Two generic<unk>  oral tablets, 50 mg each Nausea and vomiting are common adverse effects, especially at the beginning of a treatment. Such cases are met with taking<unk>  after meals or transient intravenous administration. Side effects that are probably hypersensitivity reactions include dizziness, diarrhea, fatigue, and rashes. Hair loss is often seen in transplant patients receiving the drug, but rarely occurs under other indications. Because<unk>  suppresses the bone marrow, patients can develop anaemia and be more susceptible to infection; regular monitoring of the blood count is recommended during treatment. Acute pancreatitis can also occur, especially in patients with Crohn's disease. Treatment is discontinued in up to 30% of patients due these effects but therapeutic drug monitoring of the biologically active metabolites, i.e. thiopurine nucleotides can help to optimize the efficacy and safety. Clinically, most hospitals resort to on-exchange LC-MS (liquid chromotography - mass spectrometry) but the newly developed approach of porous graphitic carbon based chromatography hyphenated with mass spectrometry appears superior with respect to patient care in this respect. Under FDA rules, like many other immunosuppressants, the use of this drug excludes eligibility for blood donation. It is listed by the International Agency for Research on Cancer as a group 1 carcinogen (carcinogenic to humans). Pharmacogenetics The enzyme thiopurine S-methyltransferase (TPMT) is responsible for various activation and deactivation steps in<unk> 's mechanism of action. The first metabolic step that<unk>  undergoes in the body is the conversion to 6-mercaptopurine (6-MP; see Pharmacokinetics), which is itself an immunosuppressant prodrug. The TPMT enzyme is responsible, in part, for the methylation of 6-MP into the inactive metabolite 6-methylmercaptopurine - this methylation prevents 6-MP from further conversion into active, cytotoxic thioguanine nucleotide (TGN) metabolites. Certain genetic variations within the TPMT gene can lead to decreased or absent TPMT enzyme activity, and individuals who are homozygous or heterozygous for these types of genetic variations may have increased levels of TGN metabolites and an increased risk of severe bone marrow suppression (myelosuppression) when receiving<unk> . In many ethnicities, TPMT polymorphisms that result in decreased or absent TPMT activity occur with a frequency of approximately 5%, meaning that about 0.25% of patients are homozygous for these variants. However, an assay of TPMT activity in red blood cells or a TPMT genetic test can identify patients with reduced TPMT activity, allowing for the adjustment of<unk>  dose or avoidance of the drug entirely. The FDA-approved drug label for<unk>  recommends testing for TPMT activity to identify patients at risk for myelotoxicity. Indeed, testing for TPMT activity is one of the few examples of pharmacogenetics being translated into routine clinical care. Missense SNP in NUDT15 (e.g., rs116855232, inducing R139C)) has been identified to be a causal factor for<unk> -induced leukopenia through a genome wide association study (GWAS) in East Asians. Cancers<unk>  is listed as a human carcinogen in the 12th Report on Carcinogens by the National Toxicology Program of U.S. Department of Health and Human Services, asserting that it is "known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans." Since August 2009, the U.S. FDA has required warnings to be placed on packaging with respect to increased risks of certain cancers. The risks involved seem to be related both to the duration and the dosage used. People who have previously been treated with an alkylating agent may have an excessive risk of cancers if treated with<unk> . Epidemiological studies by International Agency for Research on Cancer have provided "sufficient" evidence of<unk>  carcinogenicity in humans (group 1), although the methodology of past studies and the possible underlying mechanisms are questioned. The various diseases requiring transplantation may in themselves increase the risks of non-Hodgkin lymphoma, squamous cell carcinomas of the skin, hepatobiliary carcinomas, and mesenchymal tumours to which<unk>  may add additional risks. Those receiving<unk>  for rheumatoid arthritis may have a lower risk than those undergoing transplantation. Cases of hepatosplenic T-cell lymphoma – a rare type of lymphoma – have been reported in patients treated with<unk> . The majority occurred in patients with inflammatory bowel disease. Adolescents and young adult males were the majority of cases. They presented with a very aggressive disease course, and with one exception, died of the lymphoma. The FDA has required changes to the labeling to inform users and clinicians of the issue. Skin cancers In transplant patients, skin cancer is 50 to 250 times more common than in the general population, and between 60 and 90% of patients are affected 20 years after transplantation. The use of immunosuppressive medication including<unk>  in organ transplantation has been linked to increased rates of developing skin cancer.<unk>  causes the accumulation of 6-thioguanine (6-TG) in patients' DNA, which might trigger cancer when the patient is later exposed to ultraviolet light. Patients taking<unk>  were found to be abnormally sensitive to UVA light.
Azathioprine
Hydroxychloroquine
Etanercept
Aminophenazone
Tofacitinib
Teriflunomide
Leflunomide
Sirolimus