Version May 2024
Myelosuppression: Thiotepa may cause severe marrow suppression, and high doses may cause marrow ablation with resulting infection or bleeding. Monitor hematologic laboratory parameters. Hematopoietic progenitor (stem) cell transplantation is required to prevent potentially fatal complications of the prolonged myelosuppression after high doses of thiotepa.
Carcinogenicity: Thiotepa should be considered potentially carcinogenic in humans.
Note: Antiemetics are recommended to prevent nausea and vomiting; thiotepa (IV) is associated with a moderate emetic potential (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]). Although included in the manufacturer's labeling as approved uses, other contemporary therapies have replaced the use of thiotepa for the treatment of papillary bladder, ovarian, and breast cancers, as well as malignant intracavitary effusions.
Hematopoietic cell transplant conditioning regimen for CNS malignancy (off-label use): IV: 250 mg/m2/day for 3 days beginning 9 days prior to transplant (in combination with busulfan and cyclophosphamide) (Soussain 2008; DeFilipp 2017) or 150 mg/m2/dose every 12 hours for 6 doses, followed by cell reinfusion 96 hours after completion of thiotepa (Abrey 2006).
Leptomeningeal metastases (off-label use/route): Intrathecal: 10 mg twice a week (on days 1 and 4 each week) for 8 weeks (Grossman 1993).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; decreased renal excretion may result in increased thiotepa and TEPA plasma concentrations and increased toxicity. Monitor patients with moderate (CrCl 30 to 59 mL/minute) to severe (CrCl <30 mL/minute) impairment for toxicity.
Hemodialysis: Thiotepa is dialyzable.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; thiotepa is extensively hepatically metabolized. Moderate (bilirubin >1.5 to 3 times ULN and any AST) or severe (bilirubin >3 times ULN and any AST) impairment may result in increased plasma concentrations and increased toxicity. Monitor closely for toxicity.
American Society for Blood and Marrow Transplantation (ASBMT) practice guideline committee position statement on chemotherapy dosing in obesity: Utilize actual body weight (full weight) for calculation of body surface area in thiotepa dosing for hematopoietic cell transplant conditioning regimens in adult patients weighing ≤120% of their ideal body weight (IBW). In patients weighing >120% IBW, utilize adjusted body weight 40% (ABW40) to calculate BSA (ASBMT [Bubalo 2014]).
ABW40: Adjusted wt (kg) = Ideal body weight (kg) + 0.4 [actual wt (kg) - ideal body weight (kg)]
Central nervous system toxicity, severe or life-threatening: Discontinue thiotepa and manage as clinically indicated, including supportive care.
Hypersensitivity reactions (eg, anaphylaxis or other clinically significant reaction): Discontinue thiotepa and manage as appropriate; monitor until signs/symptoms resolve.
Refer to adult dosing.
(For additional information see "Thiotepa: Pediatric drug information")
Note: Dosing and frequency may vary by protocol; refer to individual protocols. In pediatric patients, dosing may be based on either BSA (mg/m2) or weight (mg/kg); use extra precaution to verify dosing parameters during dosage calculations.
Antiemetics may be recommended for prevention of nausea and vomiting. In pediatric patients, doses ≥300 mg/m2 are associated with a high emetic potential and doses <300 mg/m2 are associated with a low emetic potential (POGO [Dupuis 2011]; POGO [Paw Cho Sing 2019]).
CNS malignancy, newly diagnosed, high-dose chemotherapy followed by autologous stem cell rescue (ASCR), consolidation: Infants ≥6 months and Children <3 years: IV: 10 mg/kg/dose daily for 2 days on days 0 and 1 in combination with carboplatin, followed by ASCR (Cohen 2015).
CNS malignancy, recurrent or refractory followed by autologous stem cell rescue (ASCR):
Infants and Children ≤25 kg: IV: 6.67 mg/kg/dose daily for 3 days followed by ASCR approximately 72 hours after the third dose. A second cycle of thiotepa/ASCR was administered at least 28 days after completion of first course if sufficient hematologic recovery and no tumor progression (Osorio 2018).
Children and Adolescents >25 kg: IV: 200 mg/m2/dose daily for 3 days followed by ASCR approximately 72 hours after the third dose. A second cycle of thiotepa/ASCR was administered at least 28 days after completion of first course if sufficient hematologic recovery and no tumor progression (Osorio 2018).
Hematopoietic stem cell transplant (HSCT), autologous, conditioning regimen: Infants, Children, and Adolescents: IV: 300 mg/m2/dose daily for 3 days beginning 8 days prior to transplant OR 300 mg/m2/dose daily for 3 days beginning 5 days prior to transplant in combination with other preconditioning therapies (protocols vary). For infants, some protocols report using a dose of 10 mg/kg/dose daily for 3 days (Chi 2004; Dunkel 2010; Fangusaro 2008; Finlay 2008; Gilheeney 2010; Grodman 2009; Guidi 2020; Kushner 2001).
Hematopoietic stem cell transplant (HSCT) for acute leukemias; allogeneic, conditioning regimens:
Treosulfan/fludarabine/thiotepa regimen: Infants, Children, and Adolescents: IV: 5 mg/kg/dose daily for 2 days starting on day −2 in combination with treosulfan and fludarabine (Kalwak 2020).
TBI-Thio-Cy regimen: Children and Adolescents: IV: 5 mg/kg/dose for 2 doses over 1 or 2 days beginning either 7 or 4 days prior to transplant depending on protocol in combination with total body irradiation and cyclophosphamide (Bunin 2005; Zecca 1999).
Clo-Mel-Thio: Children and Adolescents: IV: 10 mg/kg/dose daily for 1 day beginning 4 days prior to transplant in combination with clofarabine and melphalan; patients were receiving second or third HSCT (Spitzer 2016).
Hematopoietic stem cell transplant (HSCT) for beta-thalassemia, class 3; allogeneic conditioning: Infants, Children, and Adolescents: Tepadina: IV: 5 mg/kg/dose every 12 hours for 2 doses 6 days prior to HSCT in combination with high-dose busulfan and cyclophosphamide (manufacturer's labeling).
Hematopoietic stem cell transplant (HSCT) for neuroblastoma; autologous, conditioning regimen:
Single transplant: Children and Adolescents: IV: 300 mg/m2/dose daily for 3 days for a total dose of 900 mg/m2 beginning 8 days prior to transplant (day −8, −7, −6) in combination with carboplatin and topotecan (Kushner 2006).
Tandem transplant:
Infants and Children ≤12 kg: IV: 10 mg/kg/dose daily for 3 days beginning 7 days before the first transplant and followed by cyclophosphamide (Park 2019).
Children >12 kg and Adolescents: IV: 300 mg/m2/dose daily for 3 days beginning 7 days before the first transplant and followed by cyclophosphamide (Park 2019).
Hematopoietic stem cell transplant (HSCT) for nonmalignant hematologic disorders, allogeneic, conditioning regimens: Infants, Children, and Adolescents: IV: 10 mg/kg/dose as a single dose in a fludarabine-based combination regimen (Mussetti 2016).
Leukemia, relapsed or refractory:
TVTC regimen:
Infants: IV: 0.5 mg/kg/dose over 4 hours on day 2 of a 28-day regimen in combination with topotecan, clofarabine, and vinorelbine; in the trial, the youngest patient was 8 months of age (Steinherz 2010).
Children and Adolescents: IV: 15 mg/m2/dose over 4 hours on day 2 of a 28-day regimen in combination with topotecan, clofarabine, vinorelbine (Shukla 2014; Steinherz 2010).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients. Refer to specific protocol for management in pediatric patients if available.
Adult:
Central nervous system toxicity, severe or life-threatening: Discontinue thiotepa and provide supportive care.
Hypersensitivity reactions (eg, anaphylaxis or other clinically significant reaction): Discontinue thiotepa and manage as appropriate; monitor until signs/symptoms resolve.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; reduced dose may be warranted. Use may be contraindicated with existing renal impairment and should be limited to cases where benefit outweighs risk.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; reduced dose may be warranted. Use may be contraindicated with existing hepatic impairment and should be limited to cases where benefit outweighs risk.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
As a preparative regimen prior to allogeneic or autologous hematopoietic progenitor cell transplantation:
Frequency not defined:
Central nervous system: Intracranial hemorrhage, seizure
Dermatologic: Skin rash
Gastrointestinal: Mucositis
Hematologic & oncologic: Anemia, hemorrhage, neutropenia, thrombocytopenia
Hepatic: Increased serum ALT, increased serum AST, increased serum bilirubin
Infection: Cytomegalovirus disease
Respiratory: Pneumonia
Other approved/nonapproved uses:
Frequency not defined:
Dermatologic: Alopecia, contact dermatitis, dermatitis, skin depigmentation, skin rash, urticaria
Central nervous system: Dizziness, fatigue, headache
Endocrine & metabolic: Amenorrhea
Gastrointestinal: Abdominal pain, anorexia, nausea, vomiting
Genitourinary: Cystitis, dysuria, hemorrhagic cystitis, inhibition of Spermatogenesis, urinary retention
Hypersensitivity: Anaphylactic shock, hypersensitivity reaction
Infection: Infection
Local: Pain at injection site
Neuromuscular & skeletal: Weakness
Ophthalmic: Blurred vision, conjunctivitis
Respiratory: Asthma, laryngeal edema, wheezing
Miscellaneous: Febrile reaction
<1%, postmarketing, and/or case reports: Abnormal gait, acute myelocytic leukemia, acute respiratory distress, acute sinusitis, amnesia, apathy, aphasia, arteriosclerosis (pulmonary arteriopathy), ascites, aspiration, ataxia, behavioral problems, blepharoptosis, blindness, blood coagulation disorder, blood platelet disorder (refractoriness to transfusion), bone marrow aplasia, bone marrow depression (bone marrow transplant rejection), bradycardia, brain disease, candidiasis, capillary leak syndrome, cardiac failure, cerebrovascular accident, cognitive dysfunction, coma, confusion, cranial nerve palsy, deafness, delirium, depression, diarrhea, disorientation, drowsiness, dysphagia, dyspnea on exertion, encephalitis, enterocolitis, epstein-barr infection, fever, forgetfulness, fungal infection, gastritis, gastroenteritis, gastrointestinal hemorrhage, hallucination, hematuria, hemiplegia, hepatomegaly, hyponatremia, hypotonia, immunosuppression, infection due to enterococcus, interstitial pulmonary disease, klebsiella species, lesion (including central nervous system and white matter), leukemia (recurrent), leukoencephalopathy, lower respiratory tract infection (viral), lymphoproliferative disorder (posttransplant), malaise, malignant lymphoma (including central nervous system lymphoma), malignant neoplasm (recurrence), malignant neoplasm of breast (metastatic), memory impairment, motor dysfunction, mouth disease (palatal disorder), myelodysplastic syndrome, neoplasm (metastatic), neurotoxicity, pain, papilledema, paralysis (retrobulbar), paresis (quadriparesis), pericardial effusion, pericarditis, pneumonitis, pseudomonas infection, psychomotor retardation, pulmonary aspergillosis, pulmonary disease, pulmonary hypertension, pulmonary veno-occlusive disease, pure red cell aplasia, renal failure, respiratory distress, respiratory tract infection, sepsis, septic shock, speech disturbance, staphylococcal bacteremia, staphylococcal infection, Stevens-Johnson Syndrome, strabismus, subarachnoid hemorrhage, subdural hematoma, suicidal ideation, thrombotic thrombocytopenic purpura (cerebral), toxic epidermal necrolysis, toxic nephrosis, tremor, urinary tract infection, vasodilation (cerebral ventricle), ventricular hypertrophy, weight gain
Known hypersensitivity (allergy) to thiotepa or any component of the formulation; concomitant use with live or attenuated vaccines (Tepadina).
Canadian labeling: Additional contraindications (not in the US labeling): Pregnancy; breastfeeding.
Concerns related to adverse effects:
• Bone marrow suppression: Myelosuppression (leukopenia, thrombocytopenia, and anemia) may commonly occur, particularly when used as part of the preparative regimen for hematopoietic cell transplantation (HCT) or in patients with compromised bone marrow function. Do not initiate the HCT conditioning regimen if a donor is not available. Infection or bleeding may occur; death due to septicemia and hemorrhage has occurred. Myelosuppression (including fatal cases) has also been reported with intravesicular administration (due to systemic absorption).
• CNS effects: Fatal encephalopathy has been reported in patients receiving high-dose thiotepa. Headache, apathy, psychomotor retardation, disorientation, confusion, amnesia, hallucinations, drowsiness, somnolence, seizures, coma, inappropriate behavior, and forgetfulness have also been reported (may be dose dependent). CNS toxicity, including seizures and intracranial hemorrhage was reported in pediatric patients who receive the recommended dose in combination with busulfan and cyclophosphamide as a conditioning regimen for beta thalassemia; do not exceed the recommended dose.
• Dermatologic toxicity: In patients receiving high-dose thiotepa, the parent drug and/or its active metabolites may be partially excreted through the skin. Thiotepa may cause skin discoloration, pruritus, blistering, desquamation, and peeling (may be more severe in skin folds, groin, axillae, and neck areas, and under dressings). Change occlusive dressing and clean covered skin at least twice daily during and for 48 hours after thiotepa administration (when used as a component of the HCT preparative regimen). Patients should shower/bathe in water at least twice daily through 48 hours after receiving thiotepa. Change bed sheets daily. Avoid topical creams/ointments during thiotepa therapy as to not impede excretion (Van Schandevy 2019). Accidental thiotepa exposure is also associated with skin reactions; wash skin thoroughly with soap and water and flush mucous membranes if skin and/or mucous membrane contact occurs.
• Hepatic sinusoidal obstruction syndrome: Hepatic sinusoidal obstruction syndrome (SOS, also called veno-occlusive disease [VOD]) may occur in patients receiving thiotepa in combination with busulfan and cyclophosphamide as a preparative regimen prior to HCT. Monitor for signs/symptoms of hepatic SOS through day +28 of transplant; provide supportive care if SOS develops.
• Hypersensitivity: Clinically significant hypersensitivity reactions (including anaphylaxis) have occurred.
• Secondary malignancies: Thiotepa is potentially carcinogenic; myelodysplastic syndrome and acute myeloid leukemia (AML) have been reported. There is an increased risk of secondary malignancies with thiotepa use.
Concurrent drug therapy issues:
• Vaccines: Do not administer live or attenuated viral or bacterial vaccines until the immunosuppressive effects of thiotepa have resolved.
Other warnings/precautions:
• Intrathecal safety: When used for intrathecal administration (off-label route), should not be prepared during the preparation of any other agents. After preparation, keep intrathecal medications in an isolated location or container clearly marked with a label identifying as "intrathecal" use only. Delivery of intrathecal medications to the patient should only be with other medications also intended for administration into the central nervous system (ASCO/ONS [Jacobson 2009]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection:
Generic: 15 mg (1 ea); 100 mg (1 ea)
Solution Reconstituted, Injection [preservative free]:
Tepadina: 15 mg (1 ea); 100 mg (1 ea)
Generic: 15 mg (1 ea); 100 mg (1 ea)
Yes
Solution (reconstituted) (Tepadina Injection)
15 mg (per each): $1,080.00
100 mg (per each): $5,640.00
Solution (reconstituted) (Thiotepa Injection)
15 mg (per each): $240.00 - $965.00
100 mg (per each): $2,820.00 - $5,125.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Tepadina: 15 mg (1 ea); 100 mg (1 ea)
Generic: 15 mg (1 ea); 100 mg (1 ea)
Antiemetics may be recommended to prevent nausea and vomiting; thiotepa (IV) is associated with a moderate emetic potential in adults (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
IV: Administer over 3 hours via a central line (when administering as part of the preparative regimen for hematopoietic cell transplantation in class 3 beta-thalassemia). Infusion times may vary by protocol or dose for off-label uses; refer to specific protocols. Filtering does not alter thiotepa potency. Tepadina: Administer using a 0.2 micron in-line filter; flush line prior to and after infusion with ~5 mL NS.
Intrathecal route (off-label use/route): Was administered in 10 mL (preservative free) buffered solutions (Grossman 1993).
In children, thiotepa is associated with a high emetic potential at doses ≥300 mg/m2; antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]; POGO [Paw Cho Sing 2019]). Ensure increased showers/baths conducted during therapy if applicable (see "Warnings/Precautions").
Parenteral: IV: Must be diluted prior to administration; high doses (pediatric) are administered as an IV infusion (eg, over 2- to 4-hour infusion). Infusion times may vary by protocol; refer to specific protocols. For Tepadina (and associated generic products), administer using a 0.2 micron in-line filter; flush line prior to and after infusion with ~5 mL NS.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Beta-thalassemia, class 3: To reduce the risk of graft rejection when used in conjunction with high-dose busulfan and cyclophosphamide as a preparative regimen for allogeneic hematopoietic progenitor (stem) cell transplantation in pediatric patients with class 3 beta-thalassemia.
Hematopoietic cell transplant conditioning regimen for CNS malignancy; Leptomeningeal metastases (intrathecal)
Thiotepa may be confused with thioguanine
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Intrathecal medication safety: The American Society of Clinical Oncology (ASCO)/Oncology Nursing Society (ONS) chemotherapy administration safety standards (ASCO/ONS [Jacobson 2009]) encourage the following safety measures for intrathecal chemotherapy:
• Intrathecal medication should not be prepared during the preparation of any other agents
• After preparation, keep in an isolated location or container clearly marked with a label identifying as "intrathecal" use only
• Delivery to the patient should only be with other medications also intended for administration into the central nervous system
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP2B6 Substrates (High risk with Inhibitors): Thiotepa may increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May increase serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Thiotepa. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inducers (Strong) may decrease the serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inducers. If concomitant use is unavoidable, monitor for adverse effects. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Thiotepa. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Thiotepa. Management: Avoid coadministration of thiotepa and strong CYP3A4 inhibitors. If concomitant use cannot be avoided, monitor for thiotepa adverse effects and decreased efficacy. Risk D: Consider therapy modification
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Verify pregnancy status prior to therapy initiation in patients who could become pregnant. Effective contraception should be used during treatment and for at least 6 months after the final dose. Patients with partners who could become pregnant should use effective contraception during therapy and for at least 1 year after the final dose.
Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to thiotepa may cause fetal harm.
It is not known if thiotepa is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.
CBC with differential and platelet count frequently throughout therapy; renal and liver function tests (monitor serum transaminases and bilirubin through day +28 of transplant). Verify pregnancy status prior to treatment in patients who could become pregnant. Monitor for signs/symptoms of hypersensitivity reactions (monitor through resolution of symptoms), bleeding, infection, dermatologic toxicity, hepatic sinusoidal obstruction syndrome (monitor through day +28 of transplant), and CNS toxicity. Monitor for development of secondary malignancies.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Thiotepa is an alkylating agent which produces cross-linking of DNA strands leading to inhibition of DNA, RNA, and protein synthesis; thiotepa is cell-cycle independent (Perry 2012)
Distribution: Vdss: 0.3 to 1.6 L/kg; penetrates into CSF (Maanen 2000); the mean volume of distribution following a single IV dose in pediatric patients receiving a 5 mg/kg dose was 1.2 L/kg or 30 L/m2.
Protein binding: ~10% to 20%.
Metabolism: Extensively hepatic via cytochrome P450 system, primarily to the major (active) metabolite TEPA (Maanen 2000; Perry 2012).
Half-life elimination: Terminal:
Pediatrics (5 mg/kg IV dose): Thiotepa: 1.7 hours; TEPA: 4 hours.
Adults (20 mg to 250 mg/m2 IV dose): Thiotepa: 1.4 to 3.7 hours; TEPA: 4.9 to 17.6 hours.
Excretion: Urine (<2% of thiotepa dose; <11% of TEPA); dermal via sweat (Horn 1989).
Altered kidney function: Thiotepa and TEPA exposure increased 1.5-fold and 2.6-fold, respectively, following administration of multiple doses of 120 mg/m2/day in a patient with moderate renal impairment (CrCl 38 mL/minute), compared to patients with normal renal function.
Hepatic function impairment: In two adult patients with liver metastases and moderate hepatic impairment receiving multiple thiotepa doses of 7 mg/kg (administered every 2 days with cyclophosphamide), thiotepa exposure increased by 1.6-fold and 1.8-fold compared to a patient with normal hepatic function.
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