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Myfortic® (mycophenolate sodium) delayed-release tablets

  • Author(s): Qureshi, Ansa
  • Scheinfeld, Noah
  • et al.
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Myfortic® (mycophenolate sodium) delayed-release tablets
Ansa Qureshi, Noah Scheinfeld
Dermatology Online Journal 14 (8): 4

Assistant Clinical Professor of Dermatology, Department of Dermatology, Columbia University, New York, NY. NSS32@columbia.edu

Abstract

Myfortic® is a new formulation of mycophenolic acid (MPA) utilizing enteric coated mycophenolate sodium (EC-MPS) that may have fewer gastrointestinal side effects.


Mycophenolate sodium (MPS) is a salt that combines an acid-MPA with a base-sodium. The enteric coating delays MPS's release so that the EC-MPS is absorbed in the small intestine [1-12].

Mycophenolic acid is an uncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH). Mycophenolic acid inhibits IMPDH, needed for the functioning of the de novo pathway of guanosine (purine) nucleotide synthesis and crucial for lymphocyte proliferation [1]. Thus, MPA mostly effects activated lymphocytes rather than inactive lymphocytes. The apparently low hepatotoxicity, nephrotoxicity, and carcinogenicity of MMF have made it a useful therapeutic agent.

The MPA molecule and its variants have been utilized for decades. Introduced in the 1970s as a treatment for psoriasis, mycophenolic acid was reformulated as mycophenolate mofetil (MMF) (brand name Cellcept®) [7]. Mycophenolate mofetil, prednisone, and cyclosporine or tacrolimus are FDA approved for combination use to prevent the rejection of renal allografts [1].

The administration of MMF sometimes results in dose-limiting GI side effects. EC-MPS was formulated in an attempt to decrease the GI upset of MPA [2].

After oral administration, MMF is rapidly converted to MPA. Studies show that unlike MMF, EC-MPS does not release MPA under acidic conditions such as those found in the stomach. Whereas after administration of MMF, median time to maximal concentration was 0.5 to 1.0 hours, the Tmax of MPA after EC-MPS was 1.5 to 2.75 hours, consistent with delayed absorption that occurs in the small intestines [1].

Enteric coated mycophenolate sodium 720 mg twice-a-day has been found to be therapeutically equivalent to MMF 1000 mg twice-a-day. Several studies have confirmed that EC-MPS and MMF have similar efficacy. Although several studies have found that EC-MPS and MMF have similar adverse event profiles, including similar incidence of GI side effects, other studies have shown a better GI side effect profile with EC-MPS [2, 3, 4]. Switching from MMF to EC-MPS in patients with GI side effects may be beneficial. Several studies have shown that GI symptoms improved in transplant patients switched from MMF to EC-MPS [5]. In a study by Chan et al. patients with GI complaints who were switched from MMF to EC-MPS had significant improvement on scales measuring GI symptoms and quality of life [6].

Enteric coated mycophenolate sodium is currently indicated for use in the prophylaxis of organ rejection in patients with kidney transplants, given in combination with cyclosporine and corticosteroids. It is likely to find a place in the treatment of lupus nephritis, pemphigus, and other dermatological diseases. Studies have already shown that EC-MPS may be helpful in ocular cicatricial pemphigoid, uveitis [8], and Sjogren's syndrome [9]. Enteric coated mycophenolate sodium has also been studied as a treament for lupus erythematosus and bullous diseases [10, 11, 12].

Kreuter et al. performed a prospective, nonrandomized, open pilot study of ten patients to evaluate efficacy of EC-MPS in patients with recalcitrant subacute cutaneous lupus erythematosus. Patients received 1440 mg daily for 3 months as monotherapy. There was a significant decrease on the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) from 10.8 +/- 6.0 to 2.9 +/- 2.6 at the end of treatment. Ultrasonography and colorimetry confirmed improvement and no serious side effects were noted [10].

Marzano et al. studied the use of MPA in 12 patients with various blistering diseases. Of these, ten patients received steroids in addition to MPA and two received MPA monotherapy (four patients received MMF, seven received EC-MPS, and patient received both sequentially). The duration of MPA treatment was 2-8 months. Out of the twelve patients, ten achieved complete remission and two achieved partial remission. Whereas both MMF and EC-MPS were well tolerated, EC-MPS was better tolerated in terms of GI side effects [11].

Enteric coated mycophenolate sodium is contraindicated in patients with hypersensitivity to mycophenolate sodium, mycophenolic acid, or mycophenolate mofetil. In addition, it is pregnancy category D (MMF and EC-MPS had been pregnancy category C until recently) and has been associated with increased risk of pregnancy loss and congenital malformations. It should also be avoided in patients with the rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) as seen in the Lesch-Nyhan or Kelley-Seegmiller syndrome [1].

Patients treated with immunosuppressive regimens are at increased risk of lymphoma and other malignancies, especially skin cancer. Patients receiving immunosuppressants may also be at increased risk of infection. Patients should be monitored for neutropenia.

Myfortic® is supplied as 180 mg and 360 mg tablets. The recommended dose is 720 mg twice-a-day on an empty stomach. Tablets should be swallowed whole.

Although more studies are needed, EC-MPS is a newer formulation of MPA that may have better GI tolerability and has the potential to be useful as an immunosuppressant and steroid-sparing agent in many dermatologic and connective tissue diseases.

References

1. Myfortic [package insert]. East Hanover, NJ: Novartis Pharmaceuticals; 2007.

2. Johnston A, He X, Holt DW. Bioequivalence of enteric-coated mycophenolate sodium and mycophenolate mofetil: a meta-analysis of three studies in stable renal transplant rEC-MPSipients. Transplantation. 2006;82:1413-8. PubMed

3. Salvadori M, Holzer H, Civati G, Sollinger H, Lien B, Tomlanovich S, Bertoni E, Seifu Y, Marrast AC; ERL B301 Study Group. Long-term administration of enteric-coated mycophenolate sodium (EC-MPS; myfortic) is safe in kidney transplant patients. Clin Nephrol. 2006;66:112-9. PubMed

4. Budde K, Knoll G, Curtis J, Chan L, Pohanka E, Gentil M, Seifu Y, Marrast AC, Neumayer HH; ERL B302 Study Group. Long-term safety and efficacy after conversion of maintenance renal transplant recipients from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS, myfortic). Clin Nephrol. 2006;66:103-11. PubMed

5. Calvo N, Sanchez-Fructuoso AI, Conesa J, Moreno A, Barrientos A. Renal transplant patients with gastrointestinal intolerability to mycophenolate mofetil: conversion to enteric-coated mycophenolate sodium. Transplant Proc. 2006;38:2396-7. PubMed

6. Chan L, Mulgaonkar S, Walker R, Arns W, Ambühl P, Schiavelli R. Patient-reported gastrointestinal symptom burden and health-related quality of life following conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium. Transplantation. 2006;81:1290-7. PubMed

7. Mydlarski PR. Mycophenolate mofetil: a dermatologic perspective. Skin Therapy Lett. 2005;10:1-6. PubMed

8. Pleyer U, Ruokonen P, Schmidt N, Feist E, Höhne M, Stanojlovic S. Ein Beitrag zur Anwendung von Mycophenolsäure bei Autoimmunerkrankungen des Auges: Können wir die Therapie optimieren? Mycophenol Acid in Ocular Automimmune Disorders - Can We Optimise this Therapy? Klin Monatsbl Augenheilkd. 2008;225:66-9. PubMed

9. Willeke P, Schlüter B, Becker H, Schotte H, Domschke W, Gaubitz M. Mycophenolate sodium treatment in patients with primary Sjögren syndrome: a pilot trial. Arthritis Res Ther. 2007;9:R115. PubMed

10. Kreuter A, Tomi NS, Weiner SM, Huger M, Altmeyer P, Gambichler T. Mycophenolate sodium for subacute cutaneous lupus erythematosus resistant to standard therapy. Br J Dermatol. 2007;156:1321-7. PubMed

11. Marzano AV, Dassoni F, Caputo R. Treatment of refractory blistering autoimmune diseases with mycophenolic acid. J Dermatolog Treat. 2006;17:370-6. PubMed

12. Tursen U, Guney A, Kaya T, Ikizoglu G. Treatment of bullous pemphigoid with enteric-coated mycophenolate sodium. J Eur Acad Dermatol Venereol. 2007;21:542-4. PubMed

© 2008 Dermatology Online Journal