Article of the Week

 

We will be posting commentaries on articles relating to internal medicine and endocrinology that we think are of interest.

 

July 8th, 2021

A retrospective study of adverse effects of mycophenolate mofetil administration to dogs with immune-mediated disease

 

There are few publications that describe adverse events from MMF administration to dogs. Diarrhea, vomiting, and inappetence are the most frequently reported. In an experimental study in dogs, dose-limiting gastrointestinal (GI) adverse events (AEs) from MMF occurred at a dose of 60 mg/kg/day. Additionally, MMF-induced GI AEs were noted in a case series of 5 dogs with IMHA in which the median dose of MMF administered was 36.9 mg/kg/day (range, 27.8-41.1 mg/kg/day).  Diarrhea occurred in 17% of 30 dogs with IMHA that were administered MMF at a median dose of 20.5 mg/kg/day.  In a case series of 5 dogs with ITP, when MMF was prescribed as a single agent at a median dose of 17mg/ kg/day, 2 of the dogs had diarrhea and inappetence.  In a study of 25 dogs with meningoencephalomyelitis that were administered MMF at a mean dose of 20.05 mg/kg/day, 2 dogs developed vomiting and decreased appetite. In a prospective study in 10 dogs with sudden acquired retinal degeneration syndrome that were administered MMF at a dosage of 20 mg/kg/day, 2 dogs experienced GI adverse events that resolved with dosage reduction of MMF by 20%. It was reported that 6 (42.9%) of 14 dogs with immune-mediated skin disease that were treated with MMF at mean dosage of 29.4 mg/kg/day experienced GI AEs.  Although these studies describe AEs from MMF at a wide range of doses, the number of the cases in most reports was low and case details were not well documented.

 

In humans, females have significantly higher GI adverse event scores compared to males suggesting a sex-related effect. In addition, adverse events in dogs affecting body systems other than the GI system have not been well described. In the study of immune-mediated skin disease treated with MMF in 14 dogs, hepatotoxicity or bone marrow suppression was not observed. Other veterinary studies have not specifically examined MMF associated adverse events in other body systems in detail.

 

The purpose of the current study is to describe the types and frequency of adverse events likely to be associated with administration of MMF to dogs with naturally occurring immune-mediated diseases.

 

Background: Information regarding adverse events (AEs) of mycophenolate mofetil (MMF) is limited.

 

Objectives: To evaluate the types and frequency of potential AEs of MMF in dogs with immune-mediated disease.

 

Animals: One hundred thirty-one dogs treated with MMF for management of suspected immune-mediated disease.

 

Methods: Retrospective study. Medical records were reviewed to find and group suspect AEs in gastrointestinal (GI), hematologic, and other categories. Age, dosage, body weight, and sex were analyzed between dogs with and without AEs by using the Mann-Whitney U-test and chi-squared test.

 

Results: The median starting dosage of MMF was 17.5 mg/kg/day (interquartile range [IQR] = 15.1-20.6 mg/kg/day) and the median treatment duration was 56 days (IQR = 14-236 days). Mycophenolate mofetil was prescribed for immune-mediated hemolytic anemia (n = 31), immune-mediated thrombocytopenia (n = 31), pemphigus foliaceus (n = 15), immune-mediated polyarthritis (n = 12), and others (n = 42).

 

Overall, potential AEs of MMF were observed in 34 of 131 dogs (GI 24.4% [31/127], neutropenia 4% [3/76], anemia 4% [1/25], thrombocytopenia 4.0% [1/25], and dermatologic 1.5% [2/131]). There were no significant differences among dogs with

(n = 37) or without potential AEs (n = 94) in regards to sex, age, body weight, or dosage of MMF (P = .06, .13, .24, and .26, respectively).

 

Conclusions and Clinical Importance: In the dogs administered MMF, GI AEs were most common. Since potential hematologic and dermatologic AEs developed in a few dogs, clinicians should be aware of these when prescribing MMF to dogs with immune-mediated disease.