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Microangiopathy associated with gemcitabine: a drug interaction with nab-paclitaxel? A case series and literature review

  • Pharmacodynamics
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Abstract

Purpose

Gemcitabine and nab-paclitaxel association can be used in first- or second-line treatment for metastatic pancreatic adenocarcinoma. Here, we report five cases of supposed gemcitabine-induced thrombotic microangiopathy (G-TMA), four of them with nab-paclitaxel. We assumed that nab-paclitaxel could be responsible for a potential drug interaction with gemcitabine, increasing the risk of thrombotic microangiopathy occurrence.

Methods

Clinicians reported cases of supposed G-TMA that were declared to the Pharmacovigilance center. We collected the patients’ data (clinical and biological characteristics), calculated an incidence rate of G-TMA in our center, and a Naranjo score for each patient. We also reviewed literature on a potential drug interaction between nab-paclitaxel and gemcitabine.

Results

Four patients were treated with nab-paclitaxel/gemcitabine and one with gemcitabine alone. The time onset of supposed G-TMA was 2 to 11 months. Patients developed anemia, thrombocytopenia, and renal failure. The incidence rate of supposed G-TMA was 2.7% in our center compared to 0.31% (Meyler’s Side Effect of Drugs) and 0.01% in the gemcitabine’s summary of product characteristics. Literature review outlined an increase of gemcitabine’s plasmatic concentrations induced by nab-paclitaxel (Drugs® website) and a potentiation of gemcitabine’s effect by nab-paclitaxel in murine models. This study showed that nab-paclitaxel inhibits cytidine deaminase’s activity (responsible for gemcitabine’s metabolism) and increases gemcitabine’s active metabolite concentrations (gemcitabine triphosphate) in tumor tissues.

Conclusion

High incidence rate of G-TMA was observed in our cohort due to a potential drug interaction between nab-paclitaxel and gemcitabine with an increased risk of developing G-TMA. Additional pharmacological and pharmaco-epidemiological investigations are mandatory to explore this hypothesis.

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Authors and Affiliations

  1. Pharmacy Department, DMU PRISME, APHP, Beaujon Hospital, 92110, Clichy, France

    Jeanne Allard, Mathilde Bonnet, Marie-Pauline Gagaille & Vincent Leclerc

  2. Department of Pancreatology, DMU DIGEST, APHP, Beaujon Hospital, 92110, Clichy, France

    Lucie Laurent

  3. Liver Cancer Unit, DMU DIGEST, APHP, Beaujon Hospital, 92110, Clichy, France

    Mohamed Bouattour

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  1. Jeanne Allard
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  2. Mathilde Bonnet
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  3. Lucie Laurent
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  5. Marie-Pauline Gagaille
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Jeanne ALLARD. The first draft of the manuscript was written by Jeanne ALLARD and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jeanne Allard.

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Allard, J., Bonnet, M., Laurent, L. et al. Microangiopathy associated with gemcitabine: a drug interaction with nab-paclitaxel? A case series and literature review. Eur J Clin Pharmacol 78, 1087–1093 (2022). https://doi.org/10.1007/s00228-022-03324-z

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