Imuprin

Imuprin is used as an immunosuppressant antimetabolite either alone or, more commonly, in combination with other agents (usually corticosteroids) and procedures which influence the immune response.

Therapeutic effect may be evident only after weeks or months and can include a steroid-sparing effect, thereby reducing the toxicity associated with high dosage and prolonged usage of corticosteroids.

Imuprin in combination with corticosteroids and/or other immunosuppressive agents and procedures, is indicated to enhance the survival of organ transplants, such as renal transplants, cardiac transplants, and hepatic transplants; and to reduce the corticosteroid requirements of renal transplant recipients. Imuprin either alone or more usually in combination with corticosteroids and/or other drugs and procedures has been used with clinical benefit (which may include reduction of dosage or discontinuation of corticosteroids) in a proportion of patients suffering from the following:

- severe rheumatoid arthritis - systemic lupus erythematosus

- dermatomyositis and polymyositis

- auto-immune chronic active hepatitis

- pemphigus vulgaris

- polyarteritis nodosa

- auto-immune haemolytic anaemia

- chronic refractory idiopathic thrombocytopenic purpura

Imuprin tablets are used as an immunosuppressant antimetabolite either alone or, more commonly, in combination with other agents (usually corticosteroids) and procedures which influence the immune response. Therapeutic effect may be evident only after weeks or months and can include a steroid-sparing effect, thereby reducing the toxicity associated with high dosage and prolonged usage of corticosteroids.

Imuprin, in combination with corticosteroids and/or other immunosuppressive agents and procedures, is indicated to enhance the survival of organ transplants, such as renal transplants, cardiac transplants, and hepatic transplants; and to reduce the corticosteroid requirements of renal transplant recipients.

Imuprin, either alone or more usually in combination with corticosteroids and/or other drugs and procedures, has been used with clinical benefit (which may include reduction of dosage or discontinuation of corticosteroids) in a proportion of patients suffering from the following:

severe rheumatoid arthritis;

systemic lupus erythematosus;

dermatomyositis and polymyositis;

auto-immune chronic active hepatitis;

pemphigus vulgaris;

polyarteritis nodosa;

auto-immune haemolytic anaemia;

chronic refractory idiopathic thrombocytopenic purpura.

Specialist medical literature should be consulted for guidance as to clinical experience in particular conditions.

General

When the oral route is impractical, Imuprin injection may be administered by the i.v. route only, however, this route should be discontinued as soon as oral therapy can be tolerated once more.

Posology

Imuprin should be administered at least 1 hour before or 3 hours after food or milk.

Dosage in transplantation - adults:

Depending on the immunosuppressive regime employed, a dosage of up to 5 mg/kg bodyweight/day may be given on the first day of therapy, either orally or intravenously.

Maintenance dosage should range from 1-4 mg/kg/bodyweight/day and must be adjusted according to clinical requirements and haematological tolerance.

Evidence indicates that Imuprin therapy should be maintained indefinitely, even if only low doses are necessary, because of the risk of graft rejection.

Dosage in other conditions - adults:

In general, starting dosage is from 1-3 mg/kg bodyweight/day, and should be adjusted, within these limits, depending on the clinical response (which may not be evident for weeks or months) and haematological tolerance.

When therapeutic response is evident, consideration should be given to reducing the maintenance dosage to the lowest level compatible with the maintenance of that response. If no improvement occurs in the patient's condition within 3 months, consideration should be given to withdrawing the medicinal product.

The maintenance dosage required may range from less than 1 mg/kg bodyweight/day to 3 mg/kg bodyweight/day, depending on the clinical condition being treated and the individual patient response, including haematological tolerance.

Paediatric population

Transplants: See above Dosage in transplantation - adults.

Other Indications:

Overweight children

Use in older people:

There is limited experience of the administration of Imuprin to elderly patients./or hepatic impairment).

Patients with renal and/ or hepatic impairment

In patients with renal and/or hepatic insufficiency, consideration should be given to reducing the dosage.

Drug interactions

When xanthine oxidase inhibitors, such as allopurinol, and Imuprin are administered concomitantly it is essential that only 25% of the usual dose of Imuprin is given since allopurinol decreases the rate of catabolism of Imuprin.

TPMT-deficient patients

Patients with NUDT15 variant

Patients with inherited mutated NUDT15 gene are at increased risk for severe 6-mercaptopurine toxicity (see 4.4). These patients generally require dose reduction; particularly those being NUDT15 variant homozygotes (see 4.4). Genotypic testing of NUDT15 variants may be considered before initiating 6-mercaptopurine therapy. In any case, close monitoring of blood counts is necessary.

Method of administration

For oral use.

The tablet should be taken with at least a glass of liquid (200 ml).

Precautions to be taken before handling or administering the medicinal product

Transplantation - adults and children

Depending on the immunosuppressive regimen employed, a dosage of up to 5 mg/kg body weight/day may be given on the first day of therapy, either orally or intravenously.

Maintenance dosage should range from 1 to 4 mg/kg body weight/day and must be adjusted according to clinical requirements and haematological tolerance.

Evidence indicates that Imuprin therapy should be maintained indefinitely, even if only low doses are necessary, because of the risk of graft rejection.

Dosage in other conditions - adults and children

In general, starting dosage is from 1 to 3 mg/kg body weight/day, and should be adjusted, within these limits, depending on the clinical response (which may not be evident for weeks or months) and haematological tolerance.

When therapeutic response is evident, consideration should be given to reducing the maintenance dosage to the lowest level compatible with the maintenance of that response. If no improvement occurs in the patient's condition within 3 months, consideration should be given to withdrawing Imuprin.

The maintenance dosage required may range from less than 1 mg/kg body weight/day to 3 mg/kg body weight/day, depending on the clinical condition being treated and the individual patient response, including haematological tolerance.

In patients with renal and/or hepatic insufficiency, dosages should be given at the lower end of the normal range (see Special Warnings and Precautions for Use for further details).

Use in the elderly (see Renal and/or hepatic insufficiency)

There is limited experience of the administration of Imuprin to elderly patients. Although the available data do not provide evidence that the incidence of side effects among elderly patients is higher than that among other patients treated with Imuprin, it is recommended that the dosages used should be at the lower end of the range.

Particular care should be taken to monitor haematological response and to reduce the maintenance dosage to the minimum required for clinical response.

Patients with NUDT15 variant

Patients with inherited mutated NUDT15 gene are at increased risk for severe azathioprine toxicity (see 4.4).These patients generally require dose reduction; particularly those being NUDT15 variant homozygotes (see 4.4). Genotypic testing of NUDT15 variants may be considered before initiating azathioprine therapy. In any case, close monitoring of blood counts is necessary.

Imuprin is contra-indicated in patients known to be hypersensitive to azathioprine. Hypersensitivity to 6-mercaptopurine (6-MP) should alert the prescriber to probable hypersensitivity to Imuprin.

Imuprin therapy should not be initiated in patients who may be pregnant, or who are likely to become pregnant without careful assessment of risk versus benefit (see Special Warnings and Precautions for Use and Pregnancy and Lactation).