Thiotepa


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : IV Breast cancer; Ovarian carcinoma Dosage must be individualised. Usual range: 0.3-0.4 mg/kg 1-4 wkly. Ophth Reduction of recurrence following surgical removal of pterygium As 0.05% soln in sterile Ringer's solution: Instill every 3 hrly, for up to 6 wk. Intravesical Bladder cancer Instill ≤60 mg into the bladder of patient previously dehydrated for 8-12 hr and retained for 2 hr. May repeat wkly, for up to 4 wk. Intracavitary Malignant effusions Up to 60 mg in 20-60 mL of sterile water may be instilled after aspiration. Urethral Condylomata acuminata Instill 60 mg/wk into urethra.
Dosage Details
Intracavitary
Malignant effusions
Adult: Up to 60 mg in 20-60 mL of sterile water may be instilled after aspiration.
Elderly: Initiate at lower dose.

Intravenous
Breast cancer, Ovarian carcinoma
Adult: Dosage must be individualised. Usual range: 0.3-0.4 mg/kg via rapid IV admin every 1-4 wk. Avoid admin if WBC or platelet counts fall below acceptable levels. Stop treatment if WBC falls rapidly.
Elderly: Initiate at lower dose.

Intravesical
Bladder cancer
Adult: Up to 60 mg instilled in 30-60 mL of sterile water or sodium chloride 0.9% into the bladder of patient previously dehydrated for 8-12 hr and retained for 2 hr. Reposition patient every 15 minutes for max area contact. May be repeated once a wk for up to 4 wk. For prophylaxis of recurrence after surgical removal of bladder cancer: Up to 60 mg may be instilled at intervals of 1-2 wk, for up to 8 instillations.
Elderly: Initiate at lower dose.

Ophthalmic
Reduction of recurrence following surgical removal of pterygium
Adult: As 0.05% eye drops in sterile Ringer's solution: Instill every 3 hr for up to 6 wk after surgical removal of pterygium to reduce the possibility of recurrence.

Urethral
Condyloma acuminata
Adult: Instill 60 mg wkly into urethra.
Elderly: Initiate at lower dose.
Renal Impairment
Dose adjustment may be needed.
Hepatic Impairment
Dose adjustment may be needed.
Reconstitution
Reconstituted by adding 1.5 ml of sterile water for injection to a vial containing 15 mg of the drug or 3 ml of sterile water for injection to a vial containing 30 mg of the drug. This produces a solution with 10 mg of thiotepa per mL which should be filtered with a pore size of 0.22 micron. Reconstituted solution is hypotonic and should be further diluted with 0. 9% sodium chloride before use. If larger volumes of solution are needed for intracavitary, IV infusion, or perfusion therapy, the reconstituted solution may be diluted with sodium chloride, dextrose, dextrose and sodium chloride, Ringer's or lactated Ringer's injection. For local admin, thiotepa may be mixed with 2% procaine hydrochloride inj and/or 0.1% (1:1000) epinephrine hydrochloride inj.
Incompatibility
Y-site incompatibility: Minocycline, vinorelbine, cisplatin and filgrastim. Admixture incompatibility: Cisplatin.
Contraindications
Pregnancy; lactation; hypersensitivity; severe myelosuppression with leukocyte count <3000 cells/mm3 or platelet count <150,000 cells/mm3.
Special Precautions
Elderly; child; preexisting renal, hepatic and bone marrow function impairment. Monitor for fever, chills, sore throat, discoloration of urine, black stools or unusual bleeding or easy bruising. Monitor blood counts before initiation, at least wkly during and at least 3 wk after discontinuation of therapy; monitor hepatic and renal function.
Adverse Reactions
GI disturbances; fatigue, weakness, headache and dizziness; hypersensitivity reactions; blurred vision and conjunctivitis; amenorrhoea, impaired fertility; local irritation, frank chemical or haemorrhagic cystitis; depigmentation of periorbital skin (eye drops).
Potentially Fatal: Bone marrow depression, mutagenesis, teratogenesis and carcinogenesis.
Intracavitary/Intravesical/IT/IV/Parenteral: D
Overdosage
Overdosage symptoms are mainly extensions of common adverse reactions, especially leukopenia and thrombocytopenia, anaemia. No known antidote but whole blood or platelet transfusions have been beneficial in patients with haematopoietic toxicity. Thiotepa is removed by dialysis.
Drug Interactions
Concomitant use of other alkylating agents or irradiation enhance effect. Prolongs action of succinylcholine and other neuromuscular-blocking agents due to inhibition of plasma pseudocholinesterase. Increased risk of myelosuppression when used with colony-stimulating factors (such as filgrastim, lenograstim) 24 hr before to 24 hr after admin of cytotoxic chemotherapy. Coadmin with cyclophosphamide inhibit the metabolism of cyclophosphamide to its active metabolite and decrease both its efficacy and toxicity.
Food Interaction
Black cohosh, dong quai in oestrogen-dependent tumors.
Action
Description: Thiotepa is an ethyleneimine alkylating agent which interferes with DNA replication and transcription of RNA, resulting in the disruption of nucleic acid function. It is also immunosupressive. It may control malignant effusion by a direct antineoplastic effect after intracavitary admin. Low pH enhances reactivity of thiotepa. It has generally been replaced by cyclophosphamide and other drugs.
Pharmacokinetics:
Absorption: GI: incomplete and unreliable. IM: variable. Through serous membranes eg. the bladder and pleura: absorption to some extent.
Metabolism: Extenive metabolised to active and inactive metabolites.
Excretion: Excreted in urine as unchanged drug and metabolites.
Storage
Intracavitary:
Unconstituted powder: Store at 2-8°C; reconstituted (with sterile water for injection): store in a fridge and use within 8 hr; reconstituted solutions further diluted with sodium chloride Injection: used immediately. Protect from light.
Intravenous:
Unconstituted powder: Store at 2-8°C; reconstituted (with sterile water for injection): store in a fridge and use within 8 hr; reconstituted solutions further diluted with sodium chloride Injection: used immediately. Protect from light.
Intravesical:
Unconstituted powder: Store at 2-8°C; reconstituted (with sterile water for injection): store in a fridge and use within 8 hr; reconstituted solutions further diluted with sodium chloride Injection: used immediately. Protect from light.
Ophthalmic:
Unconstituted powder: Store at 2-8°C.
Urethral:
Unconstituted powder: Store at 2-8°C; reconstituted (with sterile water for injection): store in a fridge and use within 8 hr; reconstituted solutions further diluted with sodium chloride Injection: used immediately. Protect from light.
Disclaimer: This information is independently developed by MIMS based on Thiotepa from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
  • Thio-Tepa
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