Can Celiac Disease Impact Drug Therapy in Your Patients?

Celiac disease is an autoimmune disorder that renders those affected with an intolerance to gluten, a protein found in many common grains. It occurs in approximately 1% of the population of the United States and Europe.¹

People with celiac disease that ingest gluten generally experience an inflammatory reaction, manifested as gastrointestinal upset, diarrhea, and abdominal distension. Celiac disease is also associated with other chronic conditions, such as anemias and malabsorption of some critical vitamins. Alterations of the gastrointestinal tract, rates of gastric emptying, and gastric pH are responsible for altered vitamin and mineral absorption.^{2, 3} Intestinal CYP3A4 levels may also be disrupted, which may have implications in first-pass metabolism for some drugs that are substrates for this drug metabolizing enzyme.⁴ This has led some to investigate the potential impact of celiac disease on drug absorption. This would be of interest to pharmacists since altered drug absorption can have pharmacokinetic consequences and has the potential to impact overall drug therapy.

A comprehensive review on this topic was published in 2013 by Tran et al.The review considered absorption studies in subjects with celiac disease, and the authors summarized the literature available on a handful of drugs, including acetaminophen, aspirin, propranolol, levothyroxine, methyldopa, and some antibiotics.They reported that many studies had conflicting results. Some reports show an altered gastrointestinal environment and a significant difference in drug absorption in patients with celiac disease. Other reports did not show any absorption differences between those with and without the disease. It was noted that many of the studies considered for their analysis had small sample sizes and were not well powered. The authors concluded that there is the potential for altered drug absorption and that healthcare professionals should be cautious when initiating drug therapy.⁵

Another review on the topic of celiac disease and the potential impact on cardiovascular drug absorption was published in 2014. This review considered many of the same medications previously explored by Tran et al, with a focus on cardiovascular agents. The authors also expressed concern that many cardiovascular drugs may have altered absorption in celiac disease, but there are few published studies that are convincing enough for concrete clinical decision making. The authors also stressed the need for more studies that consider patients with celiac disease, as well as caution when initiating cardiovascular pharmacotherapeutic regimens.⁶

Based on the research available, it is clear that patients with celiac disease can exhibit altered absorption of many different substrates. Unfortunately, altered drug absorption and disposition are not well studied in this population. It is likely that future studies will elucidate any impact celiac disease has on drug disposition, as this disorder has been getting more attention in recent years. There is some preliminary evidence suggesting that celiac disease may alter drug absorption, but the degree and prevalence of this has yet to be confirmed with large prospective studies. Pharmacists should be cautious when making therapeutic recommendations for patients with celiac disease and consult the available literature when possible.

Increased monitoring for efficacy and adverse effects is advisable when starting a new medication regimen in patients with celiac disease.

References

1. Catassi C, Gatti S, Fasano A. The new epidemiology of celiac disease. J Pediatr Gastro Nutrition. 2014;S7-S9.

2. Perri F, Pastore M, Zicolella A, Annese V, Quitadamo M, Andriulli A. Gastric emptying of solids is delayed in celiac disease and normalizes after gluten withdrawal. Acta Paediatrica. 2000;8:921-25.

3. Caruso R, Pallone F, Stasi E, Romeo S, Monteleone G. Appropriate nutrient supplementation in celiac disease. Ann Intern Medicine. 2013;8:522-31.

4. Lang CC, Brown RM, Kinirons MT, et al. Decreased intestinal CYP3A in celiac disease: Reversal after successful gluten?free diet: A potential source of interindividual variability in first?pass drug metabolism. Clin Pharm Ther. 1996;1:41-46.

5. Tran TH, Smith C, Mangione RA. Drug absorption in celiac disease. Amer J Health-System Pharm. 2013;24.

6. Wang I, Hopper I. Celiac Disease and Drug Absorption: Implications for Cardiovascular Therapeutics. Cardio Ther. 2014;6:253-56.