Treosulfan capsules
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of treosulfan
Drugs List
Therapeutic Indications
Uses
Treatment of carcinoma of the ovary
Treatment of all types of ovarian cancer either supplementary to surgery or palliatively.
Uncontrolled studies have shown treosulfan may be useful in other refractory neoplasms.
Dosage
For use only by physicians experienced in cancer chemotherapy
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
Total dose of 21 g to 28 g in the initial 8 weeks.
The following regimes have been indicated:
Regimen A:
1 g daily in four divided doses for 4 weeks followed by 4 weeks off therapy.
Regimen B:
1 g daily in four divided doses for 2 weeks followed by 2 weeks off therapy.
Regimen C:
1.5 g daily in three divided doses for 1 week, followed by 3 weeks off therapy. If no evidence of haematological toxicity at this dose in this regimen, increase to 2 g daily in four divided doses for one week for the second and subsequent courses.
The cycles should be repeated with the dose being adjusted if necessary according to the effect on the peripheral blood counts.
Elderly
(See Dosage; Adult)
Patients with Renal Impairment
The renal drug handbook suggests the following dose reductions:
Creatinine clearance greater than or equal to 30 ml/minute: Dose as normal.
Creatinine clearance less than 30 ml/minute: Reduce dose by 60%
Additional Dosage Information
Present evidence suggests regimens B and C are less myelosuppressive than regimen A, whilst retaining maximum cytotoxic efficacy.
Dose modifications
Suspend treatment if white blood cell count is less than 3 x 10 to the power 9/L and/or platelet count is less than 100 x 10 to the power 9/L, repeat blood count after 1 to 2 weeks. Treatment can be restarted if haematological parameters are satisfactory, reducing dose as follows:
Regimen A: Reduce from 1 g daily for 4 weeks to 0.75 g daily for 4 weeks and, if necessary, to 0.5 g daily for 4 weeks
Regimen B: Reduce from 1 g daily for 2 weeks to 0.75 g for 2 weeks and, if necessary, to 0.5 g daily for 2 weeks
Regimen C: Reduce from 2 g daily for 1 week to 1.5 g daily for 1 week and, if necessary, to 1 g daily for 1 week
Contraindications
Children under 18 years
Leucocyte count below 3 x 10 to the power of 9 / L
Platelet count below 100 x 10 to the power of 9/ L
Breastfeeding
Pregnancy
Severe myelosuppression
Precautions and Warnings
Elderly
Porphyria
Renal impairment - creatinine clearance below 30 ml/minute
Administration of live vaccines is not recommended
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Ensure patient has adequate fluid intake
Staff: Not to be handled by pregnant staff
Monitor full blood count regularly
Advise patient to report signs or symptoms of cystitis
Increased risk of myelodysplastic syndrome & non-lymphocytic leukaemia
Oversuppression of immune system may increase susceptibility to infection
Reduce dose in patients with haematological toxicity
Discontinue if pulmonary toxicity occurs
Suspend treatment if leukocyte count falls below 3000/microlitre
Suspend treatment if platelets fall below 100,000/cubic mm
Female: Ensure adequate contraception during treatment
Blood counts usually reach their baseline level after 28 days. As bone marrow suppression is cumulative, blood counts should be monitored at shorter intervals from the 3rd treatment cycle onwards.
Pregnancy and Lactation
Pregnancy
Treosulfan is contraindicated in pregnancy.
At the time of writing there is no published experience concerning the use of treosulfan during pregnancy. Like other cytostatic agents with alkylating properties, treosulfan has a mutagenic potential and therefore should not be given during pregnancy.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Treosulfan is contraindicated in breastfeeding
At the time of writing it is unknown whether treosulfan is excreted in human breast milk, a risk to neonates cannot be excluded.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Allergic alveolitis
Allergic reaction
Alopecia
Anaemia
Cardiomyopathy
Erythema
Exacerbation of Addison's disease
Exacerbation of psoriasis
Haemorrhagic cystitis
Hypoglycaemia
Influenza-like syndrome
Leukopenia
Multiple myeloma
Myelodysplastic syndrome
Nausea
Non-lymphocytic leukaemia (acute)
Pancytopenia
Paraesthesia
Pneumonia
Pulmonary fibrosis
Scleroderma
Skin pigmentation changes
Stomatitis
Thrombocytopenia
Urticaria
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: August 2015
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 3 August 2015.
Summary of Product Characteristics. Treosulfan Capsules 250mg. Medac GmbH. Revised January 2015.
The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
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