Table. Immunosuppressive potential of conventional (non-biological) immunosuppressive therapies

Immunosuppressant category	Drug(s)	Licensed indication(s)	Overall immunosuppressive potential	Mechanism of action	Half-life (mean)	Duration of immunosuppression
General	Hydroxychloroquine	Systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), malaria	Mild	Suppresses toll-like receptors to trigger important immunomodulatory effects, which impairs complement-dependent antigen-antibody reactions	About 40 days	Not typically considered as an immunosuppressant, but may lower lymphocyte count. Exact duration of immune recovery after drug discontinuation is not well defined
	Sulfasalazine Mesalazine Osalazine	RA, ulcerative colitis, Crohn’s disease	Mild	Immunomodulatory agents that block the production of COX-derived products of arachidonic acid metabolism	Sulfasalazine: about 10 hours Mesalazine: about 25 hours Olsalazine: about 55 minutes Olsalazine-S: 7 days due to slow dissociation from the protein binding site	Not typically considered as an immunosuppressant, but may lower lymphocyte count. Exact duration of immune recovery after drug discontinuation is not well defined
	Leflunomide	RA, psoriatic arthritis	Moderate	Inhibits pyrimidine synthesis, resulting in antiproliferative and anti-inflammatory effects	18–19 days; the active metabolite has a prolonged half-life of 1–4 weeks	Exact duration of potential immunosuppression is not well defined
	Teriflunomide	Multiple sclerosis	Moderate	Inhibits pyrimidine synthesis, which reduces deactivated lymphocytes in the central nervous system	18–19 days	Exact duration of potential immunosuppression is not well defined
	Mercaptopurine	Acute lymphoblastic leukaemia	Moderate	Inhibits DNA and RNA synthesis	1–5.4 hours	Exact duration of potential immunosuppression is not well defined
	Azathioprine ≤3 mg/kg/day	Rheumatic disorders	Mild	Inhibits purine and protein synthesis, which reduces circulating lymphocytes and immunoglobulin production	About 2 hours	Exact duration of potential immunosuppression is not well defined
	Azathioprine >3 mg/kg/day	Rheumatic disorders	Moderate		About 2 hours
	Azathioprine	Prevention of rejection in kidney transplant	Severe	Inhibits purine and protein synthesis, which reduces circulating lymphocytes and immunoglobulin production	About 2 hours	Immune recovery after transplant is impaired for at least 12 months
	Methotrexate ≤25 mg/week	RA, psoriasis arthritis	Mild	Folate antimetabolite that binds to dihydrofolate reductase, interfering with DNA synthesis, repair and cellular replication	1–15 hours	Lymphocyte recovery occurs 1–3 months after discontinuation. In RA, temporary discontinuation for 4 weeks improves some vaccine responses (eg for influenza)
	Methotrexate >25 mg/week	RA, psoriasis arthritis	Moderate		1–15 hours
	Methotrexate ≤25 mg/week	Oncology indications	Moderate	Folate antimetabolite that binds to dihydrofolate reductase, interfering with DNA synthesis, repair and cellular replication	1–15 hours	Exact duration of lymphocyte recovery is not defined in oncological populations
	Methotrexate >25 mg/week	Oncology indications	Severe		1–15 hours
	Mycophenolate	Prevention of rejection after organ transplant	Severe	Blocks DNA synthesis and exhibits a cytostatic effect on T- and B-lymphocytes	15–23 hours	Immune recovery after transplant is impaired for at least 12 months
	Cyclophosphamide (about 3 mg/kg/day)	Nephrotic syndrome	Moderate	Impairs DNA replication and transcription, resulting in altered cellular function and T- and B-lymphocyte depletion	3–12 hours	Exact duration of immune recovery is not well defined
	Cyclophosphamide (40–50 mg/kg/day)	Oncology indications	Severe		3–12 hours	Exact duration of immune recovery is not well defined
Calcineurin inhibitors	Ciclosporin (0.25–5 mg/kg/day)	Psoriasis, RA	Mild	Inhibits the synthesis of interleukins (IL-2), which are essential for the self-activation of T-lymphocytes and their differentiation	6–20 hours	Exact duration of immune recovery is not defined in patients receiving this medication for rheumatic indications.
	Ciclosporin (about 5 mg/day or 6 mg/kg/day for children)	Nephrotic syndrome	Moderate		6–20 hours
	Ciclosporin (8–12 mg/kg/day for children)	Prevention of rejection after organ transplant	Severe		6–20 hours	Immune recovery after transplant is impaired for at least 12 months
	Tacrolimus	Prevention of rejection after organ transplant	Severe	Inhibits T-cell activation	10–46 hours	Immune recovery after transplant is impaired for at least 12 months
Mammalian target of rapamycin (mTOR) inhibitors	Sirolimus (1–2 mg/day)	Lymphangioleiomyomatosis	Moderate	Inhibits the regulatory kinase mTOR, which suppresses cytokine mediated T-cell proliferation	13–62 hours	Exact duration of potential immunosuppression is not well defined
	Sirolimus (2–5 mg/day)	Prevention of organ rejection after kidney transplant	Severe	Inhibits the regulatory kinase mTOR, which suppresses cytokine mediated T-cell proliferation	13–62 hours	Immune recovery after transplant is impaired for at least 12 months
	Everolimus (about 10 mg/day)	Oncology indications (eg breast cancer, renal cell carcinoma, neuroendocrine tumours)	Moderate	Reduces protein synthesis and induces cell growth arrest and apoptosis	About 30 hours	Exact duration of immunosuppression is not well defined in oncological populations
	Everolimus	Prevention of rejection after organ transplant	Severe	Reduces protein synthesis and induces cell growth arrest and apoptosis	About 30 hours	Immune recovery after transplant is impaired for at least 12 months
Note: This is not an exhaustive list. Licensed indications were referenced from database of the Australian Therapeutic Goods Administration (TGA). Furthermore, the underlying disease for which the medication is prescribed, and concomitant immunosuppressant use, may alter this categorisation. For further information regarding the immunosuppressive potential of underlying conditions, please also consider Table. Immunosuppressive potential of certain medical conditions.

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