Thiotepa infusion
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions of thiotepa
Drugs List
Therapeutic Indications
Uses
Conditioning prior to haematopoietic progenitor cell transplantation
Treatment in combination with other chemotherapy medicinal products, with or without total body irradiation, as conditioning treatment prior to allogenic or autologous haematopoietic progenitor cell transplantation (HPCT) in haematological diseases.
Treatment in combination with other chemotherapy medicinal products, when high dose chemotherapy with HPCT support is appropriate for the treatment of solid tumours.
Dosage
Treatment should only be administered by clinicians familiar with the use of cytotoxic drugs.
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
Autologous HPCT
Haematological Diseases and Lymphoma
Recommended dose ranges from 125 mg/metre squared/day (3.38 mg/kg/day) to 300 mg/metre squared/day (8.1 mg/kg/day) as a single daily infusion, administered from 2 up to 4 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products.
Total cumulative dose should not exceed 900 mg/metre squared (24.32 mg/kg).
Central Nervous System Lymphoma
Recommended dose is 185 mg/metre squared/day (5 mg/kg/day) as a single daily infusion, administered for 2 consecutive days before autologous HPCT.
Total cumulative dose should not exceed 370 mg/metre squared (10 mg/kg).
Multiple Myeloma
Recommended dose ranges from 150 mg/metre squared/day (4.05 mg/kg/day) to 250 mg/metre squared/day (6.76 mg/kg/day) as a single daily infusion, administered for 3 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products.
Total cumulative dose should not exceed 750 mg/metre squared (20.27 mg/kg).
Solid tumours
Recommended dose ranges from 120 mg/metre squared/day (3.24 mg/kg/day) to 250 mg/metre squared/day (6.76 mg/kg/day) as 1 or 2 divided daily infusions, administered from 2 up to 5 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products.
Total cumulative dose should not exceed 800 mg/metre squared (21.62 mg/kg).
Breast Cancer
Recommended dose ranges from 120 mg/metre squared/day (3.24 mg/kg/day) to 250 mg/metre squared/day (6.76 mg/kg/day) a single daily infusion, administered from 3 up to 5 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products.
Total cumulative dose should not exceed 800 mg/metre squared (21.62 mg/kg).
Central Nervous System Tumours
Recommended dose ranges from 125 mg/metre squared/day (3.38 mg/kg/day) to 250 mg/metre squared/day (6.76 mg/kg/day) as 1 or 2 divided daily infusions, administered from 3 up to 4 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products.
Total cumulative dose should not exceed 750 mg/metre squared (20.27 mg/kg).
Ovarian Cancer
Recommended dose is 250 mg/metre squared/day (6.76mg/kg/day) as a single daily infusion, administered for 2 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products.
Total cumulative dose should not exceed 500 mg/metre squared (13.51 mg/kg)
Germ Cell Tumours
Recommended dose ranges from 150 mg/metre squared/day (4.05 mg/kg/day) to 250 mg/metre squared/day (6.76 mg/kg/day) as a single daily infusion, administered for 3 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products.
Total cumulative dose should not exceed 750 mg/metre squared (20.27 mg/kg).
Allogenic HPCT
Haematological diseases and Leukaemia
Recommended dose ranges from 185 mg/metre squared/day (5 mg/kg/day) to 481 mg/metre squared/day (13 mg/kg/day) divided in 1 or 2 daily infusions, administered from 1 up to 3 consecutive days before allogenic HPCT depending on the combination with other chemotherapeutic medicinal products.
Total cumulative dose should not exceed 555 mg/metre squared (15 mg/kg).
Lymphoma and Thalassaemia
Recommended dose is 370 mg/metre squared/day (10 mg/kg/day) divided in 2 daily infusions, administered before allogenic HPCT depending on the combination with other chemotherapeutic medicinal products.
Total cumulative dose should not exceed 370 mg/metre squared (10 mg/kg).
Multiple Myeloma
Recommended dose is 185 mg/metre squared/day (5 mg/kg/day) as a single daily infusion, administered before allogenic HPCT.
Total cumulative dose should not exceed 185mg/metre squared (5mg/kg).
Elderly
(See Dosage; Adult)
Children
Autologous HPCT
Solid tumours
Recommended dose ranges from 150 mg/metre squared/day (6 mg/kg/day) to 350 mg/metre squared/day (14 mg/kg/day) as a single daily infusion, administered from 2 up to 3 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products.
Total cumulative dose should not exceed 1050 mg/metre squared (42 mg/kg).
Central Nervous System Tumours
Recommended dose ranges from 250 mg/metre squared/day (10 mg/kg/day) to 350 mg/metre squared/day (14 mg/kg/day) as a single daily infusion, administered for 3 consecutive days before autologous HPCT depending on the combination with other chemotherapeutic medicinal products.
Total cumulative dose should not exceed 1050 mg/metre squared (42 mg/kg).
Allogenic HPCT
Haematological diseases
Recommended dose ranges from 125 mg/metre squared/day (5mg/kg/day) to 250 mg/metre squared/day (10 mg/kg/day) divided in 1 or 2 daily infusions, administered from 1 up to 3 consecutive days before allogenic HPCT depending on the combination with other chemotherapeutic medicinal products.
Total cumulative dose should not exceed 375 mg/metre squared (15 mg/kg).
Leukaemia and Sickle Cell Anaemia
Recommended dose ranges from 250 mg/metre squared/day (10 mg/kg/day) divided in 2 daily infusions, administered before allogenic HPCT
Total cumulative dose should not exceed 250 mg/metre squared (10 mg/kg).
Thalassaemia
Recommended dose ranges from 200 mg/metre squared/day (8 mg/kg/day) to 250 mg/metre squared/day (10 mg/kg/day) divided in 2 daily infusions, administered before allogenic HPCT.
Total cumulative dose should not exceed 250 mg/metre squared (10 mg/kg).
Refractory Cytopenia
Recommended dose is 125 mg/metre squared/day (5 mg/kg/day) as a single daily infusion, administered for 3 consecutive days before allogenic HPCT.
Total cumulative dose should not exceed 375 mg/metre squared (15 mg/kg)
Genetic diseases
Recommended dose is 125 mg/metre squared/day (5 mg/kg/day) as a single daily infusion, administered for 2 consecutive days before allogenic HPCT.
Total cumulative dose should not exceed 250 mg/metre squared (10 mg/kg)
Administration
To be administered over 2 to 4 hours by intravenous infusion via a central venous catheter.
Contraindications
Breastfeeding
Pregnancy
Precautions and Warnings
Females of childbearing potential
History of progenitor cell transplantation
History of radiotherapy
Restricted sodium intake
Cardiac disorder
Hepatic impairment
Myelosuppression
Porphyria
Renal impairment
Administration of live vaccines is not recommended
Live virus vaccine should not be given for 3 months after treatment
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Consider use of anti-infective prophylaxis during neutropenic phase
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment to be prescribed under the supervision of a specialist
Accidental contact of soln with skin/mucous membranes-rinse well with water
Consult local policy on the safe use of anti-cancer drugs
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Monitor full blood count and differential WBC before and during therapy
Daily WBC & platelet counts during therapy and 30 days post transplant
Monitor cardiac function
Monitor closely patient with pre-existing hepatic impairment
Monitor levels of hepatic enzymes and bilirubin
Monitor renal function regularly
Consider G-CSF in severe neutropenia / agranulocytosis
Consider hepatic veno-occlusive disease if hepatic impairment occurs
Potentially mutagenic and carcinogenic
Risk of myelodysplastic syndrome and secondary malignancies
Advise patient not to take St John's wort concurrently
May cause impaired fertility
Female: Ensure adequate contraception during treatment
Male: Contraception required during and for 1 year after treatment
Patients who have received prior radiation therapy, greater than or equal to 3 cycles of chemotherapy, or prior progenitor cell transplant may be at an increased risk of hepatic veno-occlusive disease.
Platelet, red blood cell support and growth factors such as granulocyte-colony stimulating factor should be used as indicated.
Pregnancy and Lactation
Pregnancy
Thiotepa is contraindicated during pregnancy.
The manufacturer recommends that thiotepa is contraindicated during pregnancy.
It is not known if thiotepa crosses the placenta. However, the molecular weight is low enough that transfer should be expected.
There are no well-controlled studies in pregnant women. Thiotepa is structurally related to the nitrogen mustard compounds and has been shown to cause embryofoetal lethality and teratogenicity.
The effect of concurrent therapies must also be considered.
Lactation
Thiotepa is contraindicated during breastfeeding.
The manufacturer states that due to the potential for serious toxicity in the nursing infant it is recommended that breastfeeding is discontinued during treatment. There are no data on the excretion of thiotepa in human breast-milk. However, the low molecular weight suggests that excretion into breast milk is to be expected.
The effect of concurrent therapies must also be considered.
Side Effects
Abdominal pain
Agitation
Alopecia
Amenorrhoea
Anaemia
Anorexia
Anxiety
Arrhythmias
Arthralgia
Asthenia
Azoospermia
Back pain
Blurred vision
Cardiac failure
Cardiomyopathy
Cataracts
Cerebral haemorrhage
Cerebrovascular accident
Chills
Cognitive impairment
Colitis
Confusion
Conjunctivitis
Constipation
Convulsions
Cough
Cystitis
Decreased appetite
Delirium
Diarrhoea
Dizziness
Dyspepsia
Dysuria
Elevated amylase levels
Embolism
Encephalopathy
Enteritis
Epistaxis
Erythema
Extrapyramidal effects
Febrile neutropenia
Gastro-intestinal perforation
Gastro-intestinal ulceration
Generalised oedema
Graft versus host disease
Granulocytopenia
Haematuria
Haemorrhage
Haemorrhagic cystitis
Hallucinations
Headache
Hearing disturbances
Hepatomegaly
Hyperglycaemia
Hypersensitivity reactions
Hypertension
Hypoxia
Ileus
Impaired fertility
Increase in blood urea or creatinine
Increase in serum transaminases
Increased susceptibility to infection
Jaundice
Leukoencephalopathy
Leukopenia
Local pain (injection site)
Lymphoedema
Menopausal-like symptoms
Mental status changes
Multiorgan failure
Myalgia
Myocarditis
Nausea
Nervousness
Oesophagitis
Oliguria
Ototoxicity
Pancytopenia
Paraesthesia
Pituitary disorder
Pneumonitis
Pruritus
Pulmonary oedema
Pyrexia
Rash
Renal failure
Second primary malignancies
Sepsis
Serum bilirubin increased
Skin pigmentation changes
Stevens-Johnson syndrome
Stomatitis
Tachycardia
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Vaginal haemorrhage
Veno-occlusive disease
Vomiting
Weight gain
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: December 2015
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Summary of Product Characteristics: Tepadina 15 mg powder for concentrate for solution for infusion. Adienne S.r.l. S.U.. Revised November 2020.
Summary of Product Characteristics: Tepadina 100 mg powder for concentrate for solution for infusion. Adienne S.r.l. S.U.. Revised November 2020.
Summary of Product Characteristics: Tepadina 400 mg powder and solvent for solution for infusion. Adienne S.r.l. S.U.. Revised May 2021.
The Norwegian Porphyria Centre (NAPOS).
Available at: https://www.drugs-porphyria.org
Last revised: 3 July 2010
Last accessed: 3 August 2021
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