Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Nova Laboratories Ireland Limited, 3rd Floor, Ulysses House, Foley Street, Dublin 1, D01 W2T2, Ireland
Jayempi is indicated in combination with other immunosuppressive agents for the prophylaxis of transplant rejection in patients receiving allogenic kidney, liver, heart, lung or pancreas transplants. Azathioprine is indicated in immunosuppressive regimens as an adjunct to immunosuppressive agents that form the mainstay of treatment (basis immunosuppression).
Jayempi is used as an immunosuppressant antimetabolite either alone or, more commonly, in combination with other agents (usually corticosteroids) and/or procedures which influence the immune response.
Jayempi is indicated in patients who are intolerant to glucocorticosteroids or if the therapeutic response is inadequate despite treatment with high doses of glucocorticosteroids, in the following diseases:
Jayempi is used for the treatment of moderately severe to severe forms of chronic inflammatory bowel disease (IBD) (Crohn’s disease or ulcerative colitis) in patients in whom glucocorticosteroid therapy is necessary, but where glucocorticosteroids are not tolerated, or in whom the disease is untreatable with other common means of first choice.
It is also indicated in adult patients in relapsing multiple sclerosis, if an immunomodulatory therapy is indicated but beta interferon therapy is not possible, or a stable course has been achieved with previous treatment with azathioprine.
Jayempi is indicated for the treatment of generalised myasthenia gravis. Depending on the severity of the disease, Jayempi should be given in combination with glucocorticosteroids because of slow onset of action at the beginning of treatment and the glucocorticosteroid dose should be gradually reduced after several months of treatment.
Therapy with Jayempi should be initiated by a physician experienced in the administration and monitoring of immunosuppressive medicinal products.
Depending on the immunosuppressive regime selected, a dose of up to 5 mg/kg body weight/day may be given on the first day of therapy. The maintenance dose can range from 1-4 mg/kg body weight/day and must be adjusted according to the clinical requirements and haematological tolerance.
Azathioprine therapy should be maintained indefinitely, even if only low doses are necessary, because of the risk of graft rejection.
The usual dose for the treatment of relapsing forms of multiple sclerosis is between 2 and 3 mg/kg body weight/day. A treatment duration of more than 1 year may be required until manifestation of the effect, and at least 2 years may be needed until the disease is actually under control.
The recommended dose for the treatment of myasthenia gravis is 2 mg/kg to 3 mg/kg body weight/day.
Treatment success usually occurs 2 to 6 months after the start of treatment at the earliest. Depending on the severity of the disease, Jayempi should be given in combination with glucocorticosteroids at the start of treatment because of the slow onset of the effect. The dose of glucocorticosteroids can be gradually reduced over several months.
Treatment with Jayempi should be continued for at least 2 to 3 years.
The initial dose is usually between 1.0 and 1.5 mg/kg body weight/day and the maintenance dose is up to 2 mg/kg body weight/day.
In general, the starting dose is 1 to 3 mg/kg body weight/day and should be adjusted according to 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 dose to the lowest level compatible with the maintenance of that response. If no improvement occurs in the patient’s condition within 3 to 6 months, consideration should be given to withdrawing the medicinal product.
The maintenance dose 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.
However, in patients with IBD, a treatment duration of at least 12 months should be considered, whereby a response to treatment may only be recognisable clinically after three to four months.
With concomitant use of xanthine oxidase inhibitors such as allopurinol, oxipurinol and thiopurinol, the dose of azathioprine should be reduced to a quarter of the normal dose, because allopurinol, oxipurinol and thiopurinol reduce the metabolism of azathioprine (see section 4.5).
The table below shows, for a range of age, weight and doses, the dose (mg) to volume (ml) conversion using the two oral syringes.
Table 1. Dose (mg) to volume (ml) conversion using the two oral syringes:
| Age (Years) | Weight* (Kg) | Dose† | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1mg/kg | 2mg/kg | 3mg/kg | 4mg/kg | 5mg/kg | |||||||
| mg | ml | mg | ml | mg | ml | mg | ml | mg | ml | ||
| 0 | 3.3 | 3.3 | 0.3 | 6.6 | 0.7 | 9.9 | 1.0 | 13.2 | 1.3 | 16.5 | 1.7 |
| 1 month | 4.5 | 4.5 | 0.5 | 9.0 | 0.9 | 13.5 | 1.4 | 18.0 | 1.8 | 22.5 | 2.3 |
| 2 month | 5.6 | 5.6 | 0.6 | 11.2 | 1.1 | 16.8 | 1.7 | 22.4 | 2.2 | 28.0 | 2.8 |
| 3 month | 6.4 | 6.4 | 0.6 | 12.8 | 1.3 | 19.2 | 1.9 | 25.6 | 2.6 | 32.0 | 3.25 |
| 4 month | 7.0 | 7.0 | 0.7 | 14.0 | 1.4 | 21.0 | 2.1 | 28.0 | 2.8 | 35.0 | 3.50 |
| 5 month | 7.5 | 7.5 | 0.8 | 15.0 | 1.5 | 22.5 | 2.3 | 30.0 | 3.0 | 37.5 | 3.75 |
| 6 month | 7.9 | 7.9 | 0.8 | 15.8 | 1.6 | 23.7 | 2.4 | 31.6 | 3.25 | 39.5 | 4.00 |
| 1.0 | 9.6 | 9.6 | 1.0 | 19.2 | 1.9 | 28.8 | 2.9 | 38.4 | 3.75 | 48.0 | 4.75 |
| 1.5 | 10.9 | 10.9 | 1.1 | 21.8 | 2.2 | 32.7 | 3.25 | 43.6 | 4.25 | 54.5 | 5.50 |
| 2.0 | 12.2 | 12.2 | 1.2 | 24.4 | 2.4 | 36.6 | 3.75 | 48.8 | 5.00 | 61.0 | 6.00 |
| 3.0 | 14.3 | 14.3 | 1.4 | 28.6 | 2.9 | 42.9 | 4.25 | 57.2 | 5.75 | 71.5 | 7.25 |
| 4.0 | 16.3 | 16.3 | 1.6 | 32.6 | 3.25 | 48.9 | 5.00 | 65.2 | 6.50 | 81.5 | 8.25 |
| 5.0 | 18.3 | 18.3 | 1.8 | 36.6 | 3.75 | 54.9 | 5.50 | 73.2 | 7.25 | 91.5 | 9.25 |
| 6.0 | 20.5 | 20.5 | 2.1 | 41.0 | 4.00 | 61.5 | 6.25 | 82.0 | 8.25 | 102.5 | 10.25 |
| 7.0 | 22.9 | 22.9 | 2.3 | 45.8 | 4.50 | 68.7 | 7.00 | 91.6 | 9.25 | 114.5 | 11.50 |
| 8.0 | 25.4 | 25.4 | 2.5 | 50.8 | 5.00 | 76.2 | 7.50 | 101.6 | 10.25 | 127.0 | 12.75 |
| 9.0 | 28.1 | 28.1 | 2.8 | 56.2 | 5.50 | 84.3 | 8.50 | 112.4 | 11.25 | 140.5 | 14.00 |
| 10.0 | 31.2 | 31.2 | 3.0 | 62.4 | 6.25 | 93.6 | 9.25 | 124.8 | 12.50 | 156.0 | 15.50 |
| 12.0 | 38.2 | 38.2 | 3.75 | 76.4 | 7.75 | 114.6 | 11.50 | 152.8 | 15.25 | 191.0 | 19.00 |
| 15.0 | 55.5 | 55.5 | 5.50 | 111.0 | 11.00 | 166.5 | 16.75 | 222.0 | 22.25 | 277.5 | 27.75 |
| 18.0 | 67.0 | 67.0 | 6.75 | 134.0 | 13.50 | 201.0 | 20.00 | 268.0 | 26.75 | 335.0 | 33.50 |
* 50th percentile for boys extracted from WHO (0-10 years) and UK (11-18 years) growth charts
† Doses less than or equal to 30 mg to be drawn up using the 3 ml (red) oral syringe with 0.1 ml (1mg) graduations. Doses greater than 30 mg to be drawn up using the 12 ml (white) oral syringe with 0.25 ml (2.5mg) graduations (shaded cells).
Transplantation: The posology in paediatric population is the same as in adults.
Myasthenia gravis: The posology in paediatric population is the same as in adults.
Chronic active auto-immune hepatitis: The posology in paediatric population is the same as in adults.
Dose in other conditions: The posology in paediatric population is the same as in adults.
Juvenile idiopathic arthritis: The safety and efficacy of Jayempi in children (0 to 16 years) have not yet been established. No data are available.
Multiple sclerosis:
There is no relevant use of Jayempi in the paediatric population for the indication of multiple sclerosis.
Children considered to be overweight may require doses at the higher end of the dose range. Therefore, close monitoring of response to treatment is recommended (see section 5.2).
It is recommended to monitor the kidney and liver function and reduce the dose in the case of impaired function (see section 4.2). The dose used should be at the lower end of the normal range. For controls of blood count, see section 4.4.
In patients with hepatic and/or renal impairment the dose should be reduced to the lower end of the normal range (see section 4.4).
Patients with inherited little or no thiopurine S-methyltransferase (TPMT) activity are at increased risk for severe azathioprine toxicity from conventional doses of azathioprine and generally require substantial dose reduction. The optimal starting dose for homozygous deficient patients has not been established (see sections 4.4 and 5.2).
Most patients with heterozygous TPMT deficiency can tolerate recommended azathioprine doses, but some may require dose reduction. Genotypic and phenotypic tests of TPMT are available (see sections 4.4 and 5.2).
Patients with inherited mutated NUDT15 gene are at increased risk for severe azathioprine toxicity (see section 4.4). These patients generally require dose reduction; particularly those being NUDT15 variant homozygotes. Genotypic testing of NUDT15 variants may be considered before initiating azathioprine therapy. In any case, close monitoring of blood counts is necessary (see section 4.4).
Jayempi is for oral use and requires redispersing by shaking prior to dosing.
To measure the dose in ml in accordance with the prescribed posology, two oral syringes are included in the pack; 3 ml (with red plunger) and 12 ml (with white plunger). The oral syringes are graduated in 0.1 ml (1 mg) and 0.25 ml (2.5 mg) steps respectively.
The healthcare professional should advise the patient or carer which syringe to use to ensure that the correct volume is administered.
In adults without swallowing difficulties, solid oral formulations may be more appropriate and convenient.
Jayempi should be taken at least 1 hour before or 2 hours after a meal or milk.
Water should be taken after each dose in order to ensure accurate and consistent dose delivery to the stomach.
The most common effect of overdose with azathioprine is myelosuppression with blood count disorders, which may be maximal after 9 to 14 days. The main symptoms of myelosuppression are mouth and throat ulceration, bruising, fever of unknown aetiology and unexplained infection. Furthermore, spontaneous bleeding and extreme fatigue may occur. These symptoms are more likely to present following prolonged mild overdose, rather than after a single acute overdose. A case of a patient who ingested a single dose of 7.5 g azathioprine has been reported. Acute symptoms included nausea, vomiting and diarrhoea, followed by moderate leucopenia and mild impairment of the liver function. Recovery was without sequelae.
Since there is no specific antidote, the blood count should be closely monitored, appropriate symptomatic treatment should be initiated, where necessary, and the appropriate blood transfusions be administered. In the case of overdose, active measures (such as use of activated charcoal) will probably only be effective if they are carried out within 60 minutes of ingestion.
Azathioprine is partially dialysable. Nevertheless, the benefit of dialysis in patients who have taken an overdose is not known.
2 years.
After first opening: 12 weeks.
Do not store above 25°C.
Keep the bottle tightly closed (see section 6.6).
Amber type III glass bottle with tamper evident child-resistant closure (HDPE with expanded polyethylene liner) containing 200 ml of oral suspension.
Each pack contains one bottle, an HDPE bottle adaptor, a 3 mL polyethylene oral dosing syringe with red plunger (0.1 mL dose graduations) and a 12 mL polyethylene oral dosing syringe with white plunger (0.25 mL dose graduations).
Anyone handling Jayempi should wash their hands before and after administering a dose. To decrease the risk of exposure, parents and care givers should wear disposable gloves when handling Jayempi.
Contact with skin or mucous membrane must be avoided. If Jayempi comes into contact with skin or mucosa, it should be washed immediately and thoroughly with soap and water. Spillages must be wiped immediately.
Women who are pregnant, planning to be or breast-feeding should not handle Jayempi.
Parents/care givers and patients should be advised to keep Jayempi out of the sight and reach of children, preferably in a locked cupboard. Accidental ingestion can be lethal for children.
Keep the bottle tightly closed to protect the integrity of the medicinal product and minimise the risk of accidental spillage. The bottle should be shaken to ensure the oral suspension is well mixed.
Jayempi is cytotoxic. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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