TIOGUANINE Tablet Ref.[9069] Active ingredients: Tioguanine

Posology

The exact dose and duration of administration will depend on the nature and dosage of other cytotoxic drugs given in conjunction with tioguanine.

Tioguanine is variably absorbed following oral administration and plasma levels may be reduced following emesis or intake of food.

Tioguanine can be used at various stages of treatment in short term cycles. However it is not recommended for use during maintenance therapy or similar long-term continuous treatments due to the high risk of liver toxicity (see section 4.4).

Adults

The usual dosage of tioguanine is between 100 and 200 mg/m² body surface area, per day.

Paediatric population

Similar dosages to those used in adults, with appropriate correction for body surface area, have been used.

Use in the elderly

There are no specific dosage recommendations in elderly patients (see dosage in renal or hepatic impairment).

Tioguanine has been used in various combination chemotherapy schedules in elderly patients with acute leukaemia at equivalent doses to those used in younger patients.

Special populations

Dosage in renal or hepatic impairment

Consideration should be given to reducing the dosage in patients with impaired hepatic or renal function.

TPMT-deficient patients

Patients with inherited little or no thiopurine S-methyltransferase (TPMT) activity are at increased risk for severe tioguanine toxicity from conventional doses of tioguanine 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 tioguanine doses, but some may require dose reduction. Genotypic and phenotypic tests of TPMT are available (see sections 4.4 and 5.2).

Patients with NUDT15 variant

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

Method of administration

Oral.

Symptoms

The principal toxic effect is on the bone marrow and haematological toxicity is likely to be more profound with chronic overdosage than with a single ingestion of tioguanine.

Management

As there is no known antidote the blood picture should be closely monitored and general supportive measures, together with appropriate blood transfusion instituted if necessary. Further management should be as clinically indicated or as recommended by the national poisons center, where available.

Shelf life: 24 months (unopened).

Store below 25°C.

Keep dry.

Protect from light.

Amber glass bottles with child-resistant polyethylene/polypropylene closures.

Pack size 25.

It is recommended that the handling of Tioguanine tablets follows the “Guidelines for the handling of cytotoxic drugs” issued by the Royal Pharmaceutical Society of Great Britain Working Party on the handling of cytotoxic drugs.

If halving of a tablet is required, care should be taken not to contaminate the hands or inhale the drug.