline
Nifedipine
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Alterations of the theophylline serum concentration
Interaction Deep Dive
Concurrent administration of NIFEdipine and theophylline has been reported to cause an increase, a decrease, or no change in theophylline serum concentrations1245683. 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 7.
Why it happens (mechanism)
Unknown
Literature reports
5 reports — tap to read
a) Concomitant administration of NIFEdipine and theophylline resulted in theophylline toxicity in a 73-year-old woman with chronic obstructive pulmonary disease (COPD) 1. 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 2. 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 3.
d) NIFEdipine 10 mg orally four times a day for two weeks produced minimal beneficial effects in asthmatic patients receiving theophylline 4. 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 5. Others failed to find a significant interaction between theophylline at steady-state and coadministered NIFEdipine 20 mg twice daily for one week 6. 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 7.
Common questions
Can I take Theophylline and Nifedipine together?
Alterations of the theophylline serum concentration Always confirm with your pharmacist or prescriber before making any change.
How serious is the Theophylline and Nifedipine interaction?
It is rated minor. Usually limited clinical impact.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Theophylline or Nifedipine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (8)
- Harrod CS: Theophylline toxicity and nifedipine (letter). Ann Intern Med 1987; 106:480. PubMed
- Smith SR, Wiggins J, Stableforth DE, et al: Effect of nifedipine on serum theophylline concentrations and asthma control. Thorax 1987; 42:794-796. PubMed
- Yilmaz E, Canberk A, & Eroglu L: Nifedipine alters serum theophylline levels in asthmatic patients with hypertension. Fundam Clin Pharmacol 1991; 5:341-345. PubMed
- Garty M, Cohen E, Mazar A, et al: Effect of nifedipine and theophylline in asthma. Clin Pharmacol Ther 1986; 40:195-198. PubMed
- Sirmans SM, Pieper JA, Lalonde RL, et al: Effect of calcium channel blockers on theophylline disposition. Clin Pharmacol Ther 1988; 44:29-34. PubMed
- Smith SR, Haffner CA, & Kendall MJ: The influence of nifedipine and diltiazem on serum theophylline concentration-time profiles. J Clin Pharm Ther 1989; 14:403-408. PubMed
- Adebayo GI & Mabadeje AFB: Effect of nifedipine on antipyrine and theophylline disposition. Biopharm Drug Dispos 1990; 11:157-164. PubMed
- Christopher MA, Harman E, & Hendeles L: Clinical relevance of the interaction of theophylline with diltiazem or nifedipine. Chest 1989; 95:309-313. DOI
Keep reading about Theophylline
Keep reading about Nifedipine
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