Treosulfan parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Injections of treosulfan
Drugs List
Therapeutic Indications
Uses
Conditioning prior to allogeneic haematopoietic stem cell transplant
Treatment of carcinoma of the ovary
Treatment of all types of ovarian cancer either supplementary to surgery or palliatively.
Conditioning treatment prior to allogeneic haematopoietic stem cell transplantation (alloHSCT) in adults with maligant and non-malignant disease, and in paediatric patients older than one month with malignant diseases.
Uncontrolled studies have shown treosulfan may be useful in other refractory neoplasms.
Dosage
Adults
Ovarian cancer
3 to 8 grams/metre square intravenously every 1 to 3 weeks, depending on blood counts and concurrent chemotherapy.
Lower doses should be given if used in combination with other cytotoxics or radiotherapy.
Single injections of up to 8 grams/metre squared have been given with no serious adverse effects.
Doses up to 1.5 gram/metre squared have been given intraperitoneally.
Conditioning treatment prior to alloHSCT
Adults with malignant disease in combination with fludarabine
10 grams/metre square body surface area (BSA) per day, on 3 consecutive days (day -4, -3, -2) before stem cell infusion (day 0).
Fludarabine 30mg/metre square body surface area (BSA) per day, on 5 consecutive days (day -6, -5, -4, -3, -2) before stem cell infusion (day 0).
Treosulfan dose should be administered before fludarabine dose on days -4, -3, -2.
Adults with non-malignant disease in combination with fludarabine with or without thiotepa
14 grams/metre square body surface area (BSA) per day, on 3 consecutive days (day -6, -5, -4) before stem cell infusion (day 0).
Fludarabine 30mg/metre square body surface area (BSA) per day, on 5 consecutive days (day -7, -6, -5, -4, -3) before stem cell infusion (day 0).
Treosulfan dose should be administered before fludarabine dose on days -6, -5, -4.
Thiotepa 5mg/kg twice a day, on day -2 before stem cell infusion (day 0).
Children
Conditioning treatment prior to alloHSCT
Children over 1 month with malignant disease in combination with fludarabine with or without thiotepa
10-14 grams/metre square body surface area (BSA) per day, on 3 consecutive days (day -6, -5, -4) before stem cell infusion (day 0).
The dose of treosulfan should be adapted to the patient's BSA as follows:
Body surface area less than 0.5 metres square: 10 grams/metre square
Body surface area between 0.5 and 1 metres square: 12 grams/metre square
Body surface area greater than 1 metres square: 14 grams/metre square
Fludarabine 30mg/metre square body surface area (BSA) per day, on 5 consecutive days (day -7, -6, -5, -4, -3) before stem cell infusion (day 0).
Treosulfan dose should be administered before fludarabine dose on days -6, -5, -4.
Thiotepa 5mg/kg twice a day, on day -2 before stem cell infusion (day 0).
Patients with Renal Impairment
Ovarian cancer
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
Ovarian cancer
Suspend treatment if white blood cell count is less than 3.5 x 10 to the power 9/L or platelet count is less than 100 x 10 to the power 9/L, repeat blood count after 1 week. Treatment can be restarted if haematological parameters are satisfactory.
Administration
Ovarian cancer
To be given intravenously, either as a bolus or as an infusion.
Doses up to 3 grams/metre squared may be given as a bolus injection.
Doses up to 1.5 grams/metre squared can be give intraperitoneally.
Larger doses should be given as an intravenous infusion at a rate of 3 grams/metre squared every 5 to 10 minutes (8 grams/metre squared as a 30 minute infusion).
Conditioning treatment prior to alloHSCT
To be given by intravenous infusion only.
Contraindications
Breastfeeding
Children under 18 years - if treating ovarian cancer
Fanconi's anaemia - if used as conditioning treatment prior to alloHSCT
Leucocyte count below 3.5x10 to the power of 9/L-if treating ovarian cancer
Neonates under 1 month -if used as conditioning treatment prior to alloHSCT
Platelet count below 100x10 to the power of 9/L- if treating ovarian cancer
Pregnancy
Severe cardiac impairment - if conditioning treatment before alloHSCT
Severe hepatic impairment-if used as conditioning treatment before alloHSCT
Severe myelosuppression - if treating ovarian cancer
Severe renal impairment-if used as conditioning treatment prior to alloHSCT
Severe respiratory impairment - if conditioning treatment prior to alloHSCT
Uncontrolled systemic infection - if conditioning treatment before alloHSCT
Precautions and Warnings
Elderly - if treating ovarian cancer
Porphyria
Renal impairment - if treating ovarian cancer
Administration of live vaccines is not recommended
Advise patient ability to drive or operate machinery may be impaired
Conditioning prior to alloHSCT: Consider use of anti-infective prophylaxis
Conditioning prior to alloHSCT: Consider use of mucositis prophylaxis
Give pre-treatment counselling and consideration of sperm cryopreservation
Not all available brands are licensed for all age groups
Not all available brands are licensed for all indications
Treatment to be prescribed under the supervision of a specialist
Avoid contact with skin and mucous membranes
Consult local policy on the safe use of anti-cancer drugs
If extravasation occurs follow local policy & seek expert help immediately
Ovarian cancer: Ensure patient has adequate fluid intake
Staff: Not to be handled by pregnant staff
Conditioning prior to alloHSCT: Monitor neurological function in < 4 years
Conditioning prior to alloHSCT: Monitor respiratory function in < 1 year
Monitor full blood count regularly
Conditioning prior to alloHSCT: Consider G-CSF in severe neutropenia
Conditioning prior to alloHSCT:Menstruation may stop in premenopausal women
Increased risk of myelodysplastic syndrome & non-lymphocytic leukaemia
Oversuppression of immune system may increase susceptibility to infection
Potentially mutagenic and carcinogenic
Ovarian cancer: Discontinue if pulmonary toxicity occurs
Ovarian cancer: Suspend treatment if platelets fall below 100,000/cubic mm
Ovarian cancer: Suspend treatment if WBC count falls below 3500/cubic mm
May cause impaired fertility
Female: Contraception required during and for 6 months after treatment
Male: Contraception required during and for 6 months after treatment
Avoid inhalation of the product
Conditioning prior to alloHSCT: Advise on high oral hygiene standards
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 during pregnancy.
Use of treosulfan during pregnancy is contraindicated by the manufacturer. 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.
Lactation
Treosulfan is contraindicated during breastfeeding
Use of treosulfan during breastfeeding is contraindicated by the manufacturer. At the time of writing it is unknown whether treosulfan is excreted in human breast milk, a risk to neonates cannot be excluded.
Side Effects
Abdominal distension
Abdominal pain
Acidosis
Acute kidney injury
Agitation
Allergic alveolitis
Allergic reaction
Alopecia
Anaemia
Arrhythmias
Arthralgia
Asthenia
Atrial fibrillation
Back pain
Bone pain
Cardiomyopathy
Chills
Confusion
Constipation
Cough
Decreased appetite
Dermatitis acneiform
Diarrhoea
Dizziness
Dry mouth
Dyspepsia
Dysphagia
Dyspnoea
Epistaxis
Erythema
Erythema multiforme
Exacerbation of Addison's disease
Exacerbation of psoriasis
Fatigue
Febrile neutropenia
Flushing
Gamma glutamyl transferase (GGT) increased
Gastritis
Gastro-intestinal pain
Haematoma
Haematuria
Haemorrhagic cystitis
Headache
Hepatic veno-occlusive disease
Hepatotoxicity
Hiccups
Hyperglycaemia
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypoglycaemia
Hypotension
Increase in alkaline phosphatase
Increase in serum transaminases
Infections
Influenza-like syndrome
Insomnia
Laryngeal discomfort
Laryngeal swelling
Lethargy
Leukopenia
Maculopapular rash
Mouth haemorrhage
Mucositis
Multiple myeloma
Myalgia
Myelodysplastic syndrome
Myelosuppression
Nausea
Necrosis (injection site)
Non-lymphocytic leukaemia (acute)
Oedema
Oral pain
Pain on injection
Painful extremities
Palmar-Plantar Erythrodysaesthesia syndrome
Pancytopenia
Paraesthesia
Peripheral sensory neuropathy
Pharyngitis
Pleural effusion
Pneumonia
Pneumonitis
Pruritus
Pulmonary fibrosis
Purpura
Pyrexia
Raised C-reactive protein
Rash
Scleroderma
Sepsis
Serum bilirubin increased
Sinus arrhythmia
Skin pigmentation changes
Stomatitis
Thrombocytopenia
Urticaria
Vomiting
Weight gain
Weight loss
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 ( https://www.toxbase.org/ ) or if this is unavailable at the backup site ( https://www.TOXBASEbackup.org/ ).
Further Information
Last Full Review Date: May 2020
Reference Sources
Summary of Product Characteristics. Treosulfan Injection. Medac GmbH. Revised December 2016.
Summary of Product Characteristics. Trecondi powder for solution for infusion. Medac GmbH. Revision date unknown.
The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
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