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Other brands with the same active ingredient
These brands contain the same active ingredient (Azathioprine). Same strength and form. Confirm the switch with your doctor or pharmacist.
Indications & Uses
Imruza 50 is indicated for:
Pharmacology
Azathioprine is an immunosuppressive antimetabolite. Its chemical name is 6-[(1-methyl-4-nitro-1H-imidazol-5-yl)thio]-1H-purine, and it is an imidazolyl derivative of 6-mercaptopurine. Many of its biological effects are similar to those of the parent compound.
Azathioprine is an imidazole derivative of 6-mercaptopurine (6-MP). In the body it is quickly broken down into 6-MP and a methylnitroimidazole moiety. The 6-MP crosses cell membranes easily and is converted inside cells into several purine thioanalogues, including the main active nucleotide, thioinosinic acid. The rate of this conversion differs from one person to another. Nucleotides cannot cross cell membranes, so they do not circulate in body fluids.
Whether 6-MP is given directly or comes from azathioprine in the body, it is mostly eliminated as thiouric acid, an inactive oxidised metabolite. Xanthine oxidase, the enzyme that brings about this oxidation, is blocked by allopurinol. The activity of the methylnitroimidazole moiety has not been clearly defined. In several systems, though, it seems to change how azathioprine acts compared with 6-MP. Measuring plasma levels of azathioprine or 6-MP tells us nothing useful about how well these drugs will work or how likely they are to cause toxicity.
Because of these mechanisms, the therapeutic effect of azathioprine may only appear after several weeks or months of treatment. Azathioprine seems to be well absorbed from the upper gastro-intestinal tract. As with the plasma levels, the levels of azathioprine and 6-mercaptopurine do not correlate well with how effective or toxic the drug is.
Absorption: Azathioprine is well absorbed after it is taken by mouth. No food effect studies have been done on azathioprine itself, but pharmacokinetic studies on 6-mercaptopurine are relevant. The mean relative bioavailability of 6-mercaptopurine was about 27% lower when it was taken with food and milk than after an overnight fast. 6-mercaptopurine is also unstable in milk because of xanthine oxidase present there, with 30% degradation within 30 minutes. Azathioprine can be taken with food or on an empty stomach, but patients should keep to one method and not change it. The dose should not be taken with milk or dairy products.
After an oral dose of [35S]-azathioprine, the maximum plasma radioactivity occurs at 1-2 hours and falls with a half-life of 4-6 hours. This is not the half-life of azathioprine itself. It reflects how quickly azathioprine and the [35S]-containing metabolites leave the plasma. Azathioprine is mainly excreted in urine as 6-thiouric uric acid. A minor urinary product, 1-methyl-4-nitro-5-thioimidazole, has also been found. A small part of the drug may be cleaved between the S atom and the purine ring. Only a small amount of an azathioprine dose leaves the body in urine unchanged.
Biotransformation: Thiopurine S-Methyl Transferase (TPMT): TPMT activity is inversely related to the concentration of 6-mercaptopurine derived thioguanine nucleotides in red blood cells. Higher thioguanine nucleotide concentrations cause bigger drops in white blood cell and neutrophil counts. People with TPMT deficiency build up very high concentrations of cytotoxic thioguanine nucleotides.
Dosage Reference
Reference Information Only
Dosages shown are general references from official sources. Always consult your doctor or pharmacist for personalized dosing.
Adults:
Transplants: Depending on the immunosuppressive regimen used, a dose of up to 5 mg/kg body weight per day may be given by mouth or intravenously on the first day of treatment. The maintenance dose should range from 1 to 4 mg/kg body weight per day and must be adjusted according to clinical need and how well the blood counts tolerate the drug. Evidence indicates that azathioprine treatment should be continued indefinitely, even if only low doses are needed, because of the risk of graft rejection.
Other indications: In general, the starting dose is 1 to 3 mg/kg body weight per day, adjusted within these limits according to the clinical response (which may not be evident for weeks or months) and blood count tolerance. Once a therapeutic response is evident, reducing the maintenance dose to the lowest level that keeps that response should be considered. If the patient's condition has not improved within three months, withdrawing azathioprine should be considered. However, for patients with inflammatory bowel disease (IBD), a treatment duration of at least twelve months should be considered, and a response to treatment may not become clinically apparent until after three to four months. The maintenance dose needed may range from less than 1 mg/kg body weight per day to 3 mg/kg body weight per day, depending on the condition being treated and the individual patient's response, including blood count tolerance.
Overweight children: Children considered overweight may need doses at the higher end of the range, so close monitoring of the response to treatment is recommended.
Elderly: There is limited experience with giving azathioprine to elderly patients. Although the available data do not show that side effects are more common in elderly patients than in other patients treated with azathioprine, doses at the lower end of the range are recommended.
Renal impairment: In patients with reduced kidney function, a dose reduction should be considered.
Hepatic impairment: In patients with reduced liver function, a dose reduction should be considered.
Side Effects
For Imruza there is no modern clinical documentation that can be used as support for determining the frequency of undesirable effects. Infections and infestations: Very common: viral, fungal and bacterial infections in transplant patients receiving Imruza in combination with other immunosuppressants. Neoplasms benign, malignant and unspecified (including cysts and polyps): Rare: neoplasms including lymphoproliferative disorders, skin cancers (melanomas and non-melanomas), sarcomas (Kaposi's and non-Kaposi's), uterine cervical cancer in situ, acute myeloid leukaemia and myelodysplasia. Blood and lymphatic system disorders: Very common: depression of bone marrow function; leucopenia. Common: thrombocytopenia. Immune system disorders: Uncommon: hypersensitivity reactions. Respiratory, thoracic and mediastinal disorders: Very rare. Gastrointestinal disorders: Common: nausea.
Cautions & Contraindications
Warnings & Precautions
Monitoring Imruza (azathioprine) carries real hazards. It should be prescribed only if the patient can be properly monitored for toxic effects for as long as the treatment lasts. During the first 8 weeks, complete blood counts, including platelets, should be done weekly, or more often if the dose is high or if there is severe renal and/or hepatic disorder. The frequency can be reduced later in therapy, but counts should still be repeated monthly, or at intervals of not longer than 3 months. At the first sign of an abnormal fall in blood counts, treatment should be interrupted straight away, because leucocytes and platelets may keep falling even after the medicine is stopped. Patients taking Imruza should be told to report at once any sign of infection, unexpected bruising or bleeding, or other signs of bone marrow depression. Bone marrow suppression is reversible if Imruza is withdrawn early enough. Some people have an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT). They may be unusually sensitive to the myelosuppressive effect of Imruza and can develop rapid bone marrow depression soon after starting. The problem could get worse if Imruza is given together with drugs that inhibit TPMT, such as olsalazine, mesalazine or sulfasalazine. It has also been reported that decreased TPMT activity raises the risk of secondary leukaemias and myelodysplasia in people receiving 6-mercaptopurine (the active metabolite of Imruza) together with other cytotoxics. Some laboratories offer testing for TPMT deficiency, but these tests have not been shown to pick up every patient at risk of severe toxicity. So close monitoring of blood counts is still necessary. The dose of Imruza may need to be reduced when it is combined with other drugs whose primary or secondary toxicity is myelosuppression. Hepatotoxicity Imruza is hepatotoxic, and liver function tests should be checked routinely during treatment. Renal and/or hepatic insufficiency Take care when giving Imruza to patients with renal impairment and/or hepatic impairment. Mutagenicity Chromosomal abnormalities have been seen in both male and female patients treated with Imruza. Effects on fertility When chronic renal insufficiency was relieved by renal transplantation, with Imruza given as part of the treatment, fertility increased in both male and female transplant recipients. Carcinogenicity Patients on immunosuppressive therapy, including Imruza, have an increased risk of lymphoproliferative disorders and other malignancies. These are mainly skin cancers (melanoma and non-melanoma), sarcomas (Kaposi's and non-Kaposi's) and uterine cervical cancer in situ. The risk seems to be related to the degree and duration of immunosuppression. It has been reported that stopping immunosuppression may lead to partial regression of the lymphoproliferative disorder. A regimen containing several immunosuppressants (including thiopurines) should therefore be used with caution, as it could lead to lymphoproliferative disorders, some with reported fatalities. Giving multiple immunosuppressants together increases the risk of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders. Hepatosplenic T-cell lymphoma has been reported when Imruza is used alone or with anti-TNF agents or other immunosuppressants. Most reported cases were in people with IBD, but some have occurred outside that group. Patients on several immunosuppressive agents may be at risk of over-immunosuppression, so such therapy should be kept at the lowest effective level. Photosensitivity and risk of skin cancer Exposure to sunlight and UV light should be limited. Patients should wear protective clothing and use a sunscreen with a high protection factor, to lower the risk of skin cancer and photosensitivity. Varicella Zoster Virus Infection Infection with varicella zoster virus (VZV; chickenpox and herpes zoster) may become severe during treatment with immunosuppressants. Caution should be exercised. Progressive Multifocal Leukoencephalopathy (PML) PML, an opportunistic infection caused by the JC virus, has been reported in patients receiving Imruza with other immunosuppressive agents. Immunosuppressive therapy should be withheld at the first sign or symptom that suggests PML, and proper evaluation should be done to confirm the diagnosis. Hepatitis B Hepatitis B carriers (patients positive for hepatitis B surface antigen [HBsAg] for more than six months) and patients with documented past HBV infection are at risk of HBV reactivation if they receive immunosuppressive drugs. This shows as asymptomatic rises in serum HBV DNA and ALT levels. Local guidelines may be considered, including prophylactic therapy with oral anti-HBV agents. Macrophage activation syndrome Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in patients with autoimmune conditions, particularly inflammatory bowel disease (IBD). There could be an increased susceptibility to developing the condition with the use of Imruza.
Contraindications
Do not use if you are allergic to azathioprine or to any other ingredient in this preparation. A known allergy to 6-mercaptopurine should alert the prescriber to a likely allergy to azathioprine.
Pregnancy & Breastfeeding
Teratogenicity: Evidence for the teratogenicity of azathioprine in humans is inconclusive. As with any cytotoxic chemotherapy, both partners should be advised to use adequate contraceptive precautions while either one is receiving azathioprine.
Mutagenicity: Chromosomal abnormalities that disappear over time have been found in the lymphocytes of children born to patients treated with azathioprine. Except in extremely rare cases, no visible physical abnormalities have been observed in these offspring. Azathioprine combined with long wave ultraviolet light has shown a synergistic clastogenic effect in patients treated with azathioprine for various disorders.
Fertility: The specific effect of azathioprine therapy on human fertility is not known.
Pregnancy: Azathioprine and its metabolites are known to cross the placenta and amniotic membrane in substantial amounts, passing from mother to fetus. Azathioprine falls under Pregnancy Category D. It should not be given to patients who are pregnant or likely to become pregnant soon without a careful assessment of the risks against the benefits. As noted above, evidence for its teratogenicity in humans is inconclusive, and adequate contraceptive precautions should be used by either partner during treatment.
Women of childbearing potential and contraception for men and women: Because of azathioprine's genotoxic potential, women of childbearing potential should use effective contraception during treatment and for one month after finishing it. Men are advised to use effective contraception and avoid fathering a child while receiving azathioprine and for three months after completing treatment.
Lactation: Mothers receiving azathioprine are advised not to breastfeed, since 6 mercaptopurine has been detected in the colostrum and breast milk of women treated with the drug.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Overdose
Symptoms and signs: The main signs of Azathioprine overdosage are unexplained infection, ulceration of the throat, bruising and bleeding. They come from bone marrow depression, which may be at its worst after 9 to 14 days. These signs are more likely to appear after chronic overdosage than after a single acute overdose. One patient has been reported to have taken a single overdose of 7.5 g. The immediate toxic effects were nausea, vomiting and diarrhoea, followed by mild leucopenia and mild abnormalities in liver function. Recovery was uneventful.
Treatment: There is no specific antidote, so blood counts should be monitored closely and general supportive measures started if necessary. Active measures, such as activated charcoal, may not work unless they can be done within 60 minutes of ingestion. Further management should be as clinically indicated, or as the national poisons centre recommends where one is available. Whether dialysis helps after an Azathioprine overdose is not known, though the medicine is partially dialysable.
⚠️ In an emergency call 999 or go to the nearest hospital emergency department.
Storage
Keep Azathioprine below 25°C and away from light.
Drug Interactions
Common questions about Imruza 50 50 mg
What is Imruza 50 50 mg Tablet?
Imruza 50 50 mg Tablet is a medicine that contains Azathioprine. It is made by Beacon Pharmaceuticals PLC. It belongs to the Cytotoxic immunosuppressants group of medicines.
What is Imruza 50 used for?
Imruza 50 is used for: Inflammatory Bowel Disease, Rheumatoid Arthritis, Anemia.
What are the side effects of Imruza 50?
For Imruza there is no modern clinical documentation that can be used as support for determining the frequency of undesirable effects. Infections and infestations: Very common: viral, fungal and bacterial infections in transplant patients receiving Imruza in combination with other immunosuppressants.
Can I take Imruza 50 during pregnancy or while breastfeeding?
Teratogenicity: Evidence for the teratogenicity of azathioprine in humans is inconclusive. As with any cytotoxic chemotherapy, both partners should be advised to use adequate contraceptive precautions while either one is receiving azathioprine. Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
What happens if I take too much Imruza 50?
Symptoms and signs: The main signs of Azathioprine overdosage are unexplained infection, ulceration of the throat, bruising and bleeding. They come from bone marrow depression, which may be at its worst after 9 to 14 days. In an emergency call 999 or go to the nearest hospital emergency department.
How should I store Imruza 50?
Keep Azathioprine below 25°C and away from light.
Can I take other medicines with Imruza 50?
Some medicines can interact with Azathioprine, for example: Ribavirin, Febuxostat, Mesalazine [5-aminosalicylic acid], Dacarbazine, Mesalazine, Methotrexate. Tell your doctor or pharmacist about every medicine you take.
Do I need a prescription for Imruza 50?
Imruza 50 is a prescription (Rx) medicine. Take it as your doctor advises.