PURI-NETHOL Tablet Ref.[49828] Active ingredients: Mercaptopurine

Posology

Mercaptopurine monohydrate treatment should be supervised by a physician or other healthcare professional experienced in the management of patients with ALL and APL (AML M3).

Mercaptopurine monohydrate may be taken with food or on an empty stomach, but patients should standardise the method of administration. The dose should not be taken with milk or dairy products (see section 4.5). Mercaptopurine monohydrate should be taken at least 1 hour before or 2 hours after milk or dairy products.

Special Populations

Adults and paediatric population

For adults and children the usual dose is 2.5 mg/kg bodyweight per day, or 50 to 75mg/m² body surface area per day, but the dose and duration of administration depend on the nature and dosage of other cytotoxic agents given in conjunction with mercaptopurine monohydrate.

The dosage should be carefully adjusted to suit the individual patient.

Mercaptopurine monohydrate has been used in various combination therapy schedules for acute leukaemia and the literature and current treatment guidelinesshould be consulted for details.

Studies carried out in children with acute lymphoblastic leukaemia suggested that administration of mercaptopurine monohydrate in the evening lowered the risk of relapse compared with morning administration.

Older population

It is advisable to monitor renal and hepatic function in these patients, and if there is impairment, consideration should be given to reducing the mercaptopurine monohydrate dosage.

Renal impairment

Consideration should be given to reducing the dosage in patients with impaired renal function (see Section 5.2 Pharmacokinetic properties: Special patient populations; Renal impairment).

Hepatic impairment

Consideration should be given to reducing the dosage in patients with impaired hepatic function (see Section 5.2 Pharmacokinetic properties: Special patient populations; Hepatic impairment).

Medicinal product interactions

When the xanthine oxidase inhibitors allopurinol oxipurinol or thiopurinol and mercaptopurine monohydrate are administered concomitantly it is essential that only 25 % of the usual dose of mercaptopurine monohydrate is given since these agents decrease the rate of catabolism of mercaptopurine monohydrate. Concomitant administration of other xanthine oxidase inhibitors, such as febuxostat, should be avoided (see Section 4.5 Interaction with other medicinal products and other forms of interactions).

TPMT-deficient patients

Patients with inherited little or no thiopurine S-methyltransferase (TPMT) activity are at increased risk for severe mercaptopurine monohydrate toxicity from conventional doses of mercaptopurine monohydrate and generally require substantial dose reduction. The optimal starting dose for homozygous deficient patients has not been established. Most patients with heterozygous TPMT deficiency can tolerate recommended mercaptopurine monohydrate doses, but some may require dose reduction (see Section 4.4 Special warnings and precautions for use: Monitoring and Section 5.2 Pharmacokinetic properties).

Patients with NUDT15 variant

Patients with inherited mutated NUDT15 gene are at increased risk for severe mercaptopurine monohydrate 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 mercaptopurine monohydrate therapy. In any case, close monitoring of blood counts is necessary.

Symptoms and signs

Gastro-intestinal effects, including nausea, vomiting and diarrhoea and anorexia may be early symptoms of overdosage having occurred. The principal toxic effect is on the bone marrow, resulting in myelosuppression. Haematological toxicity is likely to be more profound with chronic overdosage than with a single ingestion of mercaptopurine monohydrate. Liver dysfunction and gastroenteritis may also occur.

The risk of overdosage is also increased when allopurinol is being given concomitantly with mercaptopurine monohydrate (see Section 4.5 Interaction with other medicinal products and other forms of interaction).

Treatment

As there is no known antidote, blood countsshould be closely monitored and general supportive measures, together with appropriate blood transfusion, instituted if necessary. Active measures (such as the use of activated charcoal) may not be effective in the event of mercaptopurine monohydrate overdose unless the procedure can be undertaken within 60 minutes of ingestion.

Further management should be as clinically indicated or as recommended by the national poisons centre, where available.

5 years.

Do not store above 25°C.

Store in the original container in order to protect from light.

Keep the container tightly closed in order to protect from moisture.

Amber glass bottle containing 25 tablets with a child resistant high density polyethylene/polypropylene closure with induction heat seal liners (IHS).

Safe handling

It is recommended that mercaptopurine monohydrate tablets should be handled following the prevailing local recommendations and/or regulations for the handling and disposal of cytotoxic agents.

Disposal

Any unused product or waste material should be disposed of in accordance with local requirements.