Azathioprine tablets should not be given during pregnancy without careful weighing of risk versus benefit. Conclusions Almost 9 of 10 physicians continue azathioprine throughout pregnancy. Auto-immune diseases 1-3 mg/kg/day. Azathioprine and mercaptopurine are moderately bound to serum proteins (30%) and are partially dialyzable. Severe bone marrow suppression may also occur. There are no adequate and well-controlled studies in pregnant women. That means two things: That means two things: Studies show a risk of adverse effects to … Williamson and Karp described an infant born with preaxial polydactyly whose mother received Azathioprine 200 mg daily and prednisone 20 mg every other day during pregnancy.6 Tallent et al described an infant with a large myelomeningocele in the upper lumbar region, bilateral dislocated hips, and bilateral talipes equinovarus. Clark JM. 0. 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. Azathioprine teratogenicity: review of the literature and case report. The dose of Azathioprine tablets required to prevent rejection and minimize toxicity will vary with individual patients; this necessitates careful management. Pregnancy category: D. Lactation: Drug excreted at low levels in breast milk; use not recommended. Pregnancy Category D. See WARNINGSsection. Toxicology Data Network. This drug should not be used for treating rheumatoid arthritis in pregnant women.3, Azathioprine tablets are teratogenic in rabbits and mice when given in doses equivalent to the human dose (5 mg/kg daily). This is not an estimate of the half-life of Azathioprine itself, but is the decay rate for all 35S-containing metabolites of the drug. Azathioprine is used with other medications to prevent transplant rejection (attack of the transplanted organ by the immune system) in people who received kidney transplants. In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, povidone and starch. B: May be acceptable. azathioprine A thiolated purine analogue/immunosuppressant used to prevent rejection of heart, kidney, lung and other allografts, acting primarily on T cells; it is used in rheumatoid arthritis and myasthenia gravis. Washington, DC: Division of Safety; Clinical Center Pharmacy Department and Cancer Nursing Services, National Institute of Health; 1992. Prevention of post-operative recurrence is a challenge in clinical practice in Crohn's disease. Immunomodulators, such as Azathioprine (Imuran®), 6-mercaptopurine (6-MP, Purinethol®), and cyclosporine A (Sandimmune®, Neoral®), appear low risk during pregnancy in standard dosages. ACTIVE LEARNING TEMPLATE: Medication STUDENT NAME_ Azathioprine MEDICATION_ REVIEW MODULE CHAPTER_ Category D- Use with Angiotensin-Converting Enzyme Inhibitors. They are classified as category X and C, respectively, and should not be used during pregnancy12 Reports of malignancy include post-transplant lymphoma and hepatosplenic T-cell lymphoma (HSTCL) in patients with inflammatory bowel disease. 0 thank. We comply with the HONcode standard for trustworthy health information -, Ostensen M "Optimisation of antirheumatic drug treatment in pregnancy." It is also used to treat severe rheumatoid arthritis (a condition in which the body attacks its own joints, causing pain, swelling, and loss of function) when other medications and treatments have not helped. J Rheumatol 20 (1993): 1152-7. Azathioprine (AZA), although a category D medication, can be used if the benefits outweigh the risks. The increased risk of malignancy following therapy with Azathioprine tablets should be explained to the patient. AU - Roblin, X. Patients receiving Azathioprine with ribavirin should have complete blood counts, including platelet counts, monitored weekly for the first month, twice monthly for the second and third months of treatment, then monthly or more frequently if dosage or other therapy changes are necessary. Physicians should inform patients of the risk of malignancy with Azathioprine. "Product Information. See WARNINGS. Accurate phenotyping (red blood cell TPMT activity) results are not possible in patients who have received recent blood transfusions (see CLINICAL PHARMACOLOGY, WARNINGS: Cytopenias, ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION sections). If the benefits of treatment with azathioprine (for instance, to maintain remission during pregnancy) outweigh the risks, this drug may be continued during pregnancy. National Study Commission on Cytotoxic Exposure. Early drug discontinuation may be considered in patients with abnormal CBC results that do not respond to dose reduction (see CLINICAL PHARMACOLOGY, WARNINGS: Cytopenias, and PRECAUTIONS: Laboratory Tests). These cases have had a very aggressive disease course and have been fatal. Recommendations for handling cytotoxic agents. Azathioprine has been classed as FDA category D – positive evidence of risk. Physicians using this drug should be very familiar with this risk as well as with the mutagenic potential to both men and women and with possible hematologic toxicities. Available from Louis P. Jeffrey, Chairman, National Study Commission on Cytotoxic Exposure. Heterozygous deficiency in TPMT and/or NUDT15. Maintenance therapy should be at the lowest effective dose, and the dose given can be lowered decrementally with changes of 0.5 mg/kg or approximately 25 mg daily every 4 weeks while other therapy is kept constant. Background: Although thiopurines are considered safe in humans, they are still pregnancy FDA category D drugs. Concomitant use of Azathioprine with febuxostat is not recommended. NUDT15 deficiency is detected in <1% of patients of European or African ancestry. The majority of reported cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Several guidelines on this subject have been published.15-21 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate. Last updated on Jan 1, 2020. American Society of Hospital Pharmacists. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. Consider the diagnosis of PML in any patient presenting with new-onset neurological manifestations and consider consultation with a neurologist as clinically indicated. Activation of 6-mercaptopurine occurs via hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and a series of multi-enzymatic processes involving kinases to form 6-thioguanine nucleotides (6-TGNs) as major metabolites. The cytotoxicity of Azathioprine is due, in part, to the incorporation of 6-TGN into DNA. The sodium salt of Azathioprine is sufficiently soluble to make a 10 mg/mL water solution which is stable for 24 hours at 59° to 77°F (15° to 25°C). Procedures for proper handling and disposal of this immunosuppressive antimetabolite drug should be considered. Azathioprine tablets, USP are indicated as an adjunct for the prevention of rejection in renal homotransplantation. Hepatotoxicity has been uncommon (less than 1%) in rheumatoid arthritis patients. See references. WARNING - MALIGNANCY Chronic immunosuppression with azathioprine, a purine antimetabolite increases risk of malignancy in humans. Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. View 2 more answers. Physicians should inform patients of the risk of malignancy with Azathioprine. Immunosuppressants: The immunosuppressive drugs azathioprine (Imuran [Pregnancy Category D]) and 6-mercaptopurine (Purinethol or 6-MP [Pregnancy Category D]) do cross the placenta and can be detected in cord blood. It is recommended that a further dose reduction or alternative therapies be considered for patients with low or absent TPMT activity receiving Azathioprine and xanthine oxidase inhibitors because both TPMT and XO inactivation pathways are affected (see CLINICAL PHARMACOLOGY, WARNINGS, PRECAUTIONS: Laboratory Tests and ADVERSE REACTIONS sections). Another inactivation pathway is oxidation, which is catalyzed by xanthine oxidase (XO) to form 6-thiouric acid. These include skin rashes, alopecia, fever, arthralgias, diarrhea, steatorrhea, negative nitrogen balance, reversible interstitial pneumonitis and hepatosplenic T-cell lymphoma (see Warnings Malignancy), and Sweet’s Syndrome (acute febrile neutrophilic dermatosis). Azathioprine has been reported to cause temporary depression in spermatogenesis and reduction in sperm viability and sperm count in mice at doses 10 times the human therapeutic dose;1 a reduced percentage of fertile matings occurred when animals received 5 mg/kg. Department of Adolescent and Child Health and Development. This drug should not be used for treating rheumatoid arthritis in pregnant women. Genetic polymorphisms influence TPMT and NUDT15 activity. The European Crohn's and Colitis Organisation consensus states that thiopurines should be considered in high-risk patients. Approximately 0.3% (1:300) of patients of European or African ancestry have two loss-of-function alleles of the TPMT gene and have little or no TPMT activity (homozygous deficient or poor metabolizers), and approximately 10% of patients have one loss-of-function TPMT allele leading to intermediate TPMT activity (heterozygous deficient or intermediate metabolizers). Pregnancy Category D is a classification given to medicines that have … These infections may lead to serious, including fatal outcomes. That means two things: That means two things: Studies show a risk of adverse effects … It works by decreasing the activity of the body's immune syst… Therapeutic response occurs after several weeks of treatment, usually 6 to 8; an adequate trial should be a minimum of 12 weeks. Azathioprine and hepatic veno-occlusive disease in renal transplant patients. Usual doses produce blood levels of Azathioprine, and of mercaptopurine derived from it, which are low (<1 mcg/mL). 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