Page 1255 - Small Animal Internal Medicine, 6th Edition

CHAPTER 72 Treatment of Primary Immune-Mediated Diseases 1227

TABLE 72.4
VetBooks.ir Pharmacokinetic Interactions With Cyclosporine

WELL-DOCUMENTED
EFFECT OF THE
CONCOMITANT THERAPY REPORT OF INTERACTION
ON CYCLOSPORINE WITH MARKED EFFECTS ON ANECDOTAL REPORTS DOCUMENTED EVIDENCE OF
CONCENTRATION BLOOD LEVELS OF INTERACTION ABSENCE OF INTERACTION

Increase of concentrations Ketoconazole Nafcillin
Fluconazole Estradiol
Itraconazole
Diltiazem
Erythromycin
Clarithromycin
Norfloxacin
Phenytoin
Metoclopramide
Vitamin E (with Sandimmune)
No change of Metoclopramide Methylprednisolone
concentrations Cimetidine
Vitamin E (with Atopica)
Nonsteroidal
antiinflammatory drugs
Fluoroquinolones*
β-Lactam antibiotics
Decrease of concentrations Trimethoprim sulfonamides, Clindamycin
St. John’s wort

Drugs in italics documented in dogs or cats.
Text in bold, increase by >100%.
Regular text, increase or decrease by 50% to 100%.
*Except norfloxacin.
Modified from Guaguere E et al.: A new drug in the field of canine dermatology. Vet Dermatol 2004;15:61.

antiinflammatory effects. Leflunomide is most commonly MYCOPHENOLATE MOFETIL
used to treat RA in people. In dogs, leflunomide was first
used as part of an immunosuppressive protocol for renal Mycophenolate mofetil is a prodrug of mycophenolic acid
transplantation but is now also used as adjunctive treatment (MPA), an inhibitor of the enzyme inosine monophosphate
in dogs that are refractory to more traditional immuno- dehydrogenase (IMPDH) required for purine synthesis.
suppressive drugs and in patients in which glucocorticoids MPA inhibits proliferation of B and T cells and decreases
are contraindicated. Published studies regarding leflun- antibody production. Mycophenolate mofetil was developed
omide use in dogs are limited, but a retrospective study as an alternative to azathioprine due to its similar mecha-
reporting its use as a monotherapy for immune-mediated nism of action and low risk of myelotoxicity. Mycophenolate
polyarthritis in dogs was encouraging. Leflunomide has has most commonly been used in transplantation medicine
also been used for treatment of Evans syndrome, IMHA, for prevention of rejection; however, it has become widely
and polymyositis. used in clinical veterinary medicine for immunosuppres-
Adverse effects are uncommon but include decreased sion, particularly for treatment of IMHA and ITP. Mycophe-
appetite, lethargy, mild anemia, and hematemesis or hema- nolate has also been used in refractory cases of mysathenia
tochezia when used in conjunction with corticosteroids. An gravis, inflammatory bowel disease, and meningoencephalo-
idiosyncratic thrombotic microangiopathy is also described myelitis of unknown etiology.
in dogs but is reversible with discontinuation of the drug. Advantages of mycophenolate include its availability
The current recommended dose is 2 to 4 mg/kg PO q24h. as both an oral and parenteral product, which is appeal-
Therapeutic monitoring for leflunomide is available through ing for anorectic patients. Other advantages include a
the Clinical Pharmacology Laboratory at Auburn Univer- low risk of toxicity. The most common adverse effects
sity (Clinical Pharmacology Laboratory, 1500 Wire Road, are gastrointestinal toxicity, which previously occurred in
142-A McAdory Hall, Auburn University, AL 36849; up to 67% of patients. Gastrointestinal toxicity, including
clinpharm@auburn.edu). hemorrhagic diarrhea, has the potential to be severe, but