Neurol. praxi. 2017;18(5):309-313 | DOI: 10.36290/neu.2017.103

Challenges of ciclosporin and azathioprin dosage for myasthenia gravis

MUDr. Magda Horáková, MUDr. Stanislav Voháňka, CSc., MBA
Neurologická klinika FN a LF MU, Brno

Azathioprin (Imuran) and ciclosporin (Sandimmun Neoral, Equoral) are among the most widely used immunosuppressive drugsfor myasthenia gravis. They are very efficient and help to improve patient’s quality of life. However, such therapy has some risks. Atleast part of the risks can be avoided by managing the right dose, which requires certain experience. The aim of this article is a reviewof their side effects, metabolic pathways and interactions, therapeutic drug monitoring and some dosage recommendations.

Keywords: azathioprin, ciclosporin, cyclosporin, neoral, therapeutic drug monitoring

Published: November 1, 2017  Show citation

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Horáková M, Voháňka S. Challenges of ciclosporin and azathioprin dosage for myasthenia gravis. Neurol. praxi. 2017;18(5):309-313. doi: 10.36290/neu.2017.103.
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    References

    1. Calne RY. Inhibition of the rejection of renal homografts in dogs by purine analogues. Transplant. Bull. 1961; 28: 65-81. Go to original source... Go to PubMed...
    2. Christians U, Strom T, Zhang YL, Steudel W, Schmitz V, Trump S, Haschke M. Active drug transport of immunosuppressants: new insights for pharmacokinetics and pharmacodynamics. Ther. Drug Monit. 2006; 28: 39-44. Go to original source... Go to PubMed...
    3. Dalakas MC. Polymyositis and Dermatomyositis. Butterworth-Heinemann; 2013.
    4. David OJ, Johnston A. Limited sampling strategies for estimating cyclosporin area under the concentration-time curve: review of current algorithms. Ther. Drug Monit. 2001; 23: 100-114. Go to original source... Go to PubMed...
    5. Dubinsky MC, Lamothe S, Yang HY, Targan SR, Sinnett D, Théor?t Y, Seidman EG. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000; 118: 705-713. Go to original source... Go to PubMed...
    6. Feutren G, Mihatsch MJ. Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. International Kidney Biopsy Registry of Cyclosporine in Autoimmune Diseases. N. Engl. J. Med. 1992; 326: 1654-1660. Go to original source... Go to PubMed...
    7. Heerasing NM, Ng JF, Dowling D. Does lymphopenia or macrocytosis reflect 6-thioguanine levels in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine? Intern. Med. J. 2015: n/a-n/a. Go to original source... Go to PubMed...
    8. Hitchings GH, Elion GB. The chemistry and biochemistry of purine analogs. Ann. N. Y. Acad. Sci. 1954; 60: 195-199. Go to original source... Go to PubMed...
    9. Italia JL, Bhardwaj V, Ravi Kumar MNV. Disease, destination, dose and delivery aspects of ciclosporin: the state of the art. Drug Discov. Today 2006; 11: 846-854. Go to original source... Go to PubMed...
    10. Kopylov U, Battat R, Benmassaoud A, Paradis-Surprenant L, Seidman EG. Hematologic indices as surrogate markers for monitoring thiopurine therapy in IBD. Dig. Dis. Sci. 2015; 60: 478-484. Go to original source... Go to PubMed...
    11. Lennard L, Lilleyman JS. Individualizing therapy with 6-mercaptopurine and 6-thioguanine related to the thiopurine methyltransferase genetic polymorphism. Ther. Drug Monit. 1996; 18: 328-334. Go to original source... Go to PubMed...
    12. Lill J, Bauer LA, Horn JR, Hansten PD. Cyclosporine-drug interactions and the influence of patient age. Am. J. Health-Syst. Pharm. AJHP Off. J. Am. Soc. Health-Syst. Pharm. 2000; 57: 1579-1584. Go to original source... Go to PubMed...
    13. Mertens HG, Balzereit F, Leipert M. The treatment of severe myasthenia gravis with immunosuppressive agents. Eur. Neurol. 1969; 2: 321-339. Go to original source... Go to PubMed...
    14. Nagane, Suzuki S, Suzuki N, Utsugisawa K. Factors associated with response to calcineurin inhibitors in myasthenia gravis. Muscle Nerve 2010; 41: 212-218. Go to original source...
    15. Nagane, Suzuki S, Suzuki N, Utsugisawa K. Two-year treatment with cyclosporine microemulsion for responder myasthenia gravis patients. Eur. Neurol. 2010; 64: 186-190. Go to original source... Go to PubMed...
    16. Ng HJ, Crowther MA. Azathioprine and inhibition of the anticoagulant effect of warfarin: evidence from a case report and a literature review. Am. J. Geriatr. Pharmacother. 2006; 4: 75-77. Go to original source... Go to PubMed...
    17. Osterman MT, Kundu R, Lichtenstein GR, Lewis JD. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology 2006; 130: 1047-1053. Go to original source... Go to PubMed...
    18. Ruschitzka F, Meier PJ, Turina M, Lüscher TF, Noll G. Acute heart transplant rejection due to Saint John's wort. Lancet Lond. Engl. 2000; 355: 548-549. Go to original source... Go to PubMed...
    19. Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, Kuntz N, Massey JM, Melms A, Murai H, Nicolle M, Palace J, Richman DP, Verschuuren J, Narayanaswami P. International consensus guidance for management of myasthenia gravis. Neurology 2016; 87: 419-425. Go to original source... Go to PubMed...
    20. Schumacher A, Nordheim A. Progress towards a molecular understanding of cyclosporin A-mediated immunosuppression. Clin. Investig. 1992; 70: 773-779. Go to original source... Go to PubMed...
    21. Simpson JA. Myasthenia gravis: a new hypothesis. Scott. Med. J. 1960; 5: 419-436. Go to original source...
    22. Smith MA, Marinaki AM, Arenas M, Shobowale-Bakre M, Lewis CM, Ansari A, Duley J, Sanderson JD. Novel pharmacogenetic markers for treatment outcome in azathioprine-treated inflammatory bowel disease. Aliment. Pharmacol. Ther. 2009; 30: 375-384. Go to original source... Go to PubMed...
    23. Strauss AJL, Seegal BC, Hsu KC, Burkholder PM, Nastuk WL, Osserman KE. Immunofluorescence Demonstration of a muscle binding, complement-fixing serum globulin fraction in myasthenia gravis. Exp. Biol. Med. 1960; 105: 184-191. Go to original source...
    24. Tiede I, Fritz G, Strand S, Poppe D, Dvorsky R, Strand D, Poppe D, Dvorsky R, Strand D, Poppe D, Dvorsky R, Strand D, Lehr HA, Wirtz S, Becker C, Atreya R, Mudter J, Hildner K, Bartsch B, Holtmann M, Blumberg R, Walczak H, Iven H, Galle PR, Ahmadian MR, Neurath M. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J. Clin. Invest. 2003; 111: 1133-1145. Go to original source... Go to PubMed...
    25. Tindall RS, Rollins JA, Phillips JT, Greenlee RG, Wells L, Belendiuk G. Preliminary results of a double-blind, randomized, placebo-controlled trial of cyclosporine in myasthenia gravis. N. Engl. J. Med. 1987; 316: 719-724. Go to original source... Go to PubMed...
    26. Torda C, Wolff HG. Effects of adrenocorticotrophic hormone on neuro-muscular function in patients with myasthenia gravis. J. Clin. Invest. 1949; 28: 1228-1235. Go to original source... Go to PubMed...
    27. Utsugisawa K, Nagane Y, Suzuki S, Suzuki N. Monitoring treatment with cyclosporine microemulsion in myasthenia gravis. Eur. J. Neurol. 2008; 15: 598-604. Go to original source... Go to PubMed...
    28. Walker MB. Treatment of myasthenia gravis with physostigmine. The Lancet 1934; 223: 1200-1201. Go to original source...
    29. Wolf SM, Rowland LP, Schotland DL, McKinney AS, Hoefer PFA, Aranow H. Myasthenia as an autoimmune disease: clinical aspects. Ann. N. Y. Acad. Sci. 1966; 135: 517-535. Go to original source... Go to PubMed...
    30. Zimm S, Collins JM, O'Neill D, Chabner BA, Poplack DG. Inhibition of first-pass metabolism in cancer chemotherapy: interaction of 6-mercaptopurine and allopurinol. Clin. Pharmacol. Ther. 1983; 34: 810-817. Go to original source... Go to PubMed...

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