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部份中文塞替派处方资料（仅供参考）
Thiotepa has the molecular formula C6H12N3PS, 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.
The pharmacokinetics of thiotepa in renal and hepatic dysfunction patients have not been evaluated. Possible pharmacokinetic interactions of thiotepa with any concomitantly administered medications have not been formally investigated. 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 While now largely superseded by other treatments, thiotepa has been effective against other lymphomas, such as lymphosarcoma and Hodgkin's disease. 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. 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/m2), approximately 8-fold less than the maximum recommended human therapeutic dose (0.8 mg/kg, 27 mg/m2), based on body-surface area. Thiotepa given by the IP route was teratogenic in rats at doses ≥ 3 mg/kg (21 mg/m2), 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/m2), 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. PRECAUTIONS GeneralThe serious complication of excessive thiotepa therapy, or sensitivity to the effects of thiotepa, is bone-marrow depression. If proper precautions are not observed thiotepa may cause leukopenia, thrombocytopenia, and anemia. Information for PatientsThe patient should notify the physician in the case of any sign of bleeding (epistaxis, easy bruising, change in color of urine, black stool) or infection (fever, chills) or for possible pregnancy to patient or partner. Effective contraception should be used during thiotepa therapy if either the patient or the partner is of childbearing potential. Laboratory TestsThe most reliable guide to thiotepa toxicity is the white blood cell count. If this falls to 3000 or less, the dose should be discontinued. Another good index of thiotepa toxicity is the platelet count; if this falls to 150,000, therapy should be discontinued. Red blood cell count is a less accurate indicator of thiotepa toxicity. If the drug is used in patients with hepatic or renal damage (see CONTRAINDICATIONS section), regular assessment of hepatic and renal function tests are indicated. Drug InteractionsIt is not advisable to combine, simultaneously or sequentially, cancer chemotherapeutic agents or a cancer chemotherapeutic agent and a therapeutic modality having the same mechanism of action. Therefore, thiotepa combined with other alkylating agents such as nitrogen mustard or cyclophosphamide or thiotepa combined with irradiation would serve to intensify toxicity rather than to enhance therapeutic response. If these agents must follow each other, it is important that recovery from the first agent, as indicated by white blood cell count, be complete before therapy with the second agent is instituted. Other drugs which are known to produce bone-marrow depression should be avoided. Carcinogenesis, Mutagenesis, Impairment of FertilityAlso see WARNINGS section. Carcinogenesis In mice, repeated IP administration of thiotepa (1.15 or 2.3 mg/kg three times per week for 52 or 43 weeks, respectively) produced a significant increase in the combined incidence of squamous-cell carcinomas of the skin, preputial gland, and ear canal, and combined incidence of lymphoma and lymphocytic leukemia. In other studies in mice, repeated IP administration of thiotepa (4 or 8 mg/kg three times per week for 4 weeks followed by a 20 week observation period or 1.8 mg/kg three times per week for 4 weeks followed by a 35 week observation period) resulted in an increased incidence of lung tumors. In rats, repeated IP administration of thiotepa (0.7 or 1.4 mg/kg three times per week for 52 or 34 weeks, respectively) produced significant increases in the incidence of squamous-cell carcinomas of the skin or ear canal, combined hematopoietic neoplasms, and uterine adenocarcinomas. Thiotepa given intravenously (IV) to rats (1 mg/kg once per week for 52 weeks) produced an increased incidence of malignant tumors (abdominal cavity sarcoma, lymphosarcoma myelosis, seminoma, fibrosarcoma, salivary gland hemangioendothelioma, mammary sarcoma, pheochromocytoma) and benign tumors. The lowest reported carcinogenic dose in mice (1.15 mg/kg, 3.68 mg/m2) is approximately 7-fold less than the maximum recommended human therapeutic dose based on body-surface area. The lowest reported carcinogenic dose in rats (0.7 mg/kg, 4.9 mg/m2) is approximately 6-fold less than the maximum recommended human therapeutic dose based on body-surface area. Mutagenesis Thiotepa was mutagenic in in vitro assays in Salmonella typhimurium, E coli, Chinese hamster lung and human lymphocytes. Chromosomal aberrations and sister chromatid exchanges were observed in vitro with thiotepa in bean root tips, human lymphocytes, Chinese hamster lung, and monkey lymphocytes. Mutations were observed with oral thiotepa in mouse at doses > 2.5 mg/kg (8 mg/m2). The mouse micronucleus test was positive with IP administration of > 1 mg/kg (3.2 mg/m2). Other positive in vivo chromosomal aberration or mutation assays included Drosophila melanogaster, Chinese hamster marrow, murine marrow, monkey lymphocyte, and murine germ cell. Impairment of Fertility Thiotepa impaired fertility in male mice at PO or IP doses ≥ 0.7 mg/kg (2.24 mg/m2), approximately 12-fold less than the maximum recommended human therapeutic dose based on body-surface area. Thiotepa (0.5 mg) inhibited implantation in female rats when instilled into the uterine cavity. Thiotepa interfered with spermatogenesis in mice at IP doses ≥ 0.5 mg/kg (1.6 mg/m2), approximately 17-fold less than the maximum recommended human therapeutic dose based on body-surface area. Thiotepa interfered with spermatogenesis in hamsters at an IP dose of 1 mg/kg (4.1 mg/m2), approximately 7-fold less than the maximum recommended human therapeutic dose based on body-surface area. Pregnancy Teratogenic Effects- Category D See WARNINGS section. Thiotepa can cause fetal harm when administered to a pregnant woman. Thiotepa given by the IP route was teratogenic in mice at doses ≥ 1 mg/kg (3.2 mg/m2), approximately 8-fold less than the maximum recommended human therapeutic dose based on body-surface area. Thiotepa given by the IP route was teratogenic in rats at doses ≥3 mg/kg (21 mg/m2), 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/m2), approximately 2 times the maximum recommended human therapeutic dose based on body-surface area. Patients of childbearing potential should be advised to avoid pregnancy. 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. Nursing MothersIt is not known whether thiotepa is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for thiotepa in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric UseSafety and effectiveness in pediatric patients have not been established. Geriatric UseClinical studies of thiotepa did not include sufficient numbers of subjects aged 65 and over to determine whether elderly subjects respond differently from younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreasing hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. ADVERSE REACTIONS In addition to its effect on the blood-forming elements (see WARNINGS and PRECAUTIONS sections), thiotepa may cause other adverse reactions. GeneralFatigue, weakness. Febrile reaction and discharge from a subcutaneous lesion may occur as the result of breakdown of tumor tissue. Hypersensitivity ReactionsAllergic reactions - rash, urticaria, laryngeal edema, asthma, anaphylactic shock, wheezing. Local ReactionsContact dermatitis, pain at the injection site. GastrointestinalNausea, vomiting, abdominal pain, anorexia. RenalDysuria, urinary retention. There have been rare reports of chemical cystitis or hemorrhagic cystitis following intravesical, but not parenteral administration of thiotepa. RespiratoryProlonged 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. NeurologicDizziness, headache, blurred vision. SkinDermatitis, alopecia. Skin depigmentation has been reported following topical use. Special SensesConjunctivitis. ReproductiveAmenorrhea, interference with spermatogenesis. OVERDOSAGE Hematopoietic toxicity can occur following overdose, manifested by a decrease in the white cell count and/or platelets. Red blood cell count is a less accurate indicator of thiotepa toxicity. Bleeding manifestations may develop. The patient may become more vulnerable to infection, and less able to combat suchinfection. Dosages within and minimally above the recommended therapeutic doses have been associated with potentially life-threatening hematopoietic toxicity. Thiotepa has a toxic effect on the hematopoietic system that is dose related. Thiotepa is dialyzable. There is no known antidote for overdosage with thiotepa. Transfusions of whole blood or platelets have proven beneficial to the patient in combating hematopoietic toxicity. 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. Preparation and Administration PrecautionsThiotepa is a cytotoxic anticancer drug and as with other potentially toxic compounds, caution should be exercised in handling and preparation of thiotepa. Skin reactions associated with accidental exposure to thiotepa may occur. The use of gloves is recommended. If thiotepa solution contacts the skin, immediately wash the skin thoroughly with soap and water. If thiotepa contacts mucous membranes, the membranes should be flushed thoroughly with water. Preparation of SolutionThiotepa for injection should be reconstituted with 1.5 mL of sterile water for injection resulting in a drug concentration of approximately 10 mg/mL. The actual withdrawable quantities and concentration achieved are illustrated in the following table:
When reconstituted with sterile water for injection, solutions of thiotepa should be stored in a refrigerator and used within 8 hours. Reconstituted solutions further diluted with sodium chloride injection should be used immediately. In order to eliminate haze, filter solutions through a 0.22 micron filter* prior to administration. Filtering does not alter solution potency. Reconstituted solutions should be clear. Solutions that remain opaque or precipitate after filtration should not be used. Polysulfone membrane (Gelman’s Sterile Aerodisc®, Single Use) or triton-free mixed ester of cellulose/PVC (Millipore’s MILLEX®-GS Filter Unit). Initial and Maintenance DosesInitially the higher dose in the given range is commonly administered. The maintenance dose should be adjusted weekly on the basis of pretreatment control blood counts and subsequent blood counts. Intravenous AdministrationThiotepa may be given by rapid intravenous administration in doses of 0.3 to 0.4 mg/kg. Doses should be given at 1 to 4 week intervals. Intracavitary AdministrationThe dosage recommended is 0.6 to 0.8 mg/kg. Administration is usually effected through the same tubing which is used to remove the fluid from the cavity involved. Intravesical AdministrationPatients with papillary carcinoma of the bladder are dehydrated for 8 to 12 hours prior to treatment. Then 60 mg of thiotepa in 30 to 60 mL of Sodium Chloride Injection is instilled into the bladder by catheter. For maximum effect, the solution should be retained for 2 hours. If the patient finds it impossible to retain 60 mL for 2 hours, the dose may be given in a volume of 30 mL. If desired, the patient may be positioned every 15 minutes for maximum area contact. The usual course of treatment is once a week for 4 weeks. The course may be repeated if necessary, but second and third courses must be given with caution since bone-marrow depression may be increased. Deaths have occurred after intravesical administration, caused by bone-marrow depression from systemically absorbed drug. Handling and DisposalFollow safe cytotoxic agent handling procedures. Several guidelines on this subject have been published.1-7 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. HOW SUPPLIED Thiotepa for Injection, USP, for single use only, is available in vials containing 15 mg of nonpyrogenic, sterile lyophilized powder, supplied as follows: NDC 0143-9565-01. Unit carton contains 1 x 15 mg single dose vial thiotepa. Store in a refrigerator between 2° to 8°C (36° to 46°F). PROTECT FROM LIGHT AT ALL TIMES. To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceutical Corp. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. For Product Inquiry call 1-877-845-0689. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b19b03db-471d-4ee7-b1b8-6eccc39c41b0 ------------------------------------------------------------ 产地国家：美国 原产地英文商品名: THIOTEPA INJ 15MG/2ML/VIAL 1VIAL/box 原产地英文药品名: THIOTEPA 中文参考商品译名: 塞替派 15毫克/2毫升/瓶 1瓶/盒 中文参考药品译名: 塞替派 生产厂家英文名: WEST WARD PHARMACEUTICAL NDC: 00143-9565-01 ------------------------------------------------------------ 产地国家：美国 原产地英文商品名: THIOTEPA 15MG SDV LYO PWD 1/EA 原产地英文药品名: THIOTEPA 中文参考商品译名: 塞替派SDV 15毫克/瓶 中文参考药品译名: 塞替派 生产厂家英文名: WEST WARD PHARMACEUTICALS NDC: 00143-9565-01 ------------------------------------------------------------ 产地国家：美国 原产地英文商品名: THIOTEPA SDV 15MG/2ML/VIAL 原产地英文药品名: THIOTEPA 中文参考商品译名: 塞替派SDV 15毫克/2毫升/瓶 中文参考药品译名: 塞替派 生产厂家中文参考译名: BEDFORD 生产厂家英文名: BEDFORD | |||||||||||||||||||||||||||||||||||||||||||||
