Tolerability of different oral iron supplements: a systematic review

Abstract

Objective:

A systematic review was conducted to analyze the tolerability of several oral iron supplements based on data obtained in available publications and to report the incidence of adverse effects (AEs) for each supplement both overall and gastrointestinal.

Methods:

Electronic databases – Medline, the Cochrane Library, and Embase were searched for studies published up to January 2009. Clinical or observational studies reporting data on the tolerability of oral iron supplements were included. Results were described statistically and a quasi-binomial logistic regression model was developed to evaluate and compare the tolerability of the supplements studied.

Results:

For this review 111 studies were included, with data on 10,695 patients. Ferrous sulfate with mucoproteose had the lowest incidence of AEs (4.1% for overall AEs, 3.7% for gastrointestinal AEs [GAEs]) and was used as the reference supplement in the regression model. Incidence rates of overall AEs for the other supplements were 7.3% for iron protein succinylate [GAEs: 7%; OR for AE compared to the reference supplement, 1.96], 23.5% for ferrous glycine sulfate [GAEs: 18.5%; OR: 5.90], 30.9% for ferrous gluconate [GAEs: 29.9%; OR: 11.06], 32.3% for ferrous sulfate without mucoproteose [GAEs: 30.2%; OR: 11.21], and 47.0% for ferrous fumarate [GAEs: 43.4%; OR: 19.87].

The differences in incidence of AEs between extended-release ferrous sulfate with mucoproteose and all other supplements except iron protein succinylate were statistically significant at p < 0.001. These findings are subject to some limitations as the designs and methodologies of the studies included show heterogeneity among them that has partially been counteracted by the large sample size provided by the substantial number of trials, which is considered a strength in tolerability studies.

Conclusion:

Extended-release ferrous sulfate with mucoproteose appears to be the best tolerated of the different oral iron supplements evaluated.

Keywords::

• Adverse effects
• Ferrous sulfate
• Iron deficiency
• Iron deficiency anemia; Mucoproteose
• iron tolerability

Transparency

Declaration of interest

This work was funded by Pierre Fabre Ibérica, S.A. All authors contributed to the conception and design of the study and the interpretation of data, and also had full access to all of the study data and can take responsibility for the integrity of the data and the accuracy of the data analysis.

Declaration of financial/other relationships

M.J.C-H., M.C-R., J.H-P., and L.P-E. have no relevant financial relationships to disclose. J.M. has disclosed that he is employed full-time by Pierre Fabre Ibérica S.A., as medical advisor. C.C-B. has disclosed that he has received a fee for a lecture to Pierre Fabre employees. S.P. has been consultant to and on the speakers’ bureau of the following: Sanofi Pasteur, MSD, Pfizer, Bayer Schering Pharma, Servier, Lilly, Pierre Fabre, Daiichi-Sankyo, Roche, Warner Chilcott, Amgen, Arkopharma and Boehringer-Ingelheim. CMRO peer reviewers of this manuscript have no relevant financial relationships to disclose.

Acknowledgments

The authors gratefully acknowledge Julia Lezcano and Vanita Garani for their assistance, Josep Maria Manresa and Isaac Subirana for their support in the statistical analysis, and Michael Herdman for translating and adapting the manuscript. The grant provided by Pierre Fabre Ibérica, S.A. has served to fund their support. The authors also thank the pharmaceutical companies that market the oral iron supplements studied for providing information on them.

Preliminary results of the present study were reported at the 13th World Congress on the Menopause, 8–11 June 2011, Rome, Italy, and published as an abstract in Climacteric 2011;4 (Suppl. 1):153 with the title “Tolerability of different oral iron formulations: a systematic review”.