TREOSULFAN

Posology The dosage of treosulfan as monotherapy is 5-8 g/m² The dose should be reduced to 6 g/m² or less in patients with risk factors such as pre-treatment with myelosuppressive agents or radiotherapy and reduced performance status.

The therapy should be repeated every three to four weeks. In combination with cisplatin, treosulfan should be dosed at 5 g/m², with cycles repeated every 3-4 weeks. Duration of treatment In general, 6 courses of treatment with treosulfan are given.

In the case of progressive disease and/or occurrence of non-tolerable adverse events, the treatment must be stopped. Dose modification If, following administration of treosulfan, the white cell count falls below 1,000/μl and/or the platelet count falls below 25,000/μl, the following dose must be reduced by 1 g/m².

Treatment should not be given if the white blood cell count is less than 3,500/μl or the thrombocyte count less than 100,000/μl after three weeks. A repeat blood count should be made after a week’s interval, when treatment may be restarted if haematological parameters are satisfactory.

If the values after this are still unchanged, the treosulfan dose must be reduced to 6 g/m² in case of monotherapy and to 3 g/m² in combination with cisplatin. If during treatment the white cell count does not fall below 3,500/μl and/or the platelet count does not fall below 100,000/μl, the dose in the following course of treatment may be increased by 1 g/m².

Elderly patients and patients with renal impairment Treosulfan is renally excreted. Blood counts should be carefully monitored in elderly and renally impaired patients and the dose adjusted accordingly. Paediatric population Treosulfan is not recommended for use in children.

Method of administration Treosulfan should be administered by intravenous infusion over 15 to 30 minutes. 6.

Summary of the safety profile The most commonly reported undesirable effects are myelosuppression and gastrointestinal complaints. These are usually mild and resolve after therapy with treosulfan. Bone marrow suppression is the dose-limiting side effect of treosulfan.

Tabulated list of adverse reactions Frequency 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), not known (cannot be estimated from the available data) Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

3% of 553 patients) who developed acute non-lymphatic leukemia during long-term treatment with oral treosulfan. The risk depended on the cumulative treosulfan dose. The spontaneous reporting system also reported isolated cases of the occurrence of myeloma, myeloproliferative disease or myelodysplastic syndromes after treosulfan therapy.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App store.

Risk of infections The risk of infections (mycotic, viral, bacterial) is increased. Haematological effects and monitoring of blood count The dose-limiting side effect of treosulfan is myelosuppression, which is usually reversible. It is manifested by a reduction in leukocytes and platelets and a decrease in haemoglobin.

The leukocytes and platelets usually reach their baseline level after 28 days. As the inhibition of bone marrow function is cumulative, the blood count should be monitored at shorter intervals starting with the third course of treatment.

This is especially important if treosulfan is combined with other forms of therapy that suppress bone marrow function such as radiotherapy. 4% of 553 patients) developed an acute non-lymphocytic leukaemia. The risk was depending on the cumulative dose of treosulfan.

Single cases of myeloma, myeloproliferative disorder and myelodysplastic syndrome have additionally been reported. Cardiac toxicity It cannot be ruled out that one case of cardiomyopathy was related to treosulfan. Pulmonary toxicity If allergic alveolitis or pulmonary fibrosis develop treosulfan should be permanently discontinued.

Risk of haemorrhagic cystitis Due to the possible development of a haemorrhagic cystitis, patients are advised to drink more fluids for up to 24 hours after intravenous infusion. 2). Use with live vaccines Cytostatic therapy may increase the risk of generalised infection after immunisation using live vaccines.

Therefore, live vaccines should not be used in patients receiving treosulfan. Extravasation During infusion, care must be taken to use a flawless technique, since painful inflammatory reactions may occur as a result of extravasation of treosulfan solution into surrounding tissue.

If extravasation does occur, the infusion should be stopped immediately and any remaining dose should be administered into another vein. Prevention of pregnancy Women of childbearing potential have to use effective contraception during treatment and for the first six months after treatment.

Hypersensitivity to the active substance. Severe and lasting bone marrow depression. 6).