Mycophenolate Mofetil
**Mycophenolate mofetil (MMF)** is a potent **immunosuppressant** drug increasingly utilized in veterinary medicine as a steroid-sparing agent or rescue therapy for severe, refractory immune-mediated diseases. Key clinical applications include: * **Immune-mediated hemolytic anemia (IMHA)** * **Glomerulonephritis** * **Myasthenia gravis** * **Pemphigus foliaceous** * Organ transplant anti-rejection protocols While it has been suggested for inflammatory bowel disease (IBD), its use is complicated because the drug's primary adverse effects in dogs are gastrointestinal (gastritis, diarrhea, and intestinal inflammation). **Clinical Pearl:** MMF is often preferred over azathioprine in some critical cases due to its relatively rapid onset of action, but its high cost and severe GI side effects can be limiting factors. Experience in cats is very limited, and it must be used with extreme caution due to feline deficiencies in glucuronidation pathways.
Mecanismo: **Mycophenolate mofetil (MMF)** is a prodrug that is rapidly hydrolyzed *in vivo* to its active form, **mycophenolic acid (MPA)**. * MPA non-competitively and reversibly inhibits **inosine monophosphate dehydrogenase (IMPDH)**. * **IMPDH** is the rate-limiting enzyme in the *de novo* synthesis of guanosine nucleotides. * Because T-lymphocytes and B-lymphocytes are highly dependent on this *de novo* purine synthesis pathway (and lack the purine salvage pathways utilized by other cell types), MPA selectively inhibits their proliferative responses. * This leads to → suppression of B-cell antibody formation and → inhibition of leukocyte recruitment to inflammatory sites and allotransplant tissues.
Dosificación por especie
- IMHA · 10 mg/kg PO q12h · PO · q12h · Use with caution due to feline glucuronidation deficiency.
- Immune-mediated hemolytic anemia (IMHA) · 12-17 mg/kg PO once daily or divided twice daily · PO · q12-24h · Given with prednisolone (at 2 mg/kg q12-24h). Dogs also received ranitidine and sucralfate in the study.
- IMHA, myasthenia gravis or glomerulonephritis · 12-17 mg/kg PO once daily or divided twice daily · PO · q12-24h · Given with prednisone (at 2.2 mg/kg q12-24h).
- Immune-mediated hemolytic anemia (IMHA) · 400-600 mg/m2 orally twice daily · PO · q12h · Extrapolated from human medicine. Gastrointestinal side effects are common and dose limiting.
- Adjunctive treatment of glomerulonephritis · 10-20 mg/kg PO q12h · PO · q12h · 3-4 weeks trial · Trial of single drug therapy for 3-4 weeks recommended.
- Pemphigus foliaceous · 22-39 mg/kg/day divided into 3 daily doses · PO · q8h · Success rates of approx 50%; most dogs require glucocorticoids to control signs.
- Pemphigus foliaceous · 20-40 mg/kg/day PO divided q8h · PO · q8h · Steroid-sparing only.
- Aplastic anemia · 10 mg/kg PO q12h · PO · q12h · First effects observed 2 weeks later; complete remission in approx 3 weeks.
- Rescue agent for generalized myasthenia gravis · 500 mg (15-20 mg/kg) diluted and given IV over 2-4 hours · IV · q24h · 13 days · Given daily IV until swallowing oral meds, then switched to 10-11 mg/kg PO q12h.
Vías de administración
Contraindicaciones
- Documented hypersensitivity to mycophenolate
- Pregnancy (teratogenic effects noted in animal models)
- Caution in patients with severe renal dysfunction (dosage adjustment may be required)
- Caution in cats (deficient in glucuronidation metabolism)
- Pre-existing bone marrow suppression
- Pre-existing infections
Efectos adversos
- Diarrhea (can be severe)
- Vomiting
- Anorexia
- Lethargy / reduced activity
- Weight loss
- Lymphopenia
- Increased rates of dermal infections
- Increased susceptibility to systemic infections
- Potential increased risk of malignancy/lymphoma
- Bone marrow suppression
- Nausea
- Diarrhoea
- Increased incidence of infections (e.g., pyoderma, Malassezia)
- Increased risk of lymphoma (reported in humans)
- Headache (reported in humans)
- Hypertension (reported in humans)
Interacciones farmacológicas
- Acyclovir · Increased serum concentrations of acyclovir and the phenolic glucuronide of mycophenolic acid
- Antacids (aluminum or magnesium containing) · Decreased absorption of mycophenolate; separate dosing by at least 2 hours
- Aspirin (or other salicylates) · Potentially increased concentrations of free mycophenolic acid
- Azathioprine · Increased risk for bone marrow suppression; use together not recommended in humans
- Iron (oral) · Decreased absorption of mycophenolate; separate dosing by at least 2 hours
- Probenecid · Potentially increased serum levels of mycophenolic acid and the phenolic glucuronide of mycophenolic acid
- Vaccines (live virus) · May be less effective; avoid use
- Drugs undergoing active renal tubular secretion · Competes for secretion, resulting in increased concentrations of either drug · moderate
- Antacids (e.g., omeprazole) · Concomitant administration may decrease the absorption of mycophenolate · moderate
Monitorización
- Clinical efficacy (resolution of immune-mediated disease signs)
- Complete Blood Count (CBC) for bone marrow suppression
- Renal and hepatic function panels
- Serum electrolytes
- Gastrointestinal effects (monitor weight, appetite, and client reports of vomiting/diarrhea)
- Complete Blood Count (CBC) to monitor for bone marrow suppression
- Gastrointestinal signs (nausea, vomiting, diarrhea)
- Signs of secondary infections (e.g., skin lesions, lethargy, fever)
Sobredosis
In oral acute studies performed in mice and monkeys, no deaths occurred in dosages up to 4,000 mg/kg and 1,000 mg/kg, respectively. In small animals, acute gastrointestinal disturbances (severe vomiting, diarrhea) could be expected. Treatment should be symptomatic and supportive.
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