Table VIII. Adverse effects, interactions and contraindication of selected systemic immunomodulatory agents.

Drug	Potential Toxicities	Interactions	Contraindications
Cyclosporine	Pregnancy category C Renal impairment Hypertension Headache, tremor, paresthesia Hypertrichosis Gingival hyperplasia Nausea/vomiting/diarrhea Flu-like symptoms -Myalgias, Lethargy Hypertriglyceridemia Hypomagnesemia Hyperkalemia Hyperbilirubinemia Increased risk of infection Risk of malignancies -Cutaneous -Lymphoproliferative	Medications that increase cyclosporine levels -Antifungals: ketoconazole, itraconazole, fluconazole, vorinconazole -Diuretics: furosemide, thiazides, carbonic anhydrase inhibitors -Calcium channel antagonists: diltiazem, nicardipine, verapamil -Corticosteroids: high-dose methylprednisolone -Antiemetics: metoclopramide -Antibiotics: macrolides, fluoroquinolones -Antiarrhythmics: amiodarone -Antimalarials: hydroxychloquine, chloroquine -Anti-HIV drugs: ritonavir, indinavir, saquinavir, nelfinavir -SSRIs: fluoxetine, sertraline Medications that decrease cyclosporine levels -Antibiotics: nafcillin, rifabutin, rifampin, rifapentine -Antiepileptics: carbamazepine, phenytoin, phenobarbital, valproic acid -Somatostatin analogues: octreotide -Tuberculostatics: rifampicin -Retinoids: bexarotene -St. John wort: Hypericum perforatum -Others: octreotide, ticlopidine, bosentan Medications that may increase risk of renal toxicity -NSAIDs: diclofenac, naproxen, sulindac, indomethacin -Antifungals: amphotericin-B, ketoconazole -Antibiotics: ciprofloxacin, vancomycin, gentamycin, tobramycin, trimethoprim -Alkylating agents: melphalan -Others: H2 histamine antagonists, tacrolimus Medications whose levels increase if taken with cyclosporine -Calcium channel blockers: diltiazem, nicardipine, verapimil -Erectile dysfunction drugs: sildenafil, tadalafil, vardenafil -Statins: atorvastatin, lovastatin, simvastatin -Benzodiazepines: midazolam, triazolam -Others: prednisolone, digoxin, colchicine, digoxin, diclofenac, bosentan	Caution Concomitant PUVA or UVB History of significant PUVA or radiation Concomitant methotrexate or other immunosuppressive agents Coal tar Major infection Poorly controlled diabetes Absolute Abnormal renal function Uncontrolled hypertension Malignancy Hypersensitivity to cyclosporine Killed vaccines may have decreased efficacy Live vaccines may be contraindicated*
Azathioprine	Pregnancy category D Bone-marrow suppression Increased risk of infections Nausea, vomiting, diarrhea Hypersensitivity syndrome Pancreatitis Hepatitis Risk of malignancies -Cutaneous -Lymphoproliferative	-Allopurinol increases risk of pancytopenia, must reduce azathioprine dose by 75% -Captopril increases risk of anemia and leukopenia -Warfarin effect is reduced - Pancuronium effect is reduced -Cotrimoxazole increases risk of hematologic toxicity -Rifampicin decreases azathioprine efficacy; hepatotoxic -Clozapine increases risk of agranulocytosis	Absolute Allergy to azathioprine Pregnancy or attempting pregnancy Clinically significant active infection Relative Concurrent use of allopurinol Prior treatment with cyclophosphamide or chlorambucil Live vaccines may be contraindicated*
Methotrexate	Pregnancy category X Elevated liver enzymes Cytopenias Interstitial pneumonitis Pulmonary fibrosis Ulcerative stomatitis Nausea, vomiting, diarrhea Malaise, fatigue Chills and fever Dizziness Risk of infection GI ulceration and bleeding Photosensitivity Alopecia Risk of malignancies -Cutaneous -Lymphoproliferative	Hepatotoxic drugs: eg, barbiturates Sulfamethoxazole, NSAIDs, and penicillins (interfere with renal secretion of MTX) Folic acid antagonists: eg, trimethoprim	Absolute Pregnancy Nursing mothers Alcoholism Alcoholic liver disease Chronic liver disease Immunodeficiency Bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia Hypersensitivity to methotrexate Relative Abnormalities in renal function Abnormalities in liver function Active infection Obesity Diabetes mellitus Live vaccines may be contraindicated*
Mycophenolate mofetil	Pregnancy category D GI most common -diarrhea, nausea, vomiting, abdominal cramps Hematologic -leukopenia, anemia, thrombocytopenia Genitourinary -urgency, frequency, dysuria, sterile pyuria Increased incidence of infections Progressive multifocal leukoencephalopathy Hypercholesterolemia Hypophosphatemia Hyperkalemia Hypokalemia Fever, headache, mylagias Insomnia Peripheral edema Hypertension Risk of malignancies -Cutaneous -Lymphoproliferative	Antacids containing aluminum and magnesium Calcium and iron Cholestyramine Antibiotics (cephalosporins, fluoroquinolones, macrolides, penems, penicillins, sulfonamides) decrease MMF levels High-dose salicylates Phenytoin Xanthine bronchodilators Probenecid Acyclovir, ganciclovir, valganciclovir	Hypersensitivity to MMF and mycophenolic acid Live vaccines may be contraindicated* Pregnancy or attempting pregnancy

MTX, methotrexate; NSAIDS, nonsteroidal anti-inflammatory drugs; HIV, human immunodeficiency virus; SSRI, selective serotonin reuptake inhibitor; PUVA, psoralen plus ultraviolet A; UVB, ultraviolet B; MMF, mycophenolate mofetil; GI, gastrointestinal.

Adapted from Journal of the American Academy of Dermatology, Volume 61,Menter, A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB et al, Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 4: Guidelines of care for the management and treatment of psoriasis with traditional systemic agents, pages 451-85, Copyright 2009, with permission from the American Academy of Dermatology.

^*Live vaccines may be contraindicated dependent upon medication, dose and the type of vaccine to be administered. Please reference up to date vaccine contraindication recommendations.