Thiotepa
Generic: THIOTEPA
Basic Information
Manufacturer
Hikma Pharmaceuticals USA Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRACAVITARY
FDA Set ID
b19b03db-471d-4ee7-b1b8-6eccc39c41b0
Indications & Usage
INDICATIONS AND USAGE Thiotepa for Injection, USP has been tried with varying results in the palliation of a wide variety of neoplastic diseases.
However, the most consistent results have been seen in the following tumors: 1.Adenocarcinoma of the breast.
2.Adenocarcinoma of the ovary.
3.For controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities.
4.For the treatment of superficial papillary carcinoma of the urinary bladder.
While now largely superseded by other treatments, thiotepa has been effective against other lymphomas, such as lymphosarcoma and Hodgkin's disease.
However, the most consistent results have been seen in the following tumors: 1.Adenocarcinoma of the breast.
2.Adenocarcinoma of the ovary.
3.For controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities.
4.For the treatment of superficial papillary carcinoma of the urinary bladder.
While now largely superseded by other treatments, thiotepa has been effective against other lymphomas, such as lymphosarcoma and Hodgkin's disease.
Warnings
WARNINGS Death has occurred after intravesical administration, caused by bone-marrow depression from systematically absorbed drug.
Death from septicemia and hemorrhage has occurred as a direct result of hematopoietic depression by thiotepa.
Thiotepa is highly toxic to the hematopoietic system.
A rapidly falling white blood cell or platelet count indicates the necessity for discontinuing or reducing the dosage of thiotepa.
Weekly blood and platelet counts are recommended during therapy and for at least 3 weeks after therapy has been discontinued.
Thiotepa can cause fetal harm when administered to a pregnant woman.
Thiotepa given by the intraperitoneal (IP) route was teratogenic in mice at doses ≥ 1 mg/kg (3.2 mg/m 2 ), approximately 8-fold less than the maximum recommended human therapeutic dose (0.8 mg/kg, 27 mg/m 2 ), based on body-surface area.
Thiotepa given by the IP route was teratogenic in rats at doses ≥ 3 mg/kg (21 mg/m 2 ), approximately equal to the maximum recommended human therapeutic dose, based on body-surface area.
Thiotepa was lethal to rabbit fetuses at a dose of 3 mg/kg (41 mg/m 2 ), approximately two times the maximum recommended human therapeutic dose based on body-surface area.
Effective contraception should be used during thiotepa therapy if either the patient or partner is of childbearing potential.
There are no adequate and well-controlled studies in pregnant women.
If thiotepa is used during pregnancy, or if pregnancy occurs during thiotepa therapy, the patient and partner should be apprised of the potential hazard to the fetus.
Thiotepa is a polyfunctional alkylating agent, capable of cross-linking the DNA within a cell and changing its nature.
The replication of the cell is, therefore, altered, and thiotepa may be described as mutagenic.
An in vitro study has shown that it causes chromosomal aberrations of the chromatid type and that the frequency of induced aberrations increases with the age of the subject.
Like many alkylating agents, thiotepa has been reported to be carcinogenic when administered to laboratory animals.
Carcinogenicity is shown most clearly in studies using mice, but there is some evidence of carcinogenicity in man.
In patients treated with thiotepa, cases of myelodysplastic syndromes and acute non-lymphocytic leukemia have been reported.
Death from septicemia and hemorrhage has occurred as a direct result of hematopoietic depression by thiotepa.
Thiotepa is highly toxic to the hematopoietic system.
A rapidly falling white blood cell or platelet count indicates the necessity for discontinuing or reducing the dosage of thiotepa.
Weekly blood and platelet counts are recommended during therapy and for at least 3 weeks after therapy has been discontinued.
Thiotepa can cause fetal harm when administered to a pregnant woman.
Thiotepa given by the intraperitoneal (IP) route was teratogenic in mice at doses ≥ 1 mg/kg (3.2 mg/m 2 ), approximately 8-fold less than the maximum recommended human therapeutic dose (0.8 mg/kg, 27 mg/m 2 ), based on body-surface area.
Thiotepa given by the IP route was teratogenic in rats at doses ≥ 3 mg/kg (21 mg/m 2 ), approximately equal to the maximum recommended human therapeutic dose, based on body-surface area.
Thiotepa was lethal to rabbit fetuses at a dose of 3 mg/kg (41 mg/m 2 ), approximately two times the maximum recommended human therapeutic dose based on body-surface area.
Effective contraception should be used during thiotepa therapy if either the patient or partner is of childbearing potential.
There are no adequate and well-controlled studies in pregnant women.
If thiotepa is used during pregnancy, or if pregnancy occurs during thiotepa therapy, the patient and partner should be apprised of the potential hazard to the fetus.
Thiotepa is a polyfunctional alkylating agent, capable of cross-linking the DNA within a cell and changing its nature.
The replication of the cell is, therefore, altered, and thiotepa may be described as mutagenic.
An in vitro study has shown that it causes chromosomal aberrations of the chromatid type and that the frequency of induced aberrations increases with the age of the subject.
Like many alkylating agents, thiotepa has been reported to be carcinogenic when administered to laboratory animals.
Carcinogenicity is shown most clearly in studies using mice, but there is some evidence of carcinogenicity in man.
In patients treated with thiotepa, cases of myelodysplastic syndromes and acute non-lymphocytic leukemia have been reported.
Adverse Reactions
ADVERSE REACTIONS In addition to its effect on the blood-forming elements (see WARNINGS and PRECAUTIONS sections), thiotepa may cause other adverse reactions.
General Fatigue, weakness.
Febrile reaction and discharge from a subcutaneous lesion may occur as the result of breakdown of tumor tissue.
Hypersensitivity Reactions Allergic reactions - rash, urticaria, laryngeal edema, asthma, anaphylactic shock, wheezing.
Local Reactions Contact dermatitis, pain at the injection site.
Gastrointestinal Nausea, vomiting, abdominal pain, anorexia.
Renal Dysuria, urinary retention.
There have been rare reports of chemical cystitis or hemorrhagic cystitis following intravesical, but not parenteral administration of thiotepa.
Respiratory Prolonged apnea has been reported when succinylcholine was administered prior to surgery, following combined use of thiotepa and other anticancer agents.
It was theorized that this was caused by decrease of pseudocholinesterase activity caused by the anticancer drugs.
Neurologic Dizziness, headache, blurred vision.
Skin Dermatitis, alopecia.
Skin depigmentation has been reported following topical use.
Special Senses Conjunctivitis.
Reproductive Amenorrhea, interference with spermatogenesis.
General Fatigue, weakness.
Febrile reaction and discharge from a subcutaneous lesion may occur as the result of breakdown of tumor tissue.
Hypersensitivity Reactions Allergic reactions - rash, urticaria, laryngeal edema, asthma, anaphylactic shock, wheezing.
Local Reactions Contact dermatitis, pain at the injection site.
Gastrointestinal Nausea, vomiting, abdominal pain, anorexia.
Renal Dysuria, urinary retention.
There have been rare reports of chemical cystitis or hemorrhagic cystitis following intravesical, but not parenteral administration of thiotepa.
Respiratory Prolonged apnea has been reported when succinylcholine was administered prior to surgery, following combined use of thiotepa and other anticancer agents.
It was theorized that this was caused by decrease of pseudocholinesterase activity caused by the anticancer drugs.
Neurologic Dizziness, headache, blurred vision.
Skin Dermatitis, alopecia.
Skin depigmentation has been reported following topical use.
Special Senses Conjunctivitis.
Reproductive Amenorrhea, interference with spermatogenesis.