Immunosuppressants reduce the immune response to prevent transplant rejection and control autoimmune and inflammatory diseases. Older drugs suppress immunity broadly; biologic agents (large proteins made in living cells) and targeted small molecules block one cytokine, receptor, or cell type. The shared price of every drug in this topic is infection risk, and for some, malignancy.

Naming clue: "-mab" = monoclonal antibody; "-cept" = receptor fusion protein; "-tinib/-citinib" = small-molecule kinase inhibitor. Biosimilars are highly similar versions of a reference biologic (e.g., several infliximab and adalimumab biosimilars).

Transplant maintenance usually combines three drugs: a CNI + mycophenolate + a corticosteroid, so each can be given at a lower, less toxic dose.

Contraindications and cautions

• Active serious infection; untreated latent TB (treat TB infection before or with biologics per provider); hepatitis B surface antigen positive without antiviral prophylaxis
• Live vaccines during immunosuppression; give them at least 4 weeks before starting and inactivated vaccines at least 2 weeks before when possible
• TNF inhibitors: avoid in moderate to severe heart failure and demyelinating disease (multiple sclerosis)
• JAK inhibitors: caution with prior thrombosis, cardiovascular risk, smoking, age 50 or older, malignancy
• Tocilizumab: caution with diverticulitis
• Sirolimus: avoid immediately after surgery (wound dehiscence)

Pregnancy and lactation

• Mycophenolate: contraindicated — pregnancy test before starting and 8–10 days later, and contraception as defined by the US REMS (one highly effective method or two methods); stop before conception per the specialist
• Methotrexate: contraindicated — stop well before conception (at least 3 months in US ACR guidance; some non-US guidance allows 1 month)
• Leflunomide (RA DMARD): boxed warnings — embryo-fetal toxicity (contraindicated in pregnancy; pregnancy excluded before starting; reliable contraception) and severe hepatotoxicity (avoid in liver disease; ALT at baseline, monthly for 6 months, then every 6–8 weeks). Its active metabolite persists for up to 2 years, so before a planned pregnancy (or after a pregnancy or toxicity) the accelerated elimination procedure is used: cholestyramine 8 g three times daily for 11 days, then plasma teriflunomide below 0.02 mg/L confirmed on two tests at least 14 days apart
• Many TNF inhibitors, azathioprine, tacrolimus, and cyclosporine can be continued in pregnancy when benefits outweigh risks. Infants exposed in utero to biologics such as infliximab should not receive live vaccines (rotavirus, BCG) for about 6 months, per product labeling and specialist advice

Interactions

• CNIs and mTOR inhibitors are CYP3A4 substrates. Levels rise with grapefruit, azole antifungals, clarithromycin and erythromycin, diltiazem, verapamil, and ritonavir (toxicity). Levels fall with rifampin, carbamazepine, phenytoin, and St. John's wort (rejection)
• CNIs + potassium-sparing diuretics, ACE inhibitors, ARBs, or potassium supplements → hyperkalemia; + NSAIDs or aminoglycosides → nephrotoxicity
• Azathioprine + allopurinol or febuxostat → life-threatening marrow suppression (febuxostat contraindicated; azathioprine dose cut sharply if allopurinol must be used)
• Methotrexate + trimethoprim-sulfamethoxazole or NSAIDs → marrow toxicity; alcohol → liver injury
• Mycophenolate: antacids and cholestyramine reduce absorption
• Combining biologics (e.g., two TNF or JAK agents) is not done — additive infection risk

1. Infection surveillance first: fever may be blunted, so report low-grade fever, cough, dysuria, new rash, or wound change promptly; hand hygiene; avoid staff and visitors with infections
2. Pre-biologic screening: IGRA or TST and chest X-ray for TB; hepatitis B (HBsAg, anti-HBc) and hepatitis C; HIV as indicated; CBC and liver tests; vaccination review
3. Trough levels for tacrolimus, cyclosporine, and sirolimus drawn just before the next dose; the target range is set by the transplant protocol (for tacrolimus commonly about 5–15 ng/mL, lower later after transplant). Give doses on time, the same way each day relative to food
4. Labs: creatinine, potassium, magnesium, glucose, CBC, liver tests, lipids; blood pressure at each visit. Methotrexate: CBC, liver tests, creatinine every 1–3 months when stable
5. Azathioprine: TPMT/NUDT15 before the first dose; CBC weekly at first
6. IV biologic infusions (infliximab, rituximab, antithymocyte globulin): premedicate as ordered (acetaminophen, antihistamine, corticosteroid); vital signs before, during, and after; start slowly and increase rate per protocol; emergency equipment and epinephrine at the bedside; stop the infusion for a reaction
7. Subcutaneous biologics: store refrigerated at 2–8 °C (36–46 °F); do not freeze or shake; let the pen warm to room temperature for about 30 minutes; rotate sites; sharps container
8. Skin cancer screening; age-appropriate cancer screening
9. Hazardous drug precautions for mycophenolate, azathioprine, and methotrexate tablets per institutional policy (do not crush; gloves)

• Never skip, stop, or change doses of transplant medicines — rejection can occur silently
• On lab days, take the morning dose after the blood draw
• Avoid grapefruit and grapefruit juice and St. John's wort; ask before any new medicine, including antibiotics and antifungals
• Report fever, chills, sore throat, cough, burning urination, or skin sores early; avoid crowds and sick contacts during high-risk periods; practice food safety
• No live vaccines (e.g., MMR, varicella, yellow fever, live zoster, intranasal influenza) unless approved; yearly inactivated influenza and other inactivated vaccines are recommended; household members should be vaccinated
• Sun protection and regular skin checks
• Methotrexate is taken once a week, on the same day — never daily; take folic acid; avoid alcohol
• Mycophenolate and methotrexate: use effective contraception; tell the provider before trying to conceive
• Tacrolimus: report tremor, headache, excess thirst or urination (hyperglycemia)
• Tell every provider (including dentists) that you take a biologic; carry a medication card; report signs of TB (cough lasting 2 weeks or more, night sweats, weight loss)

• Leflunomide toxicity (hepatotoxicity) or unplanned pregnancy: stop the drug and start cholestyramine accelerated elimination (activated charcoal is an alternative)
• Methotrexate toxicity (mucositis, pancytopenia, kidney injury), often from daily instead of weekly dosing: leucovorin (folinic acid) as the rescue antidote — start early; hydration and urine alkalinization for high-dose therapy; glucarpidase for toxic levels with kidney failure
• CNI toxicity (tremor, rising creatinine, hyperkalemia, confusion, seizures): no antidote — hold per provider, check trough, manage potassium, review interacting drugs
• Azathioprine or mycophenolate marrow suppression: hold; growth factor or transfusion as needed
• Infusion reaction or anaphylaxis: stop the infusion, maintain the IV line with saline, assess ABCs, IM epinephrine for anaphylaxis, notify the provider; a mild reaction may allow a slower restart per protocol
• Cytokine release syndrome (antithymocyte globulin, CAR T-cell therapy): fever, hypotension, hypoxia — supportive care and tocilizumab with or without corticosteroids
• Neutropenic fever in an immunosuppressed client is an emergency: cultures and IV antibiotics promptly

• All immunosuppressants → infection and malignancy risk; fever may be minimal
• Tacrolimus: nephrotoxicity, tremor, hyperglycemia, hyperkalemia; trough before the dose
• Cyclosporine: gum overgrowth, hirsutism, hypertension
• Grapefruit raises CNI levels; rifampin and St. John's wort lower them
• Mycophenolate: teratogenic — pregnancy tests and REMS contraception (one highly effective method or two methods); diarrhea, leukopenia
• Azathioprine: TPMT/NUDT15 testing; allopurinol/febuxostat interaction
• Methotrexate: once weekly, folic acid, no alcohol; toxicity → leucovorin
• Before TNF inhibitors and other biologics: TB (IGRA/TST) and hepatitis B screening
• TNF inhibitors: avoid in moderate–severe heart failure and multiple sclerosis
• No live vaccines during therapy; live vaccines at least 4 weeks before starting
• Rituximab: infusion reactions, HBV reactivation, PML
• JAK inhibitors: boxed warnings — infection, thrombosis, cardiovascular events, malignancy