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.
AND PRECAUTIONS Cutaneous toxicity: Cleanse skin at least twice daily through 48 hours after the last dose of thiotepa for injection. ( 5.3) Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to avoid pregnancy. ( 5.8 )
5.1 Myelosuppression The consequence of treatment with high doses of thiotepa for injection together with other chemotherapy is profound myelosuppression occurring in all patients. Monitor complete blood counts, and provide supportive care for infections, anemia and thrombocytopenia until there is adequate hematopoietic recovery. For patients receiving thiotepa for injection for treatment of adenocarcinoma of the breast, adenocarcinoma of the ovary, malignant effusions and superficial papillary carcinoma of the urinary bladder, if the bone marrow has been compromised by prior irradiation or chemotherapy, or is recovering from chemotherapy, the risk of severe myelosuppression with thiotepa for injection may be increased. Perform periodic complete blood counts during the course of treatment with thiotepa for injection. Provide supportive care for infections, bleeding, and symptomatic anemia <span class="opacity-50 text-xs">[see Adverse Reactions (6.1 )]</span> . Pediatric use information is approved for Adienne SA’s TEPADINA (thiotepa) for Injection. However, due to Adienne SA’s marketing exclusivity rights, the drug product is not labeled with that information.
5.2 Hypersensitivity Clinically significant hypersensitivity reactions, including anaphylaxis, have occurred following administration of thiotepa for injection. If anaphylactic or other clinically significant allergic reaction occurs, discontinue treatment with thiotepa for injection, initiate appropriate therapy, and monitor until signs and symptoms resolve <span class="opacity-50 text-xs">[see Contraindications (4) , Adverse Reactions (6.1 )]</span> .
5.3 Cutaneous Toxicity Thiotepa for injection and/or its active metabolites may be excreted in part via skin patients receiving high-dose therapy. Treatment with thiotepa for injection may cause skin discoloration, pruritus, blistering, desquamation, and peeling that may be more severe in the groin, axillae, skin folds, in the neck area, and under dressings. Instruct patients to shower or bathe with water at least twice daily through 48 hours after administration of thiotepa for injection. Change occlusive dressing and clean the covered skin at least twice daily through 48 hours after administration of thiotepa for injection. Change bed sheets daily during treatment. Skin reactions associated with accidental exposure to thiotepa for injection may also occur. Wash the skin thoroughly with soap and water in case thiotepa solution contacts the skin. Flush mucous membranes in case of thiotepa for injection contact with mucous membranes.
5.4 Concomitant Use of Live and Attenuated Vaccines Do not administer live or attenuated viral or bacterial vaccines to a patient treated with thiotepa for injection until the immunosuppressive effects have resolved.
5.5 Hepatic Veno-Occlusive Disease Hepatic veno-occlusive disease may occur in patients who have received high-dose thiotepa for injection in conjunction with busulfan and cyclophosphamide. Monitor by physical examination, serum transaminases and bilirubin, and provide supportive care to patients who develop hepatic veno-occlusive disease. Pediatric use information is approved for Adienne SA’s TEPADINA (thiotepa) for Injection. However, due to Adienne SA’s marketing exclusivity rights, the drug product is not labeled with that information.
5.6 Central Nervous System Toxicity Fatal encephalopathy has occurred in patients treated with high doses of thiotepa. Other central nervous system toxicities, such as headache, apathy, psychomotor retardation, disorientation, confusion, amnesia, hallucinations, drowsiness, somnolence, seizures, coma, inappropriate behavior and forgetfulness have been reported to occur in a dose-dependent manner during or shortly after administration of high-dose thiotepa. Do not exceed the recommended dose of thiotepa. If severe or life-threatening central nervous system toxicity occurs, discontinue administration of thiotepa for injection and provide supportive care. Pediatric use information is approved for Adienne SA’s TEPADINA (thiotepa) for Injection. However, due to Adienne SA’s marketing exclusivity rights, the drug product is not labeled with that information.
5.7 Carcinogenicity Like many alkylating agents, thiotepa has been reported to be carcinogenic when administered to laboratory animals <span class="opacity-50 text-xs">[see Nonclinical Toxicity (13.1) ]</span> . Carcinogenicity is shown most clearly in studies using mice, but there is some evidence of carcinogenicity in man. There is an increased risk of a secondary malignancy with use of thiotepa for injection.
5.8 Embryo-Fetal Toxicity Based on the mechanism of action and findings in animals, thiotepa for injection can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of thiotepa for injection in pregnant women. 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. Advise pregnant women of the potential risk to the fetus [ see Use in Specific Populations ( 8.1 , 8.3 ) ]. Advise females of reproductive potential to use highly effective contraception during and after treatment with thiotepa for injection for at least 6 months after therapy. Advise males of reproductive potential to use effective contraception during and after treatment with thiotepa for injection for at least 1 year after therapy [ see Use in Specific Populations ( 8.1 , 8.3 ) ].
5.1 Myelosuppression The consequence of treatment with high doses of thiotepa for injection together with other chemotherapy is profound myelosuppression occurring in all patients. Monitor complete blood counts, and provide supportive care for infections, anemia and thrombocytopenia until there is adequate hematopoietic recovery. For patients receiving thiotepa for injection for treatment of adenocarcinoma of the breast, adenocarcinoma of the ovary, malignant effusions and superficial papillary carcinoma of the urinary bladder, if the bone marrow has been compromised by prior irradiation or chemotherapy, or is recovering from chemotherapy, the risk of severe myelosuppression with thiotepa for injection may be increased. Perform periodic complete blood counts during the course of treatment with thiotepa for injection. Provide supportive care for infections, bleeding, and symptomatic anemia <span class="opacity-50 text-xs">[see Adverse Reactions (6.1 )]</span> . Pediatric use information is approved for Adienne SA’s TEPADINA (thiotepa) for Injection. However, due to Adienne SA’s marketing exclusivity rights, the drug product is not labeled with that information.
5.2 Hypersensitivity Clinically significant hypersensitivity reactions, including anaphylaxis, have occurred following administration of thiotepa for injection. If anaphylactic or other clinically significant allergic reaction occurs, discontinue treatment with thiotepa for injection, initiate appropriate therapy, and monitor until signs and symptoms resolve <span class="opacity-50 text-xs">[see Contraindications (4) , Adverse Reactions (6.1 )]</span> .
5.3 Cutaneous Toxicity Thiotepa for injection and/or its active metabolites may be excreted in part via skin patients receiving high-dose therapy. Treatment with thiotepa for injection may cause skin discoloration, pruritus, blistering, desquamation, and peeling that may be more severe in the groin, axillae, skin folds, in the neck area, and under dressings. Instruct patients to shower or bathe with water at least twice daily through 48 hours after administration of thiotepa for injection. Change occlusive dressing and clean the covered skin at least twice daily through 48 hours after administration of thiotepa for injection. Change bed sheets daily during treatment. Skin reactions associated with accidental exposure to thiotepa for injection may also occur. Wash the skin thoroughly with soap and water in case thiotepa solution contacts the skin. Flush mucous membranes in case of thiotepa for injection contact with mucous membranes.
5.4 Concomitant Use of Live and Attenuated Vaccines Do not administer live or attenuated viral or bacterial vaccines to a patient treated with thiotepa for injection until the immunosuppressive effects have resolved.
5.6 Central Nervous System Toxicity Fatal encephalopathy has occurred in patients treated with high doses of thiotepa. Other central nervous system toxicities, such as headache, apathy, psychomotor retardation, disorientation, confusion, amnesia, hallucinations, drowsiness, somnolence, seizures, coma, inappropriate behavior and forgetfulness have been reported to occur in a dose-dependent manner during or shortly after administration of high-dose thiotepa. Do not exceed the recommended dose of thiotepa. If severe or life-threatening central nervous system toxicity occurs, discontinue administration of thiotepa for injection and provide supportive care. Pediatric use information is approved for Adienne SA’s TEPADINA (thiotepa) for Injection. However, due to Adienne SA’s marketing exclusivity rights, the drug product is not labeled with that information.
5.7 Carcinogenicity Like many alkylating agents, thiotepa has been reported to be carcinogenic when administered to laboratory animals <span class="opacity-50 text-xs">[see Nonclinical Toxicity (13.1) ]</span> . Carcinogenicity is shown most clearly in studies using mice, but there is some evidence of carcinogenicity in man. There is an increased risk of a secondary malignancy with use of thiotepa for injection.
5.8 Embryo-Fetal Toxicity Based on the mechanism of action and findings in animals, thiotepa for injection can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of thiotepa for injection in pregnant women. 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. Advise pregnant women of the potential risk to the fetus [ see Use in Specific Populations ( 8.1 , 8.3 ) ]. Advise females of reproductive potential to use highly effective contraception during and after treatment with thiotepa for injection for at least 6 months after therapy. Advise males of reproductive potential to use effective contraception during and after treatment with thiotepa for injection for at least 1 year after therapy [ see Use in Specific Populations ( 8.1 , 8.3 ) ].