Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

Abstract

Objectives: Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and infl ammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods: Committee members developed and refi ned a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions: It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease. CHEST 2012; 142(5):e1S-e111SAbbreviations: ACCP 5 American College of Chest Physicians; ALT 5 alanine aminotransferase; ATG 5 antithymocyte globulin; CHF 5 congestive heart failure; CMV 5 cytomegalovirus; CNI 5 calcineurin inhibitor; COI 5 confl ict of interest; CsA 5 cyclosporin A; FDA 5 US Food and Drug Administration; HBV 5 hepatitis B virus; HMG-CoA 5 b -hydroxy-bmethylglutaryl-coenzyme A; HSP 5 Health and Science Policy Committee; IL2RA 5 IL-2 receptor a ; ILD 5 interstitial lung disease; IPF 5 idiopathic pulmonary fi brosis; ITP 5 idiopathic thrombocytopenia purpura; LAM 5 lymphangioleiomyomatosis; MESNA 5 sodium 2-sulfonylethanesufonate; MPA 5 mycophenolic acid; mTOR 5 mammalian target of rapamycin; PTLD 5 posttransplant lymphoproliferative disease; RCT 5 randomized controlled trial; SIRS 5 systemic infl ammatory response syndrome; TNF 5 tumor necrosis factor; TPMT 5 thiopurine methyltransferase

Benefit of adjunctive tacrolimus in connective tissue disease-interstitial lung disease

“…Careful monitoring of tacrolimus trough levels, blood pressure, electrolytes, and renal function permitted the chronic, safe co-administration of tacrolimus. Tacrolimus should be considered in patients who have failed conventional therapy or with severe and/or rapidly progressive ILD related to an idiopathic inflammatory myopathy or UCTD with careful clinical monitoring as outlined in the ACCP guidelines (31). …”

“…Laboratory monitoring included a complete metabolic panel, complete blood count and tacrolimus trough level drawn after initiation and 10–14 days after each dose adjustment and blood pressure was monitored. To limit toxicity, target 12-hour tacrolimus trough levels were 5–8 ng/mL, which is lower than that used in most post-transplant patients (31). Prophylaxis for pneumocystis jiroveci pneumonia was prescribed, usually with sulfamethoxazole/trimethoprim, which has been demonstrated to be safe and effective against this pathogen (32).…”

The Diagnosis and Treatment of Antisynthetase Syndrome

“…Prescribing providers should be familiar with evidence-based immunosuppressive clinical guidelines (33, 34). The aforementioned medications suppress normal immune function in an effort to combat aberrant pathogenic autoimmunity.…”

“…Patients receiving azathioprine should have their complete blood count and renal/liver function monitored every 1–3 months (33). Adverse reactions to azathioprine include nausea, pancreatitis, hepatitis, and cytopenias.…”

Nonsteroidal therapy of sarcoidosis

“…MTX has been the most widely studied cytotoxic drug for pulmonary and extrapulmonary sarcoidosis [2 ■ ]. The efficacy of MTX has also been demonstrated in cutaneous, ocular, musculoskeletal, and neurologic sarcoidosis [4]. Therefore, MTX is often the first DMASD used in sarcoidosis.…”