JAYEMPI

Therapy with Jayempi should be initiated by a physician experienced in the administration and monitoring of immunosuppressive medicinal products. Posology Transplantation 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.

Multiple sclerosis (adults only) 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.

Myasthenia gravis 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. 5 mg/kg body weight/day and the maintenance dose is up to 2 mg/kg body weight/day. Dose in other conditions 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.

Summary of the safety profile The most important adverse reactions include bone marrow depression, most frequently expressed as leukopenia and thrombocytopenia; viral, fungal and bacterial infections; life-threatening liver injury; hypersensitivity, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Tabulated list of adverse reactions The adverse reactions are listed below according to system organ class and frequency. The frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) (including isolated cases), not known (cannot be estimated from the available data).

4) Neoplasms benign, malignant and unspecified (incl. 4). 4). The increased risk of developing non-Hodgkin’s lymphomas in immunosuppressed rheumatoid arthritis patients compared with the general population appears to be related at least in part to the disease itself.

There have been rare reports of acute myeloid leucaemia and myelodysplasia (some in association with chromosomal abnormalities). Blood and lymphatic system disorders The most common adverse reaction of azathioprine is a dose-related, generally reversible, depression of bone marrow function, most frequently expressed as leucopenia, but also sometimes as thrombocytopenia and anaemia, and rarely as agranulocytosis, pancytopenia and aplastic anaemia.

5). Reversible, dose-related macrocytosis and increase in red cell haemoglobin content have occurred in association with azathioprine therapy. Megaloblastic bone marrow changes have also been observed but severe megaloblastic anaemia and erythroid hypoplasia are rare.

Immune system disorders Several different clinical syndromes, which appear to be idiosyncratic manifestations of hypersensitivity, have been described occasionally following administration of azathioprine. Clinical features include general malaise, dizziness, nausea, vomiting, diarrhoea, fever, rigors, exanthema, erythema nodosum, vasculitis, myalgia, arthralgia, hypotension, cardiac dysfunction, renal dysfunction, hepatic dysfunction and cholestasis.

4. 4). Patients with TPMT deficiency 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.

2). Most patients with heterozygous TPMT deficiency can tolerate recommended azathioprine doses, but some may require dose reduction. 2). 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. 4). Method of administration 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 and 10 ml.

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. 1. 6). 4 Special warnings and precautions for use Monitoring Therapy with Jayempi in pre-existing, severe infections, in severe disorders of the liver and bone marrow function and in the presence of pancreatitis should only be initiated subject to a careful benefit/risk analysis and the precautions specified below.

Special attention should be given to monitoring the blood count. If necessary, the maintenance dose should be reduced as much as possible, provided there is clinical response. Azathioprine should only be prescribed if the patient can be adequately monitored for haematological and hepatic effects throughout the duration of therapy.

1. 6).