Theophylline/Aminophylline

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Also indexed as:

Phyllocontin, Slo-Bid, Slo-Phyllin, Theo-24, Theo-Bid, Theo-Dur, Theocron, Theolair, Truphylline, Uni-Dur, Uniphyl

Combination List

Combination drug:

• Primatene Dual Action

Theophylline and aminophylline are bronchodilator drugs (i.e., drugs that open the lung passages) used to treat people with asthma. Aminophylline is a modified form of theophylline. Theophylline and aminophylline are used systemically (carried in the blood stream through the body) and have side effects throughout the body. Other drugs, which are administered by inhalation, are more commonly used to treat asthma, because they go directly to the lungs.

Herbs

Summary of Interactions

Depletion or interference	Magnesium Potassium Vitamin B6
Adverse interaction	Caffeine Pepper*
Side effect reduction/prevention	None known
Supportive interaction	None known
Reduced drug absorption/bioavailability	St. John's wort* Tannin-containing herbs such as green tea, black tea, uva ursi, black walnut, red raspberry, oak, and witch hazel
Other (see text)	Soy*

An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

Interactions with Supplements

Potassium and Magnesium

Preliminary evidence indicates that theophylline can promote potassium and magnesium deficiency.^{1, 2} Some doctors have noted a tendency for persons on theophylline to become deficient in these minerals. Therefore, supplementing with these minerals may be necessary during theophylline therapy. Consult with a doctor to make this determination.

Vitamin B6

Theophyline has been associated with depressed serum vitamin B6 levels in children with asthma³ and adults with chronic obstructive pulmonary disease.⁴ In a short-term study of healthy adults, theophylline reduced serum vitamin B6 levels and supplementation with vitamin B6 (10 mg per day) normalized vitamin B6 levels.⁵ Some doctors believe that it makes sense for people taking this drug to accompany it with 10 mg of vitamin B6 per day.

Soy

In a study of healthy volunteers given theophylline, ingesting daidzein (one of the major isoflavones in soy) in the amount of 200 mg twice a day for ten days inhibited the metabolism of theophylline, resulted in higher concentrations of the drug.⁶ The amount of daidzein used in this study was greater than what would be found in a normal portion of soy foods; it is not known whether consuming average amounts of soy would have a similar effect.

Interactions with Herbs

Pepper (Piper nigrum, Piper longum)

Piperine is a chemical found in black peppers. A human study found that single doses of piperine could increase blood levels of theophylline.⁷ Hypothetically, such an elevation could lead to increased theophylline side effects or dose reductions without loss of drug efficacy. However, further study is required before such conclusions are made. People should not change the amount of theophylline taken without consulting their physician.

Tannin-containing herbs

Herbs high in tannins can impair the absorption of theophylline.⁸ High-tannin herbs include green tea, black tea, uva ursi (Arctostaphylos uva-ursi), black walnut (Juglans nigra), red raspberry (Rubus idaeus), oak (Quercus spp.), and witch hazel (Hamamelis virginiana).

St. John's wort (Hypericum perforatum)

One case study of a 42-year old asthmatic woman reported that taking 300 mg per day of St. John's wort extract led to a significant decrease in blood levels of theophylline.⁹ Following discontinuation of St. John's wort, the patient's blood levels of theophylline returned to an acceptable therapeutic level. This may have occurred because certain chemicals found in St. John's wort activate liver enzymes that are involved in the elimination of some drugs.^{10, 11} Until more is known, people taking theophylline should avoid St. John's wort.

Other Interactions

Food

Low-carbohydrate, high-protein diets, charbroiled beef, and large amounts of cruciferous vegetables (broccoli, Brussels sprouts, cabbage, and cauliflower) can reduce theophylline activity.^{12, 13} High-carbohydrate, low-protein diets can increase theophylline activity and side effects.¹⁴ Sustained-release forms of theophylline should be taken on an empty stomach and should not be crushed or chewed.¹⁵ Liquid and non-sustained release theophylline products are best taken on an empty stomach, but they may be taken with food if stomach upset occurs.¹⁶ People with questions about theophylline and food should ask their prescribing doctor or pharmacist.

Caffeine

Large amounts of caffeine (a substance that is related to theophylline) may increase the activity and side effects of theophylline.¹⁷Coffee, tea, colas, chocolate, guaraná, and some supplement products contain caffeine. Limiting intake of caffeine-containing beverages and products to small amounts will avoid this interaction.

Soy

In a study of healthy volunteers given theophylline, ingesting daidzein (one of the major isoflavones in soy) in the amount of 200 mg twice a day for ten days inhibited the metabolism of theophylline, resulted in higher concentrations of the drug.¹⁸ The amount of daidzein used in this study was greater than what would be found in a normal portion of soy foods; it is not known whether consuming average amounts of soy would have a similar effect.

References

1. Rayssiguier Y. Hypomagnesemia resulting from adrenaline infusion in ewes: Its relation to lipolysis. Horm Metab Res 1977;9:309-14.
2. Smith SR, Gove I, Kendall MJ. Beta agonists and potassium. Lancet 1985;1:1394.
3. Shimizu T, Maeda S, Arakawa H, et al. Relation between theophylline and circulating vitamin levels in children with asthma. Pharmacology 1996;53:384-9.
4. Martinez de Haas MG, Poels PJ, de Weert CJ, et al. Subnormal vitamin B6 levels in theophylline users. Ned Tijdschr Geneeskd 1997;141:2176-9 [in Dutch].
5. Ubbink JB, Delport R, Becker PJ, Bissbort S. Evidence of a theophylline-induced vitamin B6 deficiency caused by noncompetitive inhibition of pyridoxal kinase. J Lab Clin Med 1989;113:15-22.
6. Peng WX, Li HD, Zhou HH. Effect of daidzein on CYP1A2 activity and pharmacokinetics of theophylline in healthy volunteers. Eur J Clin Pharmacol 2003;59:237-41.
7. Bano G, Raina RK, Zutshi U, et al. Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol 1991;41:615-7.
8. Brinker F. Interactions of pharmaceutical and botanical medicines. J Naturopathic Med 1997;7(2):14-20.
9. Nebel A, Schneider BJ, Baker RK, Kroll DJ. Potential metabolic interaction between St. John's wort and theophylline [letter]. Ann Pharmacother 1999;33:502.
10. Nebel A, Schneider BJ, Baker RK, Kroll DJ. Potential metabolic interaction between St. John's wort and theophylline [letter]. Ann Pharmacother 1999;33:502.
11. Mai I, Schmider J, et al. Unpublished results, May, 1999. Reported in: Johne A, Brockmöller, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St. John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66:338-45.
12. Threlkeld DS, ed. Respiratory Drugs, Bronchodilators, Xanthine Derivatives. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Feb 1991, 178-9a.
13. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 260.
14. Threlkeld DS, ed. Respiratory Drugs, Bronchodilators, Xanthine Derivatives. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Feb 1991, 178-9a.
15. Threlkeld DS, ed. Respiratory Drugs, Bronchodilators, Xanthine Derivatives. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Feb 1991, 178-9a.
16. Threlkeld DS, ed. Respiratory Drugs, Bronchodilators, Xanthine Derivatives. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Feb 1991, 178-9a.
17. Threlkeld DS, ed. Respiratory Drugs, Bronchodilators, Xanthine Derivatives. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Feb 1991, 178-9a.
18. Peng WX, Li HD, Zhou HH. Effect of daidzein on CYP1A2 activity and pharmacokinetics of theophylline in healthy volunteers. Eur J Clin Pharmacol 2003;59:237-41.

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Last Review: 01-21-2009

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The information presented in Aisle7 is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires February 2010.

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