THIOTEPA- thiotepa injection, powder, lyophilized, for solution
Hikma
Rx ONLY
DESCRIPTION
Thiotepa for Injection, USP is an ethylenimine-type compound. It is supplied as a non-pyrogenic, sterile Iyophilized powder for intravenous, intracavitary or intravesical administration, containing 15 mg of thiotepa. Thiotepa is a synthetic product with antitumor activity. The chemical name for thiotepa is Tris(1-aziridinyl)phosphine sulfide.
Thiotepa has the molecular formula C6 H12 N3 PS, and a molecular weight of 189.22. When reconstituted with sterile water for injection, the resulting solution has a pH of approximately 5.5 to 7.5. Thiotepa is stable in alkaline medium and unstable in acid medium.
CLINICAL PHARMACOLOGY
Thiotepa is a cytotoxic agent of the polyfunctional type, related chemically and pharmacologically to nitrogen mustard. The radiomimetic action of thiotepa is believed to occur through the release of ethylenimine radicals which, like irradiation, disrupt the bonds of DNA. One of the principal bond disruptions is initiated by alkylation of guanine at the N-7 position, which severs the linkage between the purine base and the sugar and liberates alkylated guanines.
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:
Adenocarcinoma of the breast.
Adenocarcinoma of the ovary.
For controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities.
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While now largely superseded by other treatments, thiotepa has been effective against other lymphomas, such as lymphosarcoma and Hodgkin's disease.
CONTRAINDICATIONS
Thiotepa is contraindicated in patients with a known hypersensitivity (allergy) to this preparation.
Therapy is probably contraindicated in cases of existing hepatic, renal, or bone-marrow damage. However, if the need outweighs the risk in such patients, thiotepa may be used in low dosage, and accompanied by hepatic, renal and hemopoietic function tests.
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.
DOSAGE AND ADMINISTRATION
Since absorption from the gastrointestinal tract is variable, thiotepa should not be administered orally.
Dosage must be carefully individualized. A slow response to thiotepa does not necessarily indicate a lack of effect. Therefore, increasing the frequency of dosing may only increase toxicity. After maximum benefit is obtained by initial therapy, it is necessary to continue the patient on maintenance therapy (1 to 4 week intervals). In order to continue optimal effect, maintenance doses should not be administered more frequently than weekly in order to preserve correlation between dose and blood counts.
