Mycophenolate Mofetil (Cellcept)

Indications

Transplantation

Other


Pharmacology

  • Inhibitor of Inosine Monophosphate Dehydrogenase (IMPDH): inhibits de novo guanosine nucleotide synthesis
    • Cytostatic Effect on Both T-Lymphocytes and B-Lymphocytes: since T/B-cells are dependent on this pathway for proliferation

Pharmacodynamics

  • Elimination Half-Life
    • Cellcept
      • PO: 18 hrs for MPA
      • IV: 17 hrs for MPA
    • Myfortic
      • PO: 8-16 hrs for MPA (13-17 hrs for MPAG)

Metabolism

  • Hepatic and Via Gastrointestinal Tract
    • Cellcept is completely hydrolyzed by the liver to mycophenolic acid (MPA), which is an active metabolite
    • Enterohepatic circulation of mycophenolic acid may occur
    • Mycophenolic acid is glucuronidated to MPAG (an inactive metabolite)

Administration

  • PO (Mycophenolate Mofetil = Cellcept)
    • Renal Transplant: 1 g BID
    • Cardiac Transplant: 1.5 g BID
    • Liver Transplant: 1.5 g BID
  • PO (Mycophenolic Acid = Myfortic)
    • Renal Transplant: 720 mg BID
  • IV (Mycophenolate Mofetil = Cellcept): limit use to max of 14 days
    • Renal Transplant: 1 g BID
    • Cardiac Transplant: 1.5 g BID
    • Liver Transplant: 1 g BID

Dose Adjustment

  • Hepatic: no dose adjustment required for renal patients with severe liver disease (unclear if dose adjustment is required in other settings with liver disease)
  • Renal
    • Renal Transplant
      • GFR <25 mL/min (Outside of Immediate Post-Transplant Period)
        • Cellcept: avoid doses >1 g
        • Myfortic: no dose adjustment required
    • Cardiac/Liver Transplant: no data available
    • Autoimmune Disease: no specific dose adjustment required (however, since mycophenolate exposure appears to be related to renal function, close monitoring in the setting of renal dysfunction, especially with end-stage renal disease, is recommended)
  • Hemodialysis: no dose adjustment required (as drug is not removed by hemodialysis)
  • Peritoneal Dialysis: no dose adjustment required

Pregnancy

  • Increased Risk of Congenital Malformations/First Trimester Pregnancy Loss

Adverse Effects

Cardiovascular Adverse Effects

  • Chest Pain (see Chest Pain, [[Chest Pain]]): occurs in 26% of cases
  • Hypertension (see Hypertension, [[Hypertension]]): occurs in 28-78% of cases
  • Hypotension (see Hypotension, [[Hypotension]]): occurs in 33% of cases
  • Sinus Tachycardia (see Sinus Tachycardia, [[Sinus Tachycardia]])): occurs in 20-22% of cases

Dermatologic Adverse Effects

  • Rash: occurs in 22% of case

Endocrinologic Adverse Effects

  • Hyperglycemia (see Hyperglycemia, [[Hyperglycemia]])): occurs in 44-47% of cases
  • Hyperlipidemia (see Hyperlipidemia, [[Hyperlipidemia]]): occurs in 41% of cases

Gastrointestinal Adverse Effects

  • Diarrhea (see Diarrhea, [[Diarrhea]]): occurs in 31-51% of cases
  • Elevated Liver Function Tests (LFT’s) (see Drug-Induced Hepatotoxicity, [[Drug-Induced Hepatotoxicity]]): occurs in 25% of cases
  • Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]]): occurs in 33% of cases

Hematologic Adverse Effects

Anemia/Pure Red Cell Aplasia (see Anemia, [[Anemia]])

  • Epidemiology: occurs in 26-43% of cases

Increased Risk of Malignancy

  • Post-Transplant Lymphoproliferative Disease
  • Skin Cancer

Leukopenia/Neutropenia (see Leukopenia, [[Leukopenia]])

  • Epidemiology: leukopenia occurs in 23-46% of cases
  • Physiology: xxx
  • Management: may require interruption or reduction of dosing

Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])

  • Epidemiology: occurs in 24-38% of cases

Immunologic Adverse Effects

Hypogammaglobulinemia (see Hypogammaglobulinemia, [[Hypogammaglobulinemia]])

  • Epidemiology
  • Clinical

Infectious Adverse Effects

  • Bacterial
    • Atypical Mycobacteria
    • Tuberculosis (see Tuberculosis, [[Tuberculosis]])
  • Fungal
  • Protozoal
  • Viral
    • BK Virus-Related Polyoma Virus-Associated Nephropathy (PVAN) (see BK Virus, [[BK Virus]])
    • Cytomegalovirus (CMV) (see Cytomegalovirus, [[Cytomegalovirus]])
    • Hepatitis B Virus Reactivation (see Hepatitis B Virus, [[Hepatitis C Virus]])
    • Hepatitis C Virus Reactivation (see Hepatitis C Virus, [[Hepatitis C Virus]])
    • JC Virus-Associated Progressive Multifocal Leukoencephalopathy (see JC Virus, [[JC Virus]]): occurs in <1% of cases

Neurologic Adverse Effects

  • Headache (see Headache, [[Headache]]): occurs in 16-54% of cases
  • Parasthesias (see Parasthesias, [[Parasthesias]]): occur in 21% of cases
  • Tremor (see Tremor, [[Tremor]]): occurs in 24-34% of cases

Pulmonary Adverse Effects

Bronchiectasis (see Bronchiectasis, [[Bronchiectasis]]): occurs in <1% of cases

  • Epidemiology: case reports
  • Physiology: may be related to hypogammaglobulinemia

Cough (see Cough, [[Cough]])

  • Epidemiology: case reports
  • Clinical: dry cough

Diffuse Alveolar Hemorrhage (DAH) with Capillaritis (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]])

  • Epidemiology: case reports

Interstitial Lung Disease (ILD) (see Interstitial Lung Disease, [[Interstitial Lung Disease]])

  • Epidemiology: occurs in <1% of cases

Renal Adverse Effests

Rheumatologic Adverse Effects

Other Adverse Effects

  • Fever (see Fever, [[Fever]])

References

  • Mycophenolate mofetil and cough. Transplantation. 1998 Aug 15;66(3):409 [MEDLINE]
  • Mycophenolate mofetil and bronchiectasis in kidney transplant patients: a possible relationship. Transplantation. 2006 Jan 27;81(2):287-9 [MEDLINE]
  • Hypogammaglobulinemia and bronchiectasis in mycophenolate mofetil-treated renal transplant recipients: an emerging clinical phenomenon? Clin Transplant. 2011 May-Jun;25(3):417-9. doi: 10.1111/j.1399-0012.2010.01255.x. Epub 2010 Apr 21 [MEDLINE]
  • Pulmonary hemorrhage with capillaritis secondary to mycophenolate mofetil in a heart-transplant patient. Arch Pathol Lab Med. 2013 Nov;137(11):1684-7. doi: 10.5858/arpa.2012-0460-CR [MEDLINE]
  • Mycophenolate-associated bronchiectasis. Respiration. 2014;88(1):86. doi: 10.1159/000360299. Epub 2014 Apr 25 [MEDLINE]
  • Bronchiectasis diagnosed after renal transplantation: a retrospective multicenter study. BMC Pulm Med. 2015 Nov 7;15:141. doi: 10.1186/s12890-015-0133-9 [MEDLINE]