Methotrexate with cyclosporine

What lab tests would be important to perform prior to starting therapy with methotrexate With cyclosporine ... 

Acitretin is an oral retinoid that is likely safer than methotrexate or cyclosporine, especially when considering continuous use over many years.21 The initial dose is 25 mg/day which can be increased to a maximum of 75 mg/day if needed.17 When acitretin is used concurrently with phototherapy (ReUVB or RePUVA), there appears to be a synergistic treatment effect, and the number and duration of phototherapy sessions needed to achieve clearance is reduced.21 RePUVA is a well-established... 

Methotrexate has been used successfully with cyclosporine, either concurrently34 or in rotation. Rotational therapy is particularly effective since it minimizes the serious adverse effects of both agents hepatotoxidty from methotrexate and hypertension and nephrotoxicity from cyclosporine. Having an overlapping treatment period may not be necessary and patients have been successfully switched after a 1-week washout period.21,35 This is a very useful combination of systemic agents in the longterm management of this chronic disease. 

It was decided to begin methotrexate in this patient, rotating with cyclosporine. 

Clinically important, potentially hazardous interactions with cyclosporine, lithium, methotrexate, mifepristone, NSAIDs, quinolones, salicylates... 

Immunosuppressive drugs Azathioprine, steroids, methotrexate, macrolides (Cyclosporin A, Tacrolimus, i.e., FK506 or fujimycin, Rapamycin), deoxyspergualin Association with risk of clinical infections clearly established. Organ transplant patients are known to develop more malignancies... 

Chao NJ, Schmidt GM, Niland JC, et al. Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone alone for the prophylaxis of acute graft-versus-host disease. N Engl J Med 1993 329 1225-1230. 

Ruutu T, Volin L, Parkkli T, et al. Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor A prospective randomized study. Blood 2000 96 2391-2398. 

Ratanatharathorn V, Nash RA, Przepiorka D, et al. Phase III study comparing methotrexate and tacrolimus (Prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after... 

Nash, R. A., Antin, J. H., Karanes, C., Fay, J. W., Avalos, B. R., Yeager, A. M., Przepiorka, D., Davies, S., Petersen, F. B., Bartels, R, Buell, D., Fitzsimmons, W., Anasetti, C., Storb, R, and Ratanatharathom, V. (2000). Phase III study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood 96(6), 2062-2068. 

The resolution of acute lupus pneumonitis often occurs quickly once immunosuppressives have been initiated. Corticosteroids in high dose are indicated, although cases of relapse on corticosteroid monotherapy have been seen (29). Therefore, the usual patient will be started on adjunctive immunosuppressives dictated by the extent of multiorgan involvement and the confidence that infection has been excluded or adequately treated. Experience with aza-thioprine, methotrexate, cyclophosphamide, cyclosporine, and mycophenalate mofetil has been reported. 

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

The combination of cyclosporine with calcipotriol may be more efficacious than either agent used alone.21,37 Cyclosporine and SCAT may also be effective.21,38 However, cyclosporine should not be used concurrently with PIJVA there is a well-documented increased risk of squamous cell cancer and the combination may have a negative effect on lesion clearance.21 The combination of cyclosporine with methotrexate is extremely effective and minimizes toxicity from either agent as discussed. Cyclosporine has also been used successfully with mycophenolate mofetil38 and etanercept.29... 

Drugs that may interact with sulfasalazine include digoxin, sulfonylureas, folic acid, cyclosporine, methotrexate, thiopurines, and warfarin. 

Drugs that may interact with sulfonamides include oral anticoagulants, cyclosporine, hydantoins, methotrexate, and sulfonylureas. 

Hypersensitivity to polyoxyethylated castor oil (injection only see Warnings and Administration and Dosage), cyclosporine, or any component of the products Gengraf and Neoral in psoriasis or RA patients with abnormal renal function, uncontrolled hypertension, or malignancies Gengraf and A/eora/concomitantly with PUVA or DVB, methotrexate or other immunosuppressive agents, coal tar or radiation therapy in psoriasis patients. 

For immunosuppressive effects methotrexate is most frequently used in RA but also azathioprine and cyclosporin are employed. Methotrexate doses for this indication can be lower than those used for cancer chemotherapy but significant toxicity such as nausea, cytopenias and mucosal lesions, and with longterm therapy slowly progressive hepatotoxicity may still be seen. 

The principal advantage of MMF over alternative systemic immunosuppressive agents (e.g., methotrexate, cyclosporine) is its relative lack of hepatotoxicity and nephrotoxicity. Adverse effects produced by MMF most commonly include nausea, abdominal cramps, diarrhea, and possibly an increased incidence of viral and bacterial infections. Whether MMF may be associated with an increased long-term risk of lymphoma or other malignancies is controversial however, any such risk is likely to be lower in patients treated for skin disease with MMF monotherapy than in transplant patients treated with combination immunosuppressive therapy. 

Trimethoprim has been reported to decrease the therapeutic effect of cyclosporine with a concomitant increased risk of nephrotoxicity. Increased levels of dapsone, warfarin, methotrexate, zidovudine, and sul-fonylureas may occur when given together with trimethoprim dosages of these drugs should be modified and the patient monitored accordingly. 

When added to methotrexate background therapy, cyclosporine, chloroquine, hydroxychloroquine, leflunomide, infliximab, adalimumab, rituximab, and etanercept have all shown improved efficacy. In contrast, azathioprine, auranofin, or sulfasalazine plus methotrexate results in no additional therapeutic benefit. Other combinations have occasionally been used, including the combination of intramuscular gold with hydroxychloroquine. 

Gerards AH et al Cyclosporine A monotherapy versus cyclosporine A and methotrexate combination therapy in patients with early rheumatoid arthritis A double blind randomised placebo controlled trial. Ann Rheum Dis 2003 62 291. [PMID 12634224]... 

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

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