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THIOTEPA FOR is a brand name for Thiotepa, supplied as a powder for solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Thiotepa for Injection USP (thiotepa for injection) is indicated: • in combination with other chemotherapeutic products as part of a high-dose chemotherapy (HDCT) consolidation regimen followed by autologous stem cell transplantation (ASCT) for adult patients with central nervous system (CNS) lymphoma and has been…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations Thiotepa for Injection USP should be administered under the supervision of a physician who is experienced in the use of high-dose chemotherapy (HDCT) regimens followed by stem cell transplantation (SCT). Dosing of obese patients based on total body weight may result in higher than expected thioTEPA/TEPA exposure.
Consideration might be given to using adjusted body weight for calculating body surface area. Obese patients should be closely monitored for signs of toxicity. 2 Recommended Dose and Dosage Adjustment The recommended dose for Thiotepa for Injection USP as part of HDCT regimens ranges from 185 mg/m2/day to 370 mg/m2/day, administered intravenously as one or two daily infusions over 2 to 3 consecutive days prior to ASCT.
Do not exceed a total maximum cumulative dose of 750 mg/m2 during the administration of the HDCT regimen. Table 1 - Thiotepa for injection high-dose chemotherapy regimens used in CNS lymphoma patients Reference Days of thiotepa for injection administrationa HDCT regimen Thiotepa for injection Dose Total Daily Dose Cumulative Dose Cheng 2003 Days -8 to -7 TT/Bu/Cy 300 mg/m2 600 mg/m2 Sierra del Rio 2011 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Illerhaus 2008 Days -5 to -4 TT/BCNU 185 mg/m2 370 mg/m2 Alimohamed 2012 Days -8 and -7 TT/Bu/Cy 300 mg/m2 600 mg/m2 Illerhaus 2006 Days -5 to -4 TT/BCNU 185 mg/m2 370 mg/m2 Montemurro 2007 Days -4 to-3 TT/Bu 185 mg/m2 370 mg/m2 Omuro 2015 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Bojic 2015 Days -5 to -4 TT/BCNU/Rb 185 mg/m2 370 mg/m2 Soussain 1996 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Soussain 2001 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Soussain 2008 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Soussain 2012 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Cote 2012 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Chen 2015 Days -9 to -7 TT/Bu/Cy/R 250 mg/m2 750 mg/m2 Lee 2015 Days -4 to -3 TT/Bu 185 mg/m2 370 mg/m2 Oh 2016 Days -8 to -7 TT/Bu/Cy 300 mg/m2 600 mg/m2 Days -6 to -5 TT/Bu/Mel/R 250 mg/m2 500 mg/m2 Korfel 2013 Days -4 to -3 TT/BCNU/VP16 370 mg/m2 740 mg/m2 Welch 2015 Days -9 to -7 TT/Bu/Cy 250mg/m2 750 mg/m2 aInfusion of autologous blood stem cells on Day 0; bThree patients additionally received rituximab; TT: thiotepa for injection; Bu: Busulfan; Cy: Cyclophosphamide: BCNU: Carmustine; VP-16: Etoposide; R: Rituximab; Mel: Melphalan The recommended doses of Thiotepa for Injection USP are intended only as part of a HDCT regimen followed by SCT.
1 Adverse Reaction Overview The most commonly reported adverse events in the clinical studies of CNS lymphoma patients treated with thiotepa for injection-containing high-dose chemotherapy (HDCT) were myelosupression, infections, diarrhea, nausea, vomiting, stomatitis, edema, mucositis, neurotoxicity, skin rash and alopecia.
Serious adverse events included thrombocytopenia, neutropenia, pancytopenia, febrile neutropenia, refractory thrombocytopenia, hemorrhage, pulmonary embolism, pneumonia, sepsis, leukoencephalopathy, micro-angiopathy, convulsion, extrapyramidal symptoms, delirium, mucositis, veno-occlusive disease, gastrointestinal graft-versus-host disease, typhilitis, pancreatitis, hemorrhagic cystitis, acute renal insufficiency and Stevens-Johnson syndrome.
2 Clinical Trial Adverse Reactions Treatment emergent adverse events reported with the use of high-dose thiotepa for injection as part of a high-dose chemotherapy (HDCT) regimen followed by autologous stem cell transplantation (ASCT) are derived from published literature where CNS lymphoma patients were treated.
As such, the safety information is limited by the information selected for inclusion into published reports. Adverse events in the tables below are not pooled nor listed by MedDRA organ classes as there are major reporting differences across publications.
R. R. R. R. R. Thiotepa for Injection USP Page 18 of 46 Reference Na Adverse Events Grade 1-2 or moderate (n) Adverse Events Grade 3-4 or serious (n) Adverse Events Grade 5 (n) Soussain, 2001 20 Infection (15) Neutropenia (20) Thrombocytopenia (20) Infection (4) Veno-occlusive disease (1) Encephalopathy (2) Leukoencephalopathy (3) Hemorrhage (1) Leukoencephalopathy (2) Soussain, 2008 27 Leukoencephalopathy (2) Leukoencephalopathy (3) Neurotoxicity (1) Soussain, 2012 32b Pancreatitis (1) Acute renal insufficiency (1) Hemorrhagic cystitis (1) Acute respiratory distress syndrome (1) Multi-organ failure (1) Pulmonary embolism (1) Sepsis (2) Neurotoxicity (4) a: Number of enrolled patients that were treated with a thiotepa for injection -containing HDCT regimen.
). • Concomitant use with live virus or bacterial vaccines including yellow fever vaccine (see 7 WARNINGS AND PRECAUTIONS). Thiotepa for Injection USP Page 6 of 46 3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions Thiotepa for Injection USP should only be administered under the supervision of a physician who is experienced in the use of high-dose chemotherapy (HDCT) and stem cell transplantation (SCT).
• Profound myelosuppression (anemia, neutropenia and thrombocytopenia) including refractory and fatal cases (see 7 WARNINGS AND PRECAUTIONS, Hematologic). • Cardiotoxicity may occur. Cardiac function must be monitored regularly and caution is advised in patients with history of cardiac disease (see 7 WARNINGS AND PRECAUTIONS, Cardiovascular).
• Hepatotoxicity: Liver function must be monitored regularly and caution is advised in patients with hepatic impairment (see 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic and Patients with Hepatic Impairment). • Patients who have received prior radiation therapy, greater than or equal to three cycles of chemotherapy, or prior SCT may be at an increased risk of hepatic veno- occlusive disease (see 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic, Patients with Hepatic Impairment, Patients with Renal Impairment and Special Populations).
• Pulmonary toxicity, including fatal cases, may occur and there may be additive effects produced by other cytotoxic agents (busulfan, fludarabine and cyclophosphamide) (see 7 WARNINGS AND PRECAUTIONS, Respiratory and 9 DRUG INTERACTIONS).
• Neurotoxicity may be greater in patients with prior brain or craniospinal irradiation (see 7 WARNINGS AND PRECAUTIONS, Neurologic). • Renal toxicity (see 7 WARNINGS AND PRECAUTIONS, Renal). • Thiotepa for Injection USP could cause fetal harm when administered to a pregnant female (see 7 WARNINGS AND PRECAUTIONS, Special Populations, Pregnant Women).
Thiotepa for Injection USP is contraindicated in: • Patients who are hypersensitive to this drug or component of the container. For a complete listing, see the 6 DOSAGE FORMS, STRENGHTS, COMPOSITION AND PACKAGING section of the product monograph.
• Female patients who are pregnant or breastfeeding (see 7 WARNINGS AND PRECAUTIONS). • Concomitant use with live virus or bacterial vaccines including yellow fever vaccine (see 7 WARNINGS AND PRECAUTIONS). Thiotepa for Injection USP Page 6 of 46
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Thiotepa for Injection USP Page 8 of 46 Special populations: • Renal impairment:
The safety and efficacy of high-dose thiotepa for injection has not been established in patients with renal impairment. Dedicated pharmacokinetic studies in patients with renal impairment have not been conducted. Patients with renal impairment should be treated with caution and monitored for signs of toxicity.
• Hepatic impairment: The safety and efficacy of high-dose thiotepa for injection has not been established in patients with hepatic impairment. Thiotepa for Injection is mainly metabolized by the liver and the risk of increased exposure in patients with hepatic impairment is unknown.
Patients with hepatic impairment should be treated with caution and monitored for signs of toxicity. 3 Pharmacokinetics, Special Populations and Conditions). • Geriatrics (>65 years of age): There is limited clinical data on the use of high-dose thiotepa for injection as part of a HDCT regimen in geriatric patients with CNS lymphoma.
Caution is needed in these patients. • Pediatrics (<18 years of age): Health Canada has not authorized an indication for pediatric use. 5 mL 10 mg/mL 100 mg 10 mL 10 mL 10 mg/mL Thiotepa for Injection USP must be reconstituted with sterile water for injection.
Using a syringe fitted with a needle, aseptically withdraw sterile water for injection (see chart above). Inject the content of the syringe into the vial through the rubber stopper. Remove the syringe and the needle and mix manually by repeated inversions.
Only clear colourless solutions, without any particulate matter, must be used. Reconstituted solutions may occasionally show opalescence; such solutions can still be administered. Thiotepa for Injection USP Page 9 of 46 For management of a suspected drug overdose contact your regional poison control centre.
5 and 1 mg/mL. 9%) solution for injection. 2 μm in-line filter (polyethersulfone-fluid filter membrane B. Braun). This medicinal product must not be mixed with other medicinal products except those mentioned in Reconstitution. 4 Administration As with all parenteral drug products, intravenous admixtures should be inspected visually for clarity, particulate matter, precipitate, discoloration and leakage prior to administration.
Thiotepa for Injection USP must be administered by a qualified healthcare professional as a 2 to 4 hours intravenous infusion via a central venous catheter. 2 […]
b: Retrospective studies over 79 patients, of which 47 were from Soussain 2001 and Soussain 2008. Here presented data relate to the remaining 32 patients only. R. R. : not reported Table 7 - Treatment emergent adverse events reported in newly diagnosed or relapsed PCNSL patients administered with a thiotepa for injection-containing HDCT regimen Reference Na Adverse Events Grade 1-2 or moderate (n) Adverse Events Grade 3-4 or serious (n) Adverse Events Grade 5 (n) Thiotepa for Injection USP Page 19 of 46 Reference Na Adverse Events Grade 1-2 or moderate (n) Adverse Events Grade 3-4 or serious (n) Adverse Events Grade 5 (n) Cheng, 2003 7* Mucositis (7) Herpes zoster (1) Febrile neutropenia (6) Hemorrhagic cystitis (1) Diarrhea (1) Cholestasis (1) Septic shock (1) a: Number of enrolled patients that were treated with a thiotepa for injection -containing HDCT regimen.
R. R. Chen, 2015 29c Mucositis (common) Diarrhea (common) Neutropenia (29) Thrombocytopenia (29) Bacterial infection (9) Fungal […]
• Serious drug interactions (see 9 DRUG INTERACTIONS). 1 Dosing Considerations Thiotepa for Injection USP should be administered under the supervision of a physician who is experienced in the use of high-dose chemotherapy (HDCT) regimens followed by stem cell transplantation (SCT).
Dosing of obese patients based on total body weight may result in higher than expected thioTEPA/TEPA exposure. Consideration might be given to using adjusted body weight for calculating body surface area. Obese patients should be closely monitored for signs of toxicity.
2 Recommended Dose and Dosage Adjustment The recommended dose for Thiotepa for Injection USP as part of HDCT regimens ranges from 185 mg/m2/day to 370 mg/m2/day, administered intravenously as one or two daily infusions over 2 to 3 consecutive days prior to ASCT.
Do not exceed a total maximum cumulative dose of 750 mg/m2 during the administration of the HDCT regimen. Table 1 - Thiotepa for injection high-dose chemotherapy regimens used in CNS lymphoma patients Reference Days of thiotepa for injection administrationa HDCT regimen Thiotepa for injection Dose Total Daily Dose Cumulative Dose Cheng 2003 Days -8 to -7 TT/Bu/Cy 300 mg/m2 600 mg/m2 Sierra del Rio 2011 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Illerhaus 2008 Days -5 to -4 TT/BCNU 185 mg/m2 370 mg/m2 Alimohamed 2012 Days -8 and -7 TT/Bu/Cy 300 mg/m2 600 mg/m2 Illerhaus 2006 Days -5 to -4 TT/BCNU 185 mg/m2 370 mg/m2 Montemurro 2007 Days -4 to-3 TT/Bu 185 mg/m2 370 mg/m2 Omuro 2015 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Bojic 2015 Days -5 to -4 TT/BCNU/Rb 185 mg/m2 370 mg/m2 Soussain 1996 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Soussain 2001 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Soussain 2008 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Soussain 2012 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Cote 2012 Days -9 to -7 TT/Bu/Cy 250 mg/m2 750 mg/m2 Chen 2015 Days -9 to -7 TT/Bu/Cy/R 250 mg/m2 750 mg/m2 Lee 2015 Days -4 to -3 TT/Bu 185 mg/m2 370 mg/m2 Oh 2016 Days -8 to -7 TT/Bu/Cy 300 mg/m2 600 mg/m2 Days -6 to -5 TT/Bu/Mel/R 250 mg/m2 500 mg/m2 Korfel 2013 Days -4 to -3 TT/BCNU/VP16 370 mg/m2 740 mg/m2 Welch 2015 Days -9 to -7 TT/Bu/Cy 250mg/m2 750 mg/m2 aInfusion of autologous blood stem cells on Day 0; bThree patients additionally received rituximab; TT: thiotepa for injection; Bu: Busulfan; Cy: Cyclophosphamide: BCNU: Carmustine; VP-16: Etoposide; R: Rituximab; Mel: Melphalan The recommended doses of Thiotepa for Injection USP are intended only as part of a HDCT regimen followed by SCT.
Thiotepa for Injection USP Page 8 of 46 Special populations: • Renal impairment:
The safety and efficacy of high-dose thiotepa for injection has not been established in patients with renal impairment. Dedicated pharmacokinetic studies in patients with renal impairment have not been conducted. Patients with renal impairment should be treated with caution and monitored for signs of toxicity.
• Hepatic impairment: The safety and efficacy of high-dose thiotepa for injection has not been established in patients with hepatic impairment. Thiotepa for Injection is mainly metabolized by the liver and the risk of increased exposure in patients with hepatic impairment is unknown.
Patients with hepatic impairment should be treated with caution and monitored for signs of toxicity. 3 Pharmacokinetics, Special Populations and Conditions). • Geriatrics (>65 years of age): There is limited clinical data on the use of high-dose thiotepa for injection as part of a HDCT regimen in geriatric patients with CNS lymphoma.
Caution is needed in these patients. • Pediatrics (<18 years of age): Health Canada has not authorized an indication for pediatric use. 3 Reconstitution Parenteral Products: Reconstitution of vials Reconstitute with Sterile Water for Injection as follows: Table 2 - Reconstitution Vial Size Volume of Sterile Water to be Added to Vial Approximate […]