Proton pump inhibitors (PPI) and levothyroxine (LT4) are arguably the most widely used medications, especially in the elderly. Due to its small therapeutic index, the effect on levothyroxine absorption is particularly important since they are often co-ingested. This article highlights the relationship and effect of PPI on LT4.

Proton pump inhibitors' effect on levothyroxine absorption 

It is well known that the degradation of LT4 before its absorption in the intestine requires an acidic gastric pH. As a result, several in vitro experiments have shown that an increase in gastric pH influences the LT4 tablet's dissolution. PPIs have been added to the list of factors influencing gastrointestinal absorption of levothyroxine of significant clinical importance because they inhibit the secretion of gastric acid by covalent attachment to the H + /K + ATPase enzyme.

Administering LT4

When it comes to the proper timing of LT4 administration, it is generally advised that tablets be taken before breakfast while fasting. PPIs, on the other hand, are normally taken in the morning before breakfast, which is one of the key reasons that the co-administration of these two medications is a source of concern, especially for physicians who prescribe and follow up patients.

The relationship between PPI and LT4 has long been a point of contention. According to a comprehensive review of the literature, the latest oral solution formulation of LT4 (liquid and soft gel) will correct the impact of PPI on LT4 absorption and also has been shown to overcome malabsorption problems caused by some medications, coffee, and gastrointestinal diseases. A crossover analysis found a substantial reduction in TSH levels after transitioning from the tablet formulation to the liquid formulation while retaining PPI co-ingestion in patients whose LT4 treatment is ineffective after concurrent usage of LT4 and PPI.

The findings

Similarly, a major population-based sample of patients who had at least three LT4 medications prior to the start of the study found that PPI interferes with LT4 and that the relationship was clinically meaningful in 5–6% of those patients. Surprisingly, some research found that PPI co-ingestion had little effect on LT4 absorption. A pilot research conducted in patients with primary hypothyroidism who had been using a stabilised levothyroxine dosage for approximately one year before the start of the study found that omeprazole had little effect on LT4 therapy in hypothyroid patients. PPI administration had no effect on LT4 absorption in two pharmacokinetic trials in healthy volunteers.

1. In the research study by Sachmechi et al, 19% of subjects had TSH levels greater than 5 IU/mL after PPI ingestion, necessitating a 35% mean rise in LT4 dose.
2. In a study by Centanni et al, a 37 per cent increase in the median LT4 dose was required to re-establish a lower TSH level.

Recently, a systematic analysis of interventional and observational trials comparing TSH levels before and after concurrent use of LT4 and PPI was conducted. Five thousand twelve distinct papers were observed. Seven trials were included after assessing and applying eligibility requirements. The included studies differed significantly in terms of design, sample size, and inclusion and exclusion criteria, management regimen, and demographical parameters. TSH levels increased after LT4 and PPI intake in all of the studies included, and the majority of these increases were statistically important. The use of LT4 and PPI at the same time resulted in a substantial rise in TSH levels. However, considering the limited number of trials, further research is required to determine if PPI interferes with LT4 intestinal absorption.

Conclusion

Taking all of the data into account, the researchers concluded that, while PPI co-ingestion impacts TSH levels numerically, the influence is modest since most findings stay within the normal range. However, for a certain subset of people, especially those who have issues with compromised absorption for other causes, this finding could have a greater therapeutic effect. As a result, additional interventions, especially randomised controlled trials, are required to determine the effect of PPI consumption on LT4 absorption.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.