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APO-AZATHIOPRINE is a brand name for Azathioprine, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: APO-AZATHIOPRINE (azathioprine tablets) is indicated for: • Renal Homotransplantation APO-AZATHIOPRINE is indicated as an adjunct for the prevention of rejection in renal homotransplantation. • Rheumatoid Arthritis APO-AZATHIOPRINE is indicated only in adult patients meeting criteria for classic or definite rheumatoid…
Verbatim from this product's HC label. Tap a section to expand.
2 Recommended Dose and Dosage Adjustment Renal Homotransplantation The dose of APO-AZATHIOPRINE required to prevent rejection and minimize toxicity will vary with individual patients; this necessitates careful management. The initial dose is usually 3 to 5 mg/kg daily, beginning at the time of transplant.
APO-AZATHIOPRINE is usually given as a single daily dose on the day of, and in a minority of cases one to three days before, transplantation. APO-AZATHIOPRINE is often initiated with the intravenous administration of the sodium salt, with subsequent use of tablets (at the same dose level) after the post- operative period.
Intravenous administration of the sodium salt is indicated only in patients APO-AZATHIOPRINE (Azathioprine Tablets) Page 6 of 35 unable to tolerate oral medications. Dose reduction to maintenance levels of 1 to 3 mg/kg daily is usually possible.
The dose of APO-AZATHIOPRINE should not be increased to toxic levels because of threatened rejection. Discontinuation may be necessary for severe hematologic or other toxicity, even if rejection of the homograft may be a consequence of drug withdrawal.
Rheumatoid Arthritis APO-AZATHIOPRINE is usually given on a daily basis. 0 mg/kg (50 to 100 mg) given as a single dose or on a twice daily schedule. The dose may be increased, beginning at six to eight weeks and thereafter by steps at four-week intervals, if there are no serious toxicities and if initial response is unsatisfactory.
5 mg/kg/day. Therapeutic response occurs after several weeks of treatment, usually six to eight; an adequate trial should be a minimum of 12 weeks. Patients not improved after twelve weeks can be considered refractory. APO- 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.
5 mg/kg or approximately 25 mg daily every four weeks, while other therapy is kept constant. The optimum duration of maintenance APO-AZATHIOPRINE has not been determined. APO-AZATHIOPRINE can be discontinued abruptly, but delayed effects are possible.
Rest, physiotherapy and salicylates should be continued while APO-AZATHIOPRINE is given, but it may be possible to reduce the dose of corticosteroids in patients on APO-AZATHIOPRINE. Use in Renal Dysfunction Relatively oliguric patients, especially those with tubular necrosis in the immediate post- cadaveric transplant period, may have delayed clearance of azathioprine or its metabolites, or be particularly sensitive to this drug, and are usually given lower doses.
Patients with rheumatoid arthritis previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan or others) may have a prohibitive risk of neoplasia if treated with APO- AZATHIOPRINE. Driving and Operating Machinery Due caution should be exercised when driving or operating a vehicle or potentially dangerous machinery.
Endocrine and Metabolism Administration of purine analogues (azathioprine and mercaptopurine) may interfere with the niacin pathway, potentially leading to nicotinic acid deficiency/pellagra. Few cases have been reported with the use of azathioprine, especially in patients with IBD (Crohn’s disease, colitis ulcerative).
Diagnosis of pellagra should be considered in a patient presenting with localised pigmented rash (dermatitis); gastroenteritis (diarrhoea); and widespread neurologic deficits, including cognitive decline (dementia). Dose reduction or discontinuation of azathioprine treatment should be considered based on careful benefit-risk assessment and appropriate medical care with niacin/nicotinamide supplementation should be initiated.
Gastrointestinal A gastrointestinal hypersensitivity reaction characterized by severe nausea and vomiting has been reported. These symptoms may also be accompanied by diarrhea, rash, fever, malaise, myalgias, elevations in liver enzymes, vasculitis, hepatic dysfunction, cholestatis and occasionally, hypotension.
Symptoms of gastrointestinal toxicity may often develop within the first several weeks of APO-AZATHIOPRINE therapy and are reversible upon discontinuation of the drug. The reaction can recur within hours after rechallenge with a single dose of APO- AZATHIOPRINE.
Hematologic Severe leukopenia and/or thrombocytopenia may occur in patients on APO-AZATHIOPRINE. APO-AZATHIOPRINE (Azathioprine Tablets) Page 10 of 35 Macrocytic anemia and severe bone marrow depression may also occur. Hematologic toxicities are dose related and may be more severe in renal transplant patients whose homograft is undergoing rejection.
1 Pregnant Women 05/2024 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES……………………………………………………………………………………………2 TABLE OF CONTENTS ...............................................................................................................
2 PART I: HEALTH PROFESSIONAL INFORMATION ....................................................................... 4 1 INDICATIONS .................................................................................................................
1 Pediatrics ................................................................................................................. 2 Geriatrics .................................................................................................................
4 2 CONTRAINDICATIONS ................................................................................................... 4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX .............................................................. 5 4 DOSAGE AND ADMINISTRATION ...................................................................................
2 Recommended Dose and Dosage Adjustment ........................................................ 5 5 OVERDOSAGE ............................................................................................................... 6 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ...................................
7 7 WARNINGS AND PRECAUTIONS .................................................................................... 1 Special Populations................................................................................................ 1 Pregnant Women ...............................................................................................
2 Breast-feeding ................................................................................................... 3 Pediatrics ...........................................................................................................
APO-AZATHIOPRINE is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
APO-AZATHIOPRINE (Azathioprine Tablets) Page 5 of 35
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Patients with NUDT15 variant Patients with inherited mutated NUDT15 gene are at increased risk for severe 6- mercaptopurine toxicity (See 7 WARNINGS AND PRECAUTIONS, Patients with NUDT15 variant). These patients generally require dose reduction; particularly those being NUDT15 variant homozygotes (See 7 WARNINGS AND PRECAUTIONS, Patients with NUDT15 variant).
Genotypic testing of NUDT15 variants may be considered before initiating 6-mercaptopurine therapy. In any case, close monitoring of blood counts is necessary.
It is suggested that patients on APO-AZATHIOPRINE have complete blood counts, including platelet counts, weekly during the first month, twice monthly for the second and third months of treatment, then monthly or more frequently if dosage alterations or other therapy changes are necessary.
Delayed hematologic suppression may occur. Prompt reduction in dosage or temporary withdrawal of the drug may be necessary if there is a rapid fall in, or persistently low leukocyte count or other evidence of bone marrow depression.
Leukopenia does not correlate with therapeutic effect; therefore, the dose should not be increased intentionally to lower the white blood cell count. There are individuals with an inherited deficiency of the enzyme thiopurine methyl-transferase (TPMT) who may be unusually sensitive to the myelosuppressive effect of azathioprine and prone to developing rapid bone marrow depression following the initiation of treatment with APO-AZATHIOPRINE.
This problem could be exacerbated by coadministration with drugs that inhibit TPMT, such as olsalazine, mesalazine or sulphasalazine. Also a possible association between decreased TPMT activity and secondary leukemias and myelodysplasia has been reported in individuals receiving 6-mercaptopurine (the active metabolite of azathioprine) in combination with other cytotoxics.
Some laboratories offer testing for TPMT deficiency, although these tests have not been shown to identify all patients at risk of severe toxicity. Therefore close monitoring of blood counts is still necessary. Hepatic/Biliary/Pancreatic Cholestasis of pregnancy, including foetal death, has been reported in association with azathioprine therapy.
If cholestasis of pregnancy occurs, dose reduction or discontinuation should be considered based on case by case risk-benefit profile assessment. g. fungal, viral and bacterial), including severe or atypical infection with varicella, herpes zoster and other infections agents (see 8 ADVERSE REACTIONS).
Fungal, viral, bacterial and protozoal infections may be fatal and should be treated vigorously. Reduction of azathioprine dosage and/or use of other drugs should be considered. Infection with varicella zoster virus (VZV; chickenpox and herpes zoster) may become severe during the administration of immunosuppressants.
Caution should be exercised especially with respect to the following:
Before starting the administration of immunosuppressants, the prescriber should check to see if the patient has a history of VZV. Serologic testing may be useful in determining previous exposure. Patients who have no history of exposure should avoid contact with individuals with chickenpox or herpes zoster.
If the patient is exposed to VZV, special care must be taken to avoid patients developing chickenpox or herpes zoster, and passive immunisation with varicella- zoster immunoglobulin (VZIG) may be considered. APO-AZATHIOPRINE (Azathioprine Tablets) Page 11 of 35 If the patient is infected with VZV, appropriate measures should be taken, which may include antiviral therapy and supportive care.
Hypersensitivity Patients with a history of hypersensitivity reaction to 6-mercaptopurine should not be prescribed azathioprine. Macrophage activation syndrome Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in patients with autoimmune conditions, in particular with inflammatory bowel disease (IBD), and there could potentially be an increased susceptibility for developing the condition with the use of azathioprine.
If MAS occurs, or is suspected, evaluation and treatment should be started as early as possible, and treatment with azathioprine should be discontinued. Physicians should be attentive to symptoms of infection such as EBV and cytomegalovirus (CMV), as […]
4 Geriatrics ........................................................................................................... 13 8 ADVERSE REACTIONS ..................................................................................................
1 Adverse Reaction Overview ................................................................................... 2 Clinical Trial Adverse Reactions ............................................................................. 3 Less Common Clinical Trial Adverse Reactions ......................................................
5 Post-Market Adverse Reactions ............................................................................ 16 APO-AZATHIOPRINE (Azathioprine Tablets) Page 3 of 35 9 DRUG INTERACTIONS ..................................................................................................
4 Drug-Drug Interactions .......................................................................................... 5 Drug-Food Interactions.......................................................................................... 6 Drug-Herb Interactions ..........................................................................................
7 Drug-Laboratory Test Interactions......................................................................... 18 10 CLINICAL PHARMACOLOGY ......................................................................................... 1 Mechanism of Action.............................................................................................
2 Pharmacodynamics ............................................................................................... 3 Pharmacokinetics ..................................................................................................
19 11 STORAGE, STABILITY AND DISPOSAL ........................................................................... 21 12 SPECIAL HANDLING INSTRUCTIONS ............................................................................. 21 PART II: SCIENTIFIC INFORMATION ........................................................................................
22 13 PHARMACEUTICAL INFORMATION .............................................................................. 22 14 CLINICAL TRIALS ..........................................................................................................
1 Clinical Trial by Indication ...................................................................................... 3 Comparative Bioavailability Studies ...................................................................... 23 15 MICROBIOLOGY ..........................................................................................................
25 16 NON-CLINICAL TOXICOLOGY ....................................................................................... 25 17 SUPPORTING PRODUCT MONOGRAPHS ...................................................................... 28 PATIENT MEDICATION INFORMATION ...................................................................................
29 APO-AZATHIOPRINE (Azathioprine Tablets) Page 4 of 35 PART I: HEALTH PROFESSIONAL INFORMATION 1 INDICATIONS APO-AZATHIOPRINE (azathioprine tablets) is indicated for: • Renal Homotransplantation APO-AZATHIOPRINE is indicated as an adjunct for the prevention of rejection in renal homotransplantation.
• Rheumatoid Arthritis APO-AZATHIOPRINE is indicated only in adult patients meeting criteria for classic or definite rheumatoid arthritis as specified by the American Rheumatism Association. APO- AZATHIOPRINE should be restricted to patients with severe, active and erosive disease not responsive to conventional management including rest, acetylsalicylic acid or other non-steroidal drugs, or with […]