Safety of drug use in patients with a primary mitochondrial disease: An international Delphi-based consensus.

Maaike C De Vries,Yi Shiau Ng,Michelangelo Mancuso,Amel Karaa,Robert Mcfarland,Costanza Lamperti,Gráinne S Gorman,Mar O'Callaghan,Frans G M Russel,Shamima Rahman,Laurence Bindoff,Robert D S Pitceathly,Mitchell E Allen,Tom J J Schirris,Kristin N Varhaug,Nandaki Keshavan,David A Brown

doi:10.1002/jimd.12196

Abstract

Clinical guidance is often sought when prescribing drugs for patients with primary mitochondrial disease. Theoretical considerations concerning drug safety in patients with mitochondrial disease may lead to unnecessary withholding of a drug in a situation of clinical need. The aim of this study was to develop consensus on safe medication use in patients with a primary mitochondrial disease. A panel of 16 experts in mitochondrial medicine, pharmacology, and basic science from six different countries was established. A modified Delphi technique was used to allow the panellists to consider draft recommendations anonymously in two Delphi rounds with predetermined levels of agreement. This process was supported by a review of the available literature and a consensus conference that included the panellists and representatives of patient advocacy groups. A high level of consensus was reached regarding the safety of all 46 reviewed drugs, with the knowledge that the risk of adverse events is influenced both by individual patient risk factors and choice of drug or drug class. This paper details the consensus guidelines of an expert panel and provides an important update of previously established guidelines in safe medication use in patients with primary mitochondrial disease. Specific drugs, drug groups, and clinical or genetic conditions are described separately as they require special attention. It is important to emphasise that consensus‐based information is useful to provide guidance, but that decisions related to drug prescribing should always be tailored to the specific needs and risks of each individual patient. We aim to present what is current knowledge and plan to update this regularly both to include new drugs and to review those currently included.

Highlights

Mitochondrial diseases are a group of inherited metabolic disorders that can present at any age and often exhibit multisystem involvement and high morbidity and mortality.[1]
16 experts in mitochondrial medicine, pharmacology and basic science provided their professional opinion concerning the safe use of medications in patients with primary mitochondrial disease, to assist clinician and patient decision-making
It is important to emphasise that consensus-based information is useful to provide guidance, but that decisions related to drug prescribing should always be tailored to the specific needs and risks of each individual patient

Summary

Introduction

Mitochondrial diseases are a group of inherited metabolic disorders that can present at any age and often exhibit multisystem involvement and high morbidity and mortality.[1]. Important considerations in the management of patients with mitochondrial diseases include early treatment of organ-specific complications and avoidance of potential triggers of decompensation including catabolic stressors (eg, fasting, intercurrent illness, pyrexia, trauma, or surgery) or medications that are toxic to mitochondrial function.[3]. For pharmacological treatment of patients risk-benefit considerations and a search for safer, better tolerated or more effective alternatives are part of normal clinical practice. Prescribing drugs to patients with mitochondrial disease is associated with the additional consideration of the drug's potential to negatively influence mitochondrial function.[4] Due to the heterogeneity in manifestations of mitochondrial disease, reported effects of a pharmacologic agent in an individual patient do not automatically account for all mitochondrial patients

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