Azasan

Other Immunosuppressants
Other Specific Antirheumatics

For storage information, see specific product information within the How Supplied section.
Hazardous Drug Classification
NIOSH 2016 List: Group 2
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
INJECTABLES: Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
ORAL TABLETS/CAPSULES/LIQUIDS: Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets will increase exposure and require additional protective equipment. Eye/face and respiratory protection may be needed during preparation and administration.

An extemporaneous suspension may be prepared by pulverizing 20 Imuran tablets, levigating with distilled water and 5 mL of Cologel, and adding it to a 2:1 simple syrup/cherry syrup mixture to make a total volume of 20 mL. The suspension contains 50 mg/mL of azathioprine and is stable for 8 weeks when stored in the refrigerator.
Alternatively, an azathioprine oral suspension may be prepared by pulverizing 120 azathioprine 50 mg tablets to a fine powder in a mortar and pestle. Add 40 mL of the vehicle (1:1 mixture of Ora-Sweet and Ora-Plus, 1:1 mixture of Ora-Sweet SF and Ora-Plus, or 1:4 mixture of cherry syrup concentrate and simple syrup) and mix to a uniform paste. Incrementally add more of the vehicle, mixing after each addition, to reach a total, final volume of 120 mL. The final suspension concentration is 50 mg/mL. The suspension is stable for 60 days when protected from light and stored either under refrigeration at 5 degrees C or at room temperature of 25 degrees C. In the study, clear amber plastic (polyethylene terephthalate) bottles were used to store the suspension.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Reconstitution:
Reconstitute 100 mg by adding 10 mL of sterile water for injection to the vial to give a concentration of 10 mg/mL.
The reconstituted solution should be clear and should be used within 24 hours.
 
Intravenous injection/infusion:
NOTE: Azathioprine reconstituted solution is only for intravenous administration; the pH is approximately 9.6.
Inject appropriate dose directly into a vein or further dilute appropriate dose in 0.9% Sodium Chloride or 5% Dextrose for IV infusion.
For IV infusion, the dose may be further diluted with sterile saline or dextrose; the final volume depends on time for the infusion, which is usually 30 to 60 minutes but may be as short as 5 minutes and as long as 8 hours for the daily dose.

leukopenia / Delayed / 5.3-16.0
pancytopenia / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
veno-occlusive disease (VOD) / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
serum sickness / Delayed / Incidence not known
lymphoma / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
leukoencephalopathy / Delayed / Incidence not known

thrombocytopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
bleeding / Early / Incidence not known
ascites / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
pneumonitis / Delayed / Incidence not known

infection / Delayed / 0-20.0
vomiting / Early / 12.0-12.0
nausea / Early / 12.0-12.0
diarrhea / Early / Incidence not known
abdominal pain / Early / Incidence not known
myalgia / Early / Incidence not known
steatorrhea / Delayed / Incidence not known
fever / Early / Incidence not known
malaise / Early / Incidence not known
arthralgia / Delayed / Incidence not known
rash / Early / Incidence not known
alopecia / Delayed / Incidence not known

Azathioprine therapy requires an experienced clinician who is familiar with the mutagenic potential and risk of hematological toxicities associated with the drug. Increased susceptibility to a new primary malignancy, particularly of the skin, results from chronic immunosuppression with azathioprine. Patients with rheumatoid arthritis previously treated with alkylating agents such as cyclophosphamide, chlorambucil, or melphalan may have a prohibitive risk of neoplasia if treated with azathioprine; azathioprine is contraindicated for use by such patients. Reports of malignancy include post-transplant lymphoma and hepatosplenic T-cell lymphoma (HSTCL) in patients with inflammatory bowel disease. Inform patients about the malignancy risk, and instruct patients to limit sunlight (UV) exposure by wearing protective clothing and by using a sunscreen with a high protection factor.

Azasan, Imuran

Rx

Oral and parenteral thiopurine immunosuppressive agent; metabolized to 6-mercaptopurine
Commonly used in transplant patients but also is useful in RA, lupus nephritis, and psoriatic arthritis
In gastroenterology, used in the treatment of Crohn's disease and ulcerative colitis

3 to 5 mg/kg PO once daily beginning on the day of or 1 to 3 days prior to transplantation. Maintenance dosage is 1 to 3 mg/kg PO once daily. This dosage may vary with patient response. Do NOT increase the azathioprine dose to toxic levels because of threatened rejection. Azathioprine discontinuation may be necessary for severe hematologic or other toxicity even if rejection of the homograft may be a consequence of drug withdrawal. According to renal transplant guidelines, an antiproliferative agent such as azathioprine is to be used for initial maintenance immunosuppression with a calcineurin inhibitor such as tacrolimus plus or minus corticosteroids. Of note, mycophenolate is suggested to be the first-line antiproliferative agent.

1 to 2 mg/kg/day PO plus tacrolimus and corticosteroids led to a survival free of graft loss in 89.6% and a survival free from rejection in 68.7% of 93 patients 2 years after transplantation, According to renal transplant guidelines, an antiproliferative agent such as azathioprine is to be used for initial maintenance immunosuppression with a calcineurin inhibitor such as tacrolimus plus or minus corticosteroids. Of note, mycophenolate is suggested to be the first-line antiproliferative agent.

NOTE: Intravenous administration of the sodium salt is indicated only in patients unable to tolerate oral medications.

3 to 5 mg/kg IV once daily beginning on the day of or 1 to 3 days prior to transplantation. Maintenance dosage is 1 to 3 mg/kg IV once daily. Patients may be switched to oral therapy as soon as is practical. Do NOT increase the azathioprine dose to toxic levels because of threatened rejection. Azathioprine discontinuation may be necessary for severe hematologic or other toxicity even if rejection of the homograft may be a consequence of drug withdrawal. According to renal transplant guidelines, an antiproliferative agent such as azathioprine is to be used for initial maintenance immunosuppression with a calcineurin inhibitor such as tacrolimus plus or minus corticosteroids. Of note, mycophenolate is suggested to be the first-line antiproliferative agent.

Initially, 1 mg/kg/day (50 to 100 mg) PO can be administered as a single dose or in divided doses. If patient response is not satisfactory within 6 to 8 weeks, dosage may be increased by 0.5 mg/kg/day at 4 week-intervals. Maximum daily dose: 2.5 mg/kg/day. An adequate trial should be a minimum of 12 weeks; patients not improved after 12 weeks can be considered refractory. Azathioprine may be continued long-term in patients with clinical response, but patients should be monitored carefully, and gradual dosage reduction should be attempted to reduce risk of toxicities. Maintenance dosage should be reduced by 0.5 mg/kg or approximately 25 mg daily every 4 weeks while other therapy is kept constant until the minimum effective dose is achieved. The optimum duration of maintenance azathioprine has not been determined. Doses of 1.1 to 3 mg/kg/day have been used in the treatment of RA and have been found equivalent to therapeutic doses of cyclophosphamide.

2 to 2.5 mg/kg/day PO. Azathioprine is recommended as a first-line treatment for gastrointestinal, neurological, ocular, and vascular disease manifestations. Consider azathioprine for recurrent mucocutaneous disease manifestations and recurrent and chronic articular disease manifestations.

50 mg PO once daily, initially. Increase the dose to 2.5 mg/kg/day after 2 weeks as tolerated. Guidelines state that azathioprine may be used in treatment of active Crohn's disease. Azathioprine alone is not more effective than placebo to induce remission; however, it is effective for maintenance of remission in patients with Crohn's disease. Once remission is induced with corticosteroids, a thiopurine should be considered for use for steroid-sparing. Patients who are steroid dependent should be started on thiopurines with or without anti-TNF therapy. Azathioprine, typically at reduced doses, can also be used as adjunctive therapy for reducing immunogenicity against biologic therapy.

25 mg PO once daily, initially. Increase the dose to 1.25 mg/kg/day after 2 weeks as tolerated. Guidelines state that azathioprine may be used in treatment of active Crohn's disease. Azathioprine alone is not more effective than placebo to induce remission; however, it is effective for maintenance of remission in patients with Crohn's disease. Once remission is induced with corticosteroids, a thiopurine should be considered for use for steroid-sparing. Patients who are steroid dependent should be started on thiopurines with or without anti-TNF therapy. Azathioprine, typically at reduced doses, can also be used as adjunctive therapy for reducing immunogenicity against biologic therapy.

2 to 2.5 mg/kg/day PO is the usual initial and maximal target dose range recommended for maintenance of steroid-free remission in children at risk for poor disease outcome. Thiopurines alone are not recommended as induction therapy. Consider thiopurine methyltransferase (TPMT) genotyping or enzymatic activity testing prior to initiating therapy, as doses need to be adjusted based on metabolizer status.

50 mg PO once daily, initially. Increase dose to 2.5 mg/kg/day after 2 weeks if white blood cell count is 4 x 109 or more and has not decreased by more than 50% from baseline and liver function tests and amylase are not rising. Consider thiopurine methyltransferase (TPMT) genetic or enzyme activity testing before initiating therapy; dosage adjustments may be necessary. Guidelines recommend thiopurines for maintenance of remission for persons with moderate to severely active ulcerative colitis after steroid induction. Guidelines do not recommend thiopurine monotherapy for induction of remission.

2 to 2.5 mg/kg/dose PO once daily. Consider thiopurine methyltransferase (TPMT) genetic or enzyme activity testing before initiating therapy; dosage adjustments may be necessary. Thiopurines monotherapy is not recommended as induction therapy. Thiopurines may be somewhat more effective than 5-ASA products for maintaining remission in ulcerative colitis; however, considering their safety profile, generally reserve thiopurines for second-line therapy after 5-ASA has failed.

Doses up to 2 mg/kg/day PO to reduce glucocorticoid requirement or to control clinically active class III, IV, or V disease that is moderate to severe in pregnant patients; 2 mg/kg/day PO +/- low dose daily glucocorticoids is also a recommended option for maintenance therapy of class III/IV disease for those who respond to induction therapy with mycophenolate mofetil (MMF) or cyclophosphamide and for maintenance therapy of class V disease without proliferative changes and with proteinuria greater than 3 g/24 hours who respond to induction therapy with prednisone and mycophenolate. Fewer patients with active class III, IV, or V disease who had a clinical response to induction with either MMF or cyclophosphamide had treatment failure during maintenance therapy with MMF PO 2 g/day (16.4%) as compared with azathioprine 2 mg/kg/day PO recipients (32.4%) (HR, 0.44; 95% CI, 0.25 to 0.77, p = 0.003). Treatment failure was defined as death, end-stage renal disease, doubling of the serum creatinine concentration, renal flare, or rescue therapy need.

2 to 3 mg/kg/day PO in 2 to 3 divided doses. Consider tapering dose to less than 2 mg/kg/day in persons in remission. Usual maintenance dose: 50 to 100 mg/day.

2 to 3 mg/kg/day (Max: 150 mg/day) PO in 2 to 3 divided doses. Consider tapering dose to less than 2 mg/kg/day in persons in remission.

25 to 50 mg PO once daily, initially. Increase the dosage by 25 to 50 mg PO every 1 to 2 weeks up to 1.5 to 3 mg/kg/day (Max: 250 mg/day) PO in 1 or 2 divided doses.

1.5 to 3 mg/kg/day (Max: 250 mg/day) PO in 1 or 2 divided doses.

Doses of 2 to 3 mg/kg PO once daily for 12 to 18 months after complete remission have been recommended.

2 mg/kg PO once daily has been recommended.

The following regimen has been recommended: initially, 50 mg PO once daily for 1 week, then increase gradually to 2 to 3 mg/kg/day PO. Base dosage on total body weight even in obese patients but do not exceed 250 mg/day.

50 to 100 mg PO once daily, initially. May increase the dose up to 150 mg/day if needed. When biochemical remission is achieved, use the lowest dose necessary to maintain remission.  Guidelines recommend budesonide or prednisone in combination with azathioprine as first-line therapy in adults who present with autoimmune hepatitis (AIH) who do not have cirrhosis, acute severe AIH, or acute liver failure. Add azathioprine to prednisone after 2 weeks in persons with compensated cirrhosis, and consider addition of azathioprine after cholestasis is resolved in persons with acute severe AIH. May consider immunosuppression withdrawal, if appropriate, after prolonged biochemical remission (i.e., 24 months) for persons with AIH or AIH with cirrhosis; do not withdraw immunosuppression in persons presenting with acute severe AIH.

1 to 2 mg/kg/dose (Max: 50 to 100 mg/dose) PO once daily, initially. May increase the dose up to 150 mg/day if needed. When biochemical remission is achieved, use the lowest dose necessary to maintain remission. Guidelines recommend budesonide or prednisone in combination with azathioprine as first-line therapy in adults who present with autoimmune hepatitis (AIH) who do not have cirrhosis, acute severe AIH, or acute liver failure. Add azathioprine to prednisone after 2 weeks in persons with compensated cirrhosis, and consider addition of azathioprine after cholestasis is resolved in persons with acute severe AIH. May consider immunosuppression withdrawal, if appropriate, after prolonged biochemical remission (i.e., 24 months) for persons with AIH or AIH with cirrhosis; do not withdraw immunosuppression in persons presenting with acute severe AIH.

2 to 3 mg/kg/day PO to a maximum dose of 150 mg/day PO. Dosing should begin at 25 to 50 mg/day PO and increase gradually, by 25-mg increments, every 7 to 14 days until the maximum dose is reached. Guidelines suggest treatment should be in combination with prednisone and continue for a minimum of 6 months. Objective responses may not be noted until the patient has received 3 months of therapy or more. Exact duration of treatment and need for long-term maintenance should be individualized based on clinical response and tolerance to therapy.

1 to 3 mg/kg/dose PO once daily. Baseline thiopurine methyltransferase (TPMT) concentration testing is recommended before initiation, with avoidance of use in those with very low or absent enzyme activity.

1 to 4 mg/kg/dose PO once daily. Usual dose: 2.5 mg/kg/dose PO once daily. Assess thiopurine methyltransferase (TPMT) concentrations at baseline and repeat testing if nonresponse or change in responsenon.

Limited data suggest doses of 1.5 to 3 mg/kg/day orally may be effective. The recommended maximum dosage in dermatologic disease 150 mg/day or less orally. The largest study of azathioprine in psoriasis included 29 patients administered doses of 100 to 300 mg/day PO. A greater than 75% improvement was reported in 13 patients and 6 patients exhibited greater than 50% improvement. In a smaller study comprised of mostly treatment-resistant patients, a dose of 2.5 mg/kg/day PO resulted in greater than 25% improvement in 5/10 patients.

1 mg/kg/day PO once daily or divided twice daily; gradually increase dose to 2 to 3 mg/kg/day for several months.

2 to 2.5 mg/kg/dose PO once daily for several months.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Promptly discontinue azathioprine if veno-occlusive disease occurs.

Dosage should be modified depending on clinical response and degree of renal impairment, but no quantitative recommendations are available. Relatively oliguric patients, especially those with tubular necrosis in the immediate postcadaveric transplant period, may have delayed clearance of azathioprine or its metabolites, may be particularly sensitive to azathioprine, and are usually given lower doses.

Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Azathioprine may interact with other drugs that are myelosuppressive, such as azathioprine. A significant toxicity of zidovudine, ZDV is myelosuppression and resulting neutropenia and anemia.
Abatacept: (Moderate) Concomitant use of immunosuppressives may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection.
Acetaminophen; Ibuprofen: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Adalimumab: (Moderate) The safety and efficacy of adalimumab in patients with immunosuppression have not been evaluated. Patients receiving azathioprine along with adalimumab may be at a greater risk of developing an infection.
Albuterol; Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Allopurinol: (Major) Concomitant use of allopurinol with azathioprine can result in a large increase in azathioprine activity and toxicity (e.g., bone marrow suppression, leukopenia, pancytopenia). The interaction is well-documented (i.e., multiple case reports over the course of decades) and can be potentially life-threatening. The increase in azathioprine activity is due to the ability of allopurinol to inhibit xanthine oxidase-controlled metabolism, thereby decreasing the elimination of azathioprine. When possible, this drug combination should be avoided. If avoidance of cotherapy is not possible, a reduced dosage of azathioprine (e.g., reduce to one-third to one-quarter of the original dose and close hematologic monitoring are required. Further azathioprine dosage reduction or use of an alternative therapy is recommended for patients who have low or absent thiopurine methyltransferase activity, as both the thiopurine methyltransferase and xanthine oxidase pathways are affected.
Alpha interferons: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Amlodipine; Benazepril: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Amlodipine; Celecoxib: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Angiotensin-converting enzyme inhibitors: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Azelastine; Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Balsalazide: (Moderate) 5-aminosalicylates (e.g., sulfasalazine, mesalamine, olsalazine) may interact with azathioprine and increase the risk of azathioprine-related toxicity. The inhibition of thiopurine methyltransferase activity, one of the enzymes responsible for azathioprine metabolism, by 5-aminosalicylates has been described via in vitro and in vivo study. Theoretically, this interaction could result in a higher risk of bone marrow suppression or other azathioprine dose-related side effects. If concurrent therapy cannot be avoided, closely monitor platelet and complete blood cell counts.
Baricitinib: (Major) Concomitant use of baricitinib with azathioprine is not recommended because of the possibility of additive immunosuppression and increased infection risk. There is insufficient experience to assess the safety and efficacy of this combination. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Basiliximab: (Minor) Because azathioprine is an immunosuppressant with myelosuppressive actions, additive affects may be seen with other immunosuppressives.
Beclomethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Benazepril: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Benazepril; Hydrochlorothiazide, HCTZ: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Betamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Budesonide; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Budesonide; Glycopyrrolate; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Bupivacaine; Meloxicam: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Captopril: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Captopril; Hydrochlorothiazide, HCTZ: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Carbamazepine: (Minor) Azathioprine should be used cautiously in patients receiving carbamazepine, due to the potential for additive bone marrow/hematologic effects.
Celecoxib: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Celecoxib; Tramadol: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Certolizumab pegol: (Moderate) The safety and efficacy of certolizumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with certolizumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy who received certolizumab.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciclesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Corticosteroids: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Cortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Cyclophosphamide: (Moderate) Monitor hepatic function if coadministration of cyclophosphamide with azathioprine is necessary as there is an increased risk of hepatotoxicity (liver necrosis).
Deflazacort: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Dexamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Diclofenac: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Diclofenac; Misoprostol: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Diflunisal: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Diphenhydramine; Ibuprofen: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Diphenhydramine; Naproxen: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Enalapril, Enalaprilat: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Enalapril; Hydrochlorothiazide, HCTZ: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Etodolac: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Febuxostat: (Contraindicated) The use of febuxostat with azathioprine is contraindicated. Febuxostat inhibits xanthine oxidase (XO) and is expected to greatly increase the concentrations of drugs metabolized substantially by this enzyme, such as azathioprine. Inhibition of XO by febuxostat may cause increased plasma concentrations of azathioprine, leading to serious toxicity. Drug interaction studies of febuxostat with azathioprine have not been conducted.
Fenoprofen: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Fludrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Flunisolide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Flurbiprofen: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluticasone; Salmeterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluticasone; Umeclidinium; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluticasone; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Formoterol; Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fosinopril: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Fosinopril; Hydrochlorothiazide, HCTZ: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Golimumab: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Hydrochlorothiazide, HCTZ; Moexipril: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Hydrocodone; Ibuprofen: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Hydrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Ibuprofen: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Ibuprofen; Famotidine: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Ibuprofen; Oxycodone: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Ibuprofen; Pseudoephedrine: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Indomethacin: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Infliximab: (Moderate) Most infliximab recipients who developed serious infections were taking concomitant immunosuppressives such as methotrexate or corticosteroids. The concurrent use of infliximab and immunosuppressants may also contribute to malignancy risk. However, the use of concomitant immunosuppressives such as 6-mercaptopurine, azathioprine, or methotrexate with infliximab appeared to reduce the frequency of antibodies to infliximab. Patients with Crohn's disease receiving immunosuppressives tended to have fewer infusion-related reactions as compared to patients not receiving immunosuppressive therapy. Also, concomitant methotrexate use, for example, may increase infliximab concentrations. Patients who were antibody-positive were more likely to have higher rates of infliximab clearance and reduced efficacy than were patients who were antibody negative. For patients with inflammatory bowel disease especially adolescents and young adults, consider the possibility that there is a higher risk of hepatosplenic T-cell lymphoma with combination therapy versus an observed increased risk of immunogenicity and hypersensitivity reactions with infliximab monotherapy from the clinical trial data.
Interferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Interferon Alfa-n3: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Intranasal Influenza Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Ketoprofen: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Ketorolac: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Azathioprine may interact with other drugs that are myelosuppressive, such as azathioprine. A significant toxicity of zidovudine, ZDV is myelosuppression and resulting neutropenia and anemia.
Leflunomide: (Major) Concomitant use of azathioprine with leflunomide may increase the risk for hepatotoxicity. Caution and close monitoring are advised if these drugs are used together.
Lesinurad; Allopurinol: (Major) Concomitant use of allopurinol with azathioprine can result in a large increase in azathioprine activity and toxicity (e.g., bone marrow suppression, leukopenia, pancytopenia). The interaction is well-documented (i.e., multiple case reports over the course of decades) and can be potentially life-threatening. The increase in azathioprine activity is due to the ability of allopurinol to inhibit xanthine oxidase-controlled metabolism, thereby decreasing the elimination of azathioprine. When possible, this drug combination should be avoided. If avoidance of cotherapy is not possible, a reduced dosage of azathioprine (e.g., reduce to one-third to one-quarter of the original dose and close hematologic monitoring are required. Further azathioprine dosage reduction or use of an alternative therapy is recommended for patients who have low or absent thiopurine methyltransferase activity, as both the thiopurine methyltransferase and xanthine oxidase pathways are affected.
Lisinopril: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Lisinopril; Hydrochlorothiazide, HCTZ: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Meclofenamate Sodium: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Mefenamic Acid: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Meloxicam: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Mercaptopurine, 6-MP: (Contraindicated) Mercaptopurine, 6-MP is an active metabolite of azathioprine. Concurrent usage is, in essence, a duplication of pharmacologic therapy and may lead to overdosage. Co-therapy of azathioprine and 6-MP should be avoided to reduce the risk of a serious potential for drug-induced side effects and toxicity; case reports of severe immunosuppression and bone marrow suppression have occurred, and some of these cases have resulted in hospitalization, sepsis, and even patient mortality.
Mesalamine, 5-ASA: (Moderate) 5-aminosalicylates (e.g., sulfasalazine, mesalamine, olsalazine) may interact with azathioprine and increase the risk of azathioprine-related toxicity. The inhibition of thiopurine methyltransferase activity, one of the enzymes responsible for azathioprine metabolism, by 5-aminosalicylates has been described via in vitro and in vivo study. Theoretically, this interaction could result in a higher risk of bone marrow suppression or other azathioprine dose-related side effects. If concurrent therapy cannot be avoided, closely monitor platelet and complete blood cell counts.
Methylprednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Moexipril: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Mycophenolate: (Major) Concomitant use of mycophenolate and azathioprine is not recommended, as both drugs inhibit purine metabolism. Because azathioprine is an immunosuppressant with myelosuppressive actions, additive affects may be seen with other immunosuppressant agents (e.g., mycophenolate). Also, the drug combination has not been studied clinically.
Nabumetone: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Naproxen: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Naproxen; Esomeprazole: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Naproxen; Pseudoephedrine: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Natalizumab: (Major) Natalizumab for Crohn's disease should not be used in combination with immunosuppressants such as azathiorpine because of the potential for increased risk of progressive multifocal leukoencephalopathy and other serious infections. Ordinarily, patients with mulitple sclerosis who are receiving chronic immunosuppressant therapy should not be treated with natalizumab, for similar reasons.
Nonsteroidal antiinflammatory drugs: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Olopatadine; Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Olsalazine: (Moderate) 5-aminosalicylates (e.g., sulfasalazine, mesalamine, olsalazine) may interact with azathioprine and increase the risk of azathioprine-related toxicity. The inhibition of thiopurine methyltransferase activity, one of the enzymes responsible for azathioprine metabolism, by 5-aminosalicylates has been described via in vitro and in vivo study. Theoretically, this interaction could result in a higher risk of bone marrow suppression or other azathioprine dose-related side effects. If concurrent therapy cannot be avoided, closely monitor platelet and complete blood cell counts.
Oxaprozin: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Peginterferon Alfa-2a: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Peginterferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Perindopril: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Perindopril; Amlodipine: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with azathioprine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Piroxicam: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Prednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Prednisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Pretomanid: (Major) Avoid coadministration of pretomanid with azathioprine, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Quinapril: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Quinapril; Hydrochlorothiazide, HCTZ: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Ramipril: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Ribavirin: (Major) Pancytopenia and bone marrow suppression have been reported to occur within 3 to 7 weeks after concomitant administration of peginterferon alfa-2a / ribavirin and azathioprine. Inosine monophosphate dehydrogenase (IMDH) is required for one of the metabolic pathways of azathioprine and ribavirin is known to inhibit IMDH, thereby leading to the accumulation of the azathioprine metabolite, 6-methylthioinosine monophosphate (6-MTITP). This metabolite is associated with myelotoxicity (neutropenia, thrombocytopenia, and anemia). In the limited number of cases reported (n=8), myelotoxicity was reversible within 4 to 6 weeks after withdrawal of this combination of agents and did not recur upon reintroduction of either treatment alone. All drugs should be discontinued if patients experience pancytopenia and peginterferon alfa-2a / ribavirin should NOT be reintroduced with concomitant azathioprine. Patients receiving concomitant ribavirin and azathioprine should have complete blood counts, including platelet counts, monitored weekly for the first month of treatment, twice monthly for the second and third months of treatment, and monthly thereafter. After the third month of treatment, laboratory monitoring may be increased to more than monthly if dosage or other therapy changes are necessary.
Rilonacept: (Moderate) Patients receiving immunosuppressives along with rilonacept may be at a greater risk of developing an infection.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and azathioprine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Rituximab: (Moderate) The concomitant use of rituximab with other disease modifying anti-rheumatic drugs (DMARDs), such as azathioprine, may result in additive immunosuppression and an increased risk of infection. Monitor patients closely for signs or symptoms of infection.
Rituximab; Hyaluronidase: (Moderate) The concomitant use of rituximab with other disease modifying anti-rheumatic drugs (DMARDs), such as azathioprine, may result in additive immunosuppression and an increased risk of infection. Monitor patients closely for signs or symptoms of infection.
Ropeginterferon alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Rotavirus Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Sipuleucel-T: (Major) Concomitant use of sipuleucel-T and immunosuppressives should be avoided. Concurrent administration of immunosuppressives with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving immunosuppressives may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of immunosuppressives prior to initiating therapy with sipuleucel-T.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Azathioprine may interact with other drugs that are myelosuppressive. Drugs that may affect the production of leukocytes, including sulfamethoxazole; trimethoprim, SMX-TMP, may lead to exaggerated leukopenia, especially in patients who have received a renal transplant.
Sulfasalazine: (Moderate) 5-aminosalicylates (e.g., sulfasalazine, mesalamine, olsalazine) may interact with azathioprine and increase the risk of azathioprine-related toxicity. The inhibition of thiopurine methyltransferase activity, one of the enzymes responsible for azathioprine metabolism, by 5-aminosalicylates has been described via in vitro and in vivo study. Theoretically, this interaction could result in a higher risk of bone marrow suppression or other azathioprine dose-related side effects. If concurrent therapy cannot be avoided, closely monitor platelet and complete blood cell counts.
Sulindac: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Sumatriptan; Naproxen: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Tacrolimus: (Minor) Because azathioprine is an immunosuppressant with myelosuppressive actions, additive effects may be seen with other immunosuppressants. While therapy is designed to take advantage of this effect, patients may be predisposed to increased immunosuppression and myelosuppression, resulting in an increased risk of infection or other side effects. The risk is typically related to the intensity and duration of immunosuppression.
Tofacitinib: (Major) Concomitant use of tofacitinib with azathioprine is not recommended because of the possibility of additive immunosuppression and increased infection risk. There is insufficient experience to assess the safety and efficacy of this combination. Tofacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Tolmetin: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Trandolapril: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Trandolapril; Verapamil: (Major) The use of ACE inhibitors in hypertensive patients receiving azathioprine has been reported to induce anemia and severe leukopenia. This combination should be avoided where possible. When concurrent azathioprine and ACE inhibitor therapy is necessary, the patient should be monitored cautiously for potential myelosuppression.
Triamcinolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Trimethoprim: (Moderate) Azathioprine may interact with other drugs that are myelosuppressive. Drugs that may affect the production of leukocytes, including sulfamethoxazole; trimethoprim, SMX-TMP, may lead to exaggerated leukopenia, especially in patients who have received a renal transplant.
Typhoid Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Upadacitinib: (Major) Do not use upadacitinib in combination with potent immunosuppressants such as azathioprine. A risk of added immunosuppression exists when upadacitinib is coadministered with potent immunosuppressives. Combined use of multiple-dose upadacitinib with potent immunosuppressives has not been studied in patients with rheumatoid arthritis.
Valdecoxib: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Vigabatrin: (Major) Vigabatrin should not be used with other drugs like azathioprine that are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Warfarin: (Moderate) Azathioprine decreases warfarin serum concentrations and the INR and thus increases warfarin dosage requirements. If azathioprine is discontinued in a patient stabilized on warfarin, an increased risk of bleeding may occur. It is prudent to monitor the INR and response to warfarin prior to azathioprine initiation, frequently following initiation of azathioprine therapy, and again on azathioprine cessation. Adjust warfarin dosage based on INR and clinical response.
Yellow Fever Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Zidovudine, ZDV: (Moderate) Azathioprine may interact with other drugs that are myelosuppressive, such as azathioprine. A significant toxicity of zidovudine, ZDV is myelosuppression and resulting neutropenia and anemia.

Azasan/Azathioprine/Imuran Oral Tab: 50mg, 75mg, 100mg
Azathioprine/Azathioprine Sodium Intravenous Inj Pwd F/Sol: 100mg

2.5 mg/kg/day PO for RA; 3—5 mg/kg/day PO or IV for kidney transplant rejection prophylaxis.

2.5 mg/kg/day PO for RA; 3—5 mg/kg/day PO or IV for kidney transplant rejection prophylaxis.

Safety and efficacy have not been established. Doses of 1—2 mg/kg/day PO for kidney transplant rejection prophylaxis have been used.

Safety and efficacy have not been established. Doses of 1—2 mg/kg/day PO for kidney transplant rejection prophylaxis have been used.

Azathioprine decreases the metabolism of purines and may inhibit DNA and RNA synthesis as well. Azathioprine also may integrate into nucleic acids, resulting in chromosome breakage, nucleic acid malfunction, or the synthesis of faulty proteins. The drug may interfere with coenzyme functioning, thereby decreasing cellular metabolism, and may inhibit mitosis.
 
The immunosuppressive activity of azathioprine is due to its ability to inhibit the delayed hypersensitivity reaction and cellular cytotoxic activity that occur during renal allotransplantation. When used for the prevention of tissue rejection, azathioprine usually is administered in conjunction with local radiation therapy, corticosteroids, and other cytotoxic agents. The drug appears to be most effective during the early period of rejection and will not suppress secondary responses or established transplant rejections. Animal studies suggest that the drug is able to suppress the symptoms and the pathology of autoimmune disease.

Azathioprine can be given as an injection, but it is most commonly administered as oral tablets.
 
Azathioprine is metabolized to 6-mercaptopurine (6-MP) in the liver. Both azathioprine and 6-MP are rapidly eliminated from blood; neither azathioprine nor 6-MP is detectable in urine after 8 hours. Blood azathioprine concentrations are of little predictive value for therapy since the magnitude and duration of clinical effects correlate with thiopurine nucleotide concentrations in tissues rather than with plasma drug concentrations. Activation of 6-MP to form the major metabolites, 6-thioguanine nucleotides (6-TGNs), occurs via hypoxanthine-guanine phosphoribosyltransferase and a series of multi-enzymatic processes involving kinases. The cytotoxicity of azathioprine is partially due to the incorporation of 6-TGNs into DNA.[27993]
 
Inactivation of 6-MP occurs via two major pathways. The first pathway involves thiol methylation, catalyzed by thiopurine S-methyltransferase (TPMT), to form the inactive metabolite methyl-6-MP (6-MeMP). The second pathway is oxidation catalyzed by xanthine oxidase to produce an inactive metabolite 6-thiouric acid. TPMT activity has an inverse correlation with 6-TGN levels in erythrocytes and possibly other hematopoietic tissues, as these cells have little xanthine oxidase activity. Conversion of 6-TGNs to inactive 6-TG monophosphates occurs via the nucleotide diphosphatase (NUDT15) enzyme. Presence of genetic polymorphisms impact both TPMT and NUDT15 activity; thus, patients with reduced activity that receive usual azathioprine doses experience excessive accumulation of cellular concentrations of active 6-TGNs and increased risk of severe myelosuppression. Due to the risk of toxicity, alternative therapy should be considered in patients with homozygous TPMT or NUDT15 deficiency and dose modification in patients with heterozygous TPMT and/or NUDT15 deficiency.[27993]
 
The metabolites, as well as a small amount of unchanged azathioprine and 6-MP, are excreted in the urine. Proportions of metabolites are different in individual patients, which presumably accounts for variable magnitude and duration of drug effects. The metabolites, as well as a small amount of unchanged azathioprine and 6-MP, are excreted in the urine.

Azathioprine is well absorbed after oral administration, and both azathioprine and its major metabolite mercaptopurine distribute throughout the body and appear to cross the placenta. Azathioprine and mercaptopurine are about 30% bound to serum proteins.

Azathioprine is contraindicated for the treatment of rheumatoid arthritis in pregnant women. Positive evidence of human fetal risk exists based on investigational, marketing, or human studies, but the potential benefit to the mother may outweigh the potential risks to the fetus in some circumstances/diseases. Do NOT use azathioprine for the treatment of rheumatoid arthritis in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while taking azathioprine.

According to the manufacturer, azathioprine or breast-feeding should be discontinued because of the potential for tumorigenicity from azathioprine. The importance of azathioprine to the mother should determine whether to discontinue breast-feeding or discontinue azathioprine therapy. Azathioprine or its metabolites are transferred at low concentrations in breast milk. However, several small studies, including one with a median follow-up of 3.3 years, have not observed any adverse events in infants exposed to azathioprine through breast-feeding. If azathioprine is used by a lactating mother and there is concern for possible adverse effects in the infant, the following additional precautions could be taken: periodically monitor the infant's complete blood count with differential and liver function tests and/or avoiding breast-feeding for 4 to 6 hours after a dose to significantly reduce infant exposure. Consider the benefits of breast-feeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.