Immunosuppressants (transplant + autoimmune)

◆Calcineurin inhibitors

• •Tacrolimus (Prograf) — most used post-transplant; inhibits IL-2 transcription
• •Cyclosporine — older; same MOA
• •BOTH: nephrotoxic (key SE — monitor Cr + drug levels), HTN, hyperglycemia, neurotoxicity (tremor)
• •Cyclosporine specific: gingival hyperplasia + hirsutism (cosmetic clue)
• •Tacrolimus specific: alopecia, more DM
• •Many drug interactions via CYP3A4 — azoles, macrolides, grapefruit ↑ levels; rifampin/phenytoin ↓

◆mTOR inhibitors

• •Sirolimus (rapamycin), everolimus
• •Used to spare nephrotoxic calcineurin inhibitors
• •Side effects: impaired wound healing (AVOID early post-op), hyperlipidemia, pneumonitis, anemia

◆Antimetabolites

• •Mycophenolate (MMF) — inhibits purine synthesis in lymphocytes; bone marrow suppression, GI
• •Azathioprine — converted to 6-MP; AVOID combination with allopurinol (↑ levels → toxicity) — reduce dose 75%
• •Test TPMT before starting azathioprine (deficiency → severe myelosuppression)
• •Methotrexate — RA, psoriasis, Crohn; folate antagonist; hepatotoxicity + pneumonitis; teratogen (categ X)

◆Corticosteroids

• •Mainstay for rejection bursts + chronic maintenance (slowly taper)
• •Long-term complications covered separately (osteoporosis, infection, DM, etc.)

◆Biologics

• •Basiliximab — IL-2 receptor antagonist; induction therapy at time of transplant
• •Anti-thymocyte globulin (ATG) — depletes T cells; used in induction or acute rejection
• •Rituximab (anti-CD20) — RA, lymphomas, transplant rejection; PML risk, screen for HepB reactivation
• •TNF inhibitors (infliximab, adalimumab, etanercept) — RA, psoriasis, IBD; reactivation of TB (screen with IGRA/PPD), HepB, fungal infections; cancer (lymphoma) risk slight ↑
• •Eculizumab (anti-C5) — paroxysmal nocturnal hemoglobinuria, atypical HUS; ↑ meningococcal infection (vaccinate first)
• •IL-17 / IL-23 inhibitors (secukinumab, ustekinumab) — psoriasis
• •JAK inhibitors (tofacitinib, baricitinib) — RA, alopecia areata; ↑ thrombosis, infections

◆Long-term risks in immunosuppressed

• •Infections: BK virus (kidney transplant nephropathy), CMV (give prophylaxis 3–6 mo post-transplant), PJP (TMP-SMX prophylaxis), reactivation TB
• •Cancers: skin (esp SCC — sun protection!), PTLD (post-transplant lymphoproliferative disorder — often EBV driven)
• •Vaccines: NO LIVE vaccines while immunosuppressed; ensure complete before transplant

Pre-biologic safety screen