TEPADINA

Ethylene Imines

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Immediately wash the skin thoroughly with soap and water if the thiotepa solution contacts the skin. If mucous membranes are exposed, flush the area thoroughly with water.
Emetic Risk
Moderate
Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
Nonvesicant

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Reconstitution:
Using a syringe fitted with a needle, add 1.5 mL of Sterile Water for Injection to the 15-mg vial and 10 mL of Sterile Water for Injection to the 100-mg vial for a final concentration of about 10 mg/mL; mix manually by repeated inversions.
Storage following reconstitution: contents of vial are stable for 8 hours when stored in the refrigerator (2 to 8 degrees C; 36 to 46 degrees F).
Dilution:
The reconstituted solution is hypotonic and should be further diluted before use.
Add the appropriate volume for the calculated dose to an infusion bag of 0.9% Sodium Chloride Injection for a final concentration between 0.5 and 1 mg/mL.
Filter using a 0.2-micron filter prior to administration.
Storage following dilution: use immediately if possible; admixture is stable for 24 hours when stored in the refrigerator (2 to 8 degrees C; 36 to 46 degrees F) and for 4 hours when stored at 25 degrees C (77 degrees F).

Intravenous infusion:
Administer using an infusion set equipped with a 0.2 micron in-line filter.
Flush the catheter with approximately 5 mL of 0.9% Sodium Chloride Injection prior to and after each infusion.

Intracavitary instillation:
Administration is typically through the same tubing which is used to remove the fluid from the involved cavity.
 
Intravesical instillation:
Patients should be dehydrated for 8 to 12 hours prior to treatment.
Mix 60 mg of thiotepa in 30 to 60 mL 0.9% Sodium Chloride Injection and instill into the bladder via catheter.
The solution should be retained for 2 hours; use a reduced volume of 30 mL for patients who cannot retain 60 mL for 2 hours.
Reposition the patient every 15 minutes for maximum tumor contact.

graft-versus-host disease (GVHD) / Delayed / 28.0-35.0
elevated hepatic enzymes / Delayed / 0-24.0
hemorrhagic cystitis / Delayed / 0-20.0
stomatitis / Delayed / 16.0-16.0
hyperbilirubinemia / Delayed / 0-16.0
exfoliative dermatitis / Delayed / 0-12.0
intracranial bleeding / Delayed / 8.0-8.0
infection / Delayed / 0-4.0
GI bleeding / Delayed / 4.0-4.0
veno-occlusive disease (VOD) / Delayed / 0-4.0
sinusoidal obstruction syndrome (SOS) / Delayed / 0-4.0
laryngeal edema / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
visual impairment / Early / Incidence not known
papilledema / Delayed / Incidence not known
enterocolitis / Delayed / Incidence not known
stroke / Early / Incidence not known
seizures / Delayed / Incidence not known
coma / Early / Incidence not known
leukoencephalopathy / Delayed / Incidence not known
cranial nerve palsies / Delayed / Incidence not known
leukemia / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
lymphoma / Delayed / Incidence not known
breast cancer / Delayed / Incidence not known
post-transplant lymphoproliferative disorder (PTLD) / Delayed / Incidence not known
pericarditis / Delayed / Incidence not known
bradycardia / Rapid / Incidence not known
cardiac arrest / Early / Incidence not known
heart failure / Delayed / Incidence not known
pericardial effusion / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
capillary leak syndrome / Early / Incidence not known
suicidal ideation / Delayed / Incidence not known
respiratory arrest / Rapid / Incidence not known
pulmonary hypertension / Delayed / Incidence not known
pulmonary toxicity / Early / Incidence not known

hematuria / Delayed / 20.0-20.0
bleeding / Early / 20.0-20.0
palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / 0-12.0
neutropenia / Delayed / Incidence not known
bone marrow suppression / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
wheezing / Rapid / Incidence not known
urinary retention / Early / Incidence not known
dysuria / Early / Incidence not known
cystitis / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
conjunctivitis / Delayed / Incidence not known
blurred vision / Early / Incidence not known
dysphagia / Delayed / Incidence not known
gastritis / Delayed / Incidence not known
aphasia / Delayed / Incidence not known
confusion / Early / Incidence not known
hypotonia / Delayed / Incidence not known
memory impairment / Delayed / Incidence not known
hallucinations / Early / Incidence not known
encephalopathy / Delayed / Incidence not known
neurotoxicity / Early / Incidence not known
amnesia / Delayed / Incidence not known
prolonged bleeding time / Delayed / Incidence not known
subdural hematoma / Early / Incidence not known
hepatomegaly / Delayed / Incidence not known
ascites / Delayed / Incidence not known
immunosuppression / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
delirium / Early / Incidence not known
depression / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known
dyspnea / Early / Incidence not known

diarrhea / Early / 24.0-24.0
pruritus / Rapid / 0-12.0
maculopapular rash / Early / 0-12.0
rash / Early / 0-12.0
urticaria / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
ptosis / Delayed / Incidence not known
nausea / Early / Incidence not known
anorexia / Delayed / Incidence not known
vomiting / Early / Incidence not known
abdominal pain / Early / Incidence not known
headache / Early / Incidence not known
drowsiness / Early / Incidence not known
tremor / Early / Incidence not known
dizziness / Early / Incidence not known
fatigue / Early / Incidence not known
malaise / Early / Incidence not known
weakness / Early / Incidence not known
spermatogenesis inhibition / Delayed / Incidence not known
amenorrhea / Delayed / Incidence not known
fever / Early / Incidence not known
sinusitis / Delayed / Incidence not known
influenza / Delayed / Incidence not known
weight gain / Delayed / Incidence not known

Severe bone marrow suppression (e.g., anemia, neutropenia, thrombocytopenia) has been reported with thiotepa therapy. Fatalities due to infection (e.g., sepsis) and bleeding (e.g., intracranial bleeding) have occurred; death due to myelosuppression has also been reported following intravesical administration of thiotepa due to systemic absorption. Monitor complete blood counts (CBC) during therapy and provide supportive care (e.g., antiinfective therapy, blood or platelet transfusions) as necessary and until there is adequate hematopoietic recovery. Profound myelosuppression occurs when thiotepa is used as part of high-dose chemotherapy prior to an allogeneic hematopoietic progenitor cell transplantation in patients with class 3 beta-thalassemia. Do not begin the preparative regimen until a stem-cell donor is available. Patients with malignant effusions or breast, ovarian, or bladder cancer who have received prior radiation therapy and/or chemotherapy are at increased risk for severe myelosuppression with thiotepa. In these patients, monitor CBC weekly during therapy and for at least 3 weeks after the end of therapy. A dosage reduction may be required in patients who have rapidly falling blood or platelet counts; consider discontinuing therapy if the white blood cell count falls to 3,000 cells/mm3 or less or the platelet count falls below 150,000 cells/mm3 or less.

There is some evidence that thiotepa is carcinogenic in humans; therefore, patients who receive thiotepa may have an increased risk of developing a new primary malignancy. Lymphoma, leukemia, post-transplant lymphoproliferative disorder, and myelodysplastic syndromes have been reported in patients who received thiotepa as part of high-dose chemotherapy prior to allogeneic or autologous hematopoietic stem-cell transplantation in adult and pediatric patients.

TEPADINA

Rx

Alkylating antineoplastic agent
Used for treatment of bladder cancer, ovarian cancer, breast cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, secondary intracavitary malignant effusions, and to reduce the risk of graft rejection when used as part of a preparative regimen for allogeneic hematopoietic progenitor cell transplantation in pediatric patients with class 3 beta-thalassemia
There is an increased risk of a secondary malignancy with thiotepa use

0.3 to 0.4 mg/kg IV repeated every 1 to 4 weeks. Adjust the maintenance dose weekly based on blood counts; do not administer maintenance doses more frequently than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

60 mg intravesically once weekly for 4 weeks. The treatment course may be repeated if necessary; however, second and third courses should be given with caution as the risk of bone marrow depression is increased. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

0.3 to 0.4 mg/kg IV repeated every 1 to 4 weeks. Adjust the maintenance dose weekly based on blood counts; do not administer maintenance doses more frequently than once weekly. The use of thiotepa for the treatment of Hodgkin lymphoma is now largely superseded by other treatments. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Doses of 20 to 40 mg/m2 IV every 3 to 4 weeks in combination with other agents or 0.3 to 0.4 mg/kg IV every 1 to 4 weeks as a single agent. Thiotepa 20 mg/m2 IV once every 21 days with mitoxantrone, prednisone, and vincristine has been used in patients older than 65 years. In older patients with CNS lymphoma, thiotepa has been given in a dose of 40 mg/m2 IV every 4 weeks along with procarbazine, and vincristine, and IV and intrathecal methotrexate. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

0.6 to 0.8 mg/kg instilled into the malignant effusion once every 1 to 4 weeks. Adjust the maintenance dose weekly based on blood counts; do not administer maintenance doses more frequently than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

0.3 to 0.4 mg/kg IV repeated every 1 to 4 weeks. Adjust the maintenance dose weekly based on blood counts; do not administer maintenance doses more frequently than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[61718]

5 mg/kg IV over 3 hours (via a central venous catheter) approximately 12 hours apart for 2 doses on day -6 prior to an allogeneic hematopoietic progenitor cell transplantation (HSCT) in combination with high-dose busulfan and cyclophosphamide. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a retrospective analysis in pediatric patients (n = 25; median age, 10 years; range, 5 to 16 years; human leukocyte antigen (HLA)-identical sibling donor, 100%) with class 3 beta-thalassemia, no patients experienced acute or late graft rejection following treatment with thiotepa, busulfan (weight-based IV dosing for 4 days (16 total doses) on days -10 to -7), and cyclophosphamide (40 mg/kg daily for 4 days on days -5 to -2) as a preparatory regimen for an allogeneic HSCT compared with 25.5% of historical control patients (n = 51) who experienced graft rejection after receiving busulfan and cyclophosphamide only. Weight-based busulfan was dosed as follows: 1 mg/kg every 6 hours for patients who weighed less than 9 kg; 1.2 mg/kg every 6 hours for patients who weighed 9 to 16 kg; 1.1 mg/kg every 6 hours for patients who weighed 16.1 to 23 kg; 0.95 mg/kg every 6 hours for patients who weighed 23.1 to 34 kg; and 0.8 mg/kg every 6 hours for patients who weighed more than 34 kg. All patients had previously received cytoreduction therapy with hydroxyurea, azathioprine, and fludarabine.[61718] Primary graft failure was defined as failure to achieve an absolute neutrophil count (ANC) higher than 0.5 x 109 cells/L by day 28 and the presence of less than 10% of donor cells according to a bone marrow chimerism assay. Secondary graft failure was defined as donor engraftment followed by evidence of graft loss by a persistent drop in ANC to less than 0.5 x 109 cells/L, loss of donor chimerism in bone marrow or peripheral blood, and the resumption of red blood cell transfusion dependence.[61746]

10 mg intrathecally twice weekly (days 1 and 4) for 8 weeks has been studied. Intrathecal thiotepa was compared with intrathecal methotrexate in a randomized trial in 52 patients with previously untreated neoplastic meningitis. Patients in this study had a solid tumor (breast cancer, n = 25; lung cancer, n = 12; other, n = 4) or lymphoma (n = 10) as the primary tumor type. The median overall survival times were 14.1 weeks in the thiotepa arm and 15.9 weeks in the methotrexate arm. After 8 weeks of therapy, no patient experienced a complete response or improvement. Eight patients in each treatment arm converted from a positive to a negative cytology after therapy. Patients in the thiotepa arm experienced significantly less neurologic (p < 0.008) and skin/mucous membrane (p = 0.042) toxicity compared with the methotrexate arm. Serious toxicities reported with thiotepa included bacterial meningitis resulting in death (n = 1), grade 4 hematologic toxicity (n = 2), and respiratory arrest (n = 1).

250 mg/m2 per day IV over 4 hours for 3 days in combination with busulfan (1 mg/kg PO every 6 hours for a total of 10 or 12 doses) and cyclophosphamide (60 mg/kg IV for 2 days) (with mesna) (TCB regimen) has been studied as a conditioning regimen prior to autologous or allogeneic transplantation in several nonrandomized studies. In these studies, 3- to 5-year overall survival rates ranged from 26% to 29%, and overall response rates ranged from 78% to 81%. Supportive care medications included prophylactic antibiotic/antifungal/antiviral agents, phenytoin (to prevent busulfan-related seizures), granulocyte colony-stimulating factors, and graft-versus-host disease prophylaxis. Regimen-related toxicity (RRT) was evaluated in a nonrandomized study in 127 adult patients with hematologic malignancies who received TBC as a conditioning regimen prior to autologous or allogeneic transplantation. Grade 3 or 4 RRT (using the Fred Hutchinson Cancer Research Center toxicity grading system) occurred in 19 patients (15%). Treatment-related mortality (TRM) was 17% at 30 days post-transplant and 33% at 120 days post-transplant, and the estimated regimen-related death was 8%. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

250 mg/m2 per day IV over 4 hours on days -9, -8, and -7 in combination with busulfan (1 mg/kg orally every 6 hours on days -6, -5, and -4 for a total of 12 doses) and cyclophosphamide (60 mg/kg IV on days -3 and -2) prior to autologous or allogeneic transplantation resulted in a 3-year event-free survival rate of 51% in a small, nonrandomized study in 17 pediatric patients 1.6 to 18 years of age. Eleven patients received the first dose of busulfan at 40 mg/m2 orally and then subsequent doses were based on the initial dose pharmacokinetics with a target AUC of 1,000 to 1,500 micromol times minute/L. In this study, the grade 3 or 4 regimen-related toxicity was 12%, and the 3-year treatment-related mortality was 43%. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Dose is not established; 65 mg/m2 IV bolus over 5 minutes on day 1 repeated every 21 days for 1 year or until disease progression has been studied with no response. Thiotepa was administered to 66 patients younger than age 21 years of with recurrent Ewing's sarcoma, peripheral neuroectodermal tumors, rhabdomyosarcoma, and other undifferentiated tumors, spindle-cell tumors (including osteosarcoma, fibrosarcoma, and hemangiosarcoma), or other solid tumors (including neuroblastoma, hepatoblastoma, and Wilms' tumor) in a nonrandomized, phase II study. No patient with soft-tissue sarcoma responded to thiotepa therapy. Grade 3 or 4 neutropenia and thrombocytopenia were reported in 35% and 38% of thiotepa courses, respectively; additionally, febrile neutropenia was reported in 34% of courses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

†Indicates off-label use

Increased thiotepa exposure was observed in patients with moderate hepatic impairment (bilirubin levels greater than 1.5 to 3-times the upper limit of normal and any AST level); however, the manufacturer does not recommend a thiotepa dosage adjustment in patients with hepatic impairment. The effects of severe hepatic impairment on thiotepa exposure are not known.

Increased thiotepa exposure was observed in patients with moderate renal impairment (creatinine clearance, 30 to 59 mL/min); however, the manufacturer does not recommend a thiotepa dosage adjustment in patients with renal impairment. The effects of severe renal impairment or end-stage renal disease on thiotepa exposure are not known.

Adagrasib: (Major) Avoid the concomitant use of thiotepa and adagrasib if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A to the active metabolite, TEPA; adagrasib is a strong CYP3A inhibitor.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid the concomitant use of thiotepa and clarithromycin if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; clarithromycin is a strong CYP3A4 inhibitor.
Apalutamide: (Major) Avoid the concomitant use of thiotepa and apalutamide if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; apalutamide is a strong CYP3A4 inducer.
Atazanavir: (Major) Avoid the concomitant use of thiotepa and atazanavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; atazanavir is a strong CYP3A4 inhibitor.
Atazanavir; Cobicistat: (Major) Avoid the concomitant use of thiotepa and atazanavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; atazanavir is a strong CYP3A4 inhibitor. (Major) Avoid the concomitant use of thiotepa and cobicistat if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; cobicistat is a strong CYP3A4 inhibitor.
Bupropion: (Moderate) The concomitant use of thiotepa and bupropion may increase the exposure of bupropion but decrease hydroxybupropion exposure; however, the clinical relevance of this interaction is unknown. Dosage adjustment of bupropion may be necessary based on clinical response. Thiotepa is a CYP2B6 inhibitor in vitro; bupropion is a sensitive substrate of CYP2B6 in vitro.
Bupropion; Naltrexone: (Moderate) The concomitant use of thiotepa and bupropion may increase the exposure of bupropion but decrease hydroxybupropion exposure; however, the clinical relevance of this interaction is unknown. Dosage adjustment of bupropion may be necessary based on clinical response. Thiotepa is a CYP2B6 inhibitor in vitro; bupropion is a sensitive substrate of CYP2B6 in vitro.
Carbamazepine: (Major) Avoid the concomitant use of thiotepa and carbamazepine if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; carbamazepine is a strong CYP3A4 inducer.
Ceritinib: (Major) Avoid the concomitant use of thiotepa and ceritinib if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; ceritinib is a strong CYP3A4 inhibitor.
Chloramphenicol: (Major) Avoid the concomitant use of thiotepa and chloramphenicol if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; chloramphenicol is a strong CYP3A4 inhibitor.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Clarithromycin: (Major) Avoid the concomitant use of thiotepa and clarithromycin if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; clarithromycin is a strong CYP3A4 inhibitor.
Cobicistat: (Major) Avoid the concomitant use of thiotepa and cobicistat if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; cobicistat is a strong CYP3A4 inhibitor.
Cyclophosphamide: (Moderate) The concomitant use of thiotepa and cyclophosphamide may reduce cyclophosphamide metabolism to its active metabolite resulting in decreased cyclophosphamide efficacy. Thiotepa is a CYP2B6 inhibitor in vitro. Cyclophosphamide is converted to the active metabolite, 4-hydroxycyclophosphamide, via CYP2B6 metabolism. This effect appears to be sequence dependent with a greater reduction in the conversion to the active metabolite when thiotepa is given 1.5 hours prior to the IV cyclophosphamide compared to when thiotepa is given after IV cyclophosphamide.
Darunavir: (Major) Avoid the concomitant use of thiotepa and darunavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; darunavir is a strong CYP3A4 inhibitor.
Darunavir; Cobicistat: (Major) Avoid the concomitant use of thiotepa and cobicistat if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; cobicistat is a strong CYP3A4 inhibitor. (Major) Avoid the concomitant use of thiotepa and darunavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; darunavir is a strong CYP3A4 inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid the concomitant use of thiotepa and cobicistat if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; cobicistat is a strong CYP3A4 inhibitor. (Major) Avoid the concomitant use of thiotepa and darunavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; darunavir is a strong CYP3A4 inhibitor.
Delavirdine: (Major) Avoid the concomitant use of thiotepa and delavirdine if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; delavirdine is a strong CYP3A4 inhibitor.
Dextromethorphan; Bupropion: (Moderate) The concomitant use of thiotepa and bupropion may increase the exposure of bupropion but decrease hydroxybupropion exposure; however, the clinical relevance of this interaction is unknown. Dosage adjustment of bupropion may be necessary based on clinical response. Thiotepa is a CYP2B6 inhibitor in vitro; bupropion is a sensitive substrate of CYP2B6 in vitro.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid the concomitant use of thiotepa and cobicistat if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; cobicistat is a strong CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid the concomitant use of thiotepa and cobicistat if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; cobicistat is a strong CYP3A4 inhibitor.
Enzalutamide: (Major) Avoid the concomitant use of thiotepa and enzalutamide if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; enzalutamide is a strong CYP3A4 inducer.
Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
Fosamprenavir: (Major) Avoid the concomitant use of thiotepa and fosamprenavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; fosamprenavir is a strong CYP3A4 inhibitor.
Fosphenytoin: (Major) Avoid the concomitant use of thiotepa and fosphenytoin if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A to the active metabolite, TEPA; fosphenytoin is a strong CYP3A inducer.
Grapefruit juice: (Major) Avoid the concomitant use of thiotepa and grapefruit juice; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; grapefruit juice is a strong CYP3A4 inhibitor.
Idelalisib: (Major) Avoid the concomitant use of thiotepa and idelalisib if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; idelalisib is a strong CYP3A4 inhibitor.
Indinavir: (Major) Avoid the concomitant use of thiotepa and indinavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; indinavir is a strong CYP3A4 inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid the concomitant use of thiotepa and rifampin if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; rifampin is a strong CYP3A4 inducer.
Isoniazid, INH; Rifampin: (Major) Avoid the concomitant use of thiotepa and rifampin if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; rifampin is a strong CYP3A4 inducer.
Itraconazole: (Major) Avoid the concomitant use of thiotepa and itraconazole if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; itraconazole is a strong CYP3A4 inhibitor.
Ketoconazole: (Major) Avoid the concomitant use of thiotepa and ketoconazole if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; ketoconazole is a strong CYP3A4 inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid the concomitant use of thiotepa and clarithromycin if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; clarithromycin is a strong CYP3A4 inhibitor.
Letermovir: (Moderate) The concomitant use of thiotepa and letermovir may result in reduced metabolism to the active thiotepa metabolite and decreased thiotepa efficacy. Avoid concomitant use if letermovir is used in combination with cyclosporine and consider an alternative agent with no or minimal potential to inhibit CYP3A4; monitor patients for signs of reduced thiotepa efficacy if coadministration is necessary, In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Levoketoconazole: (Major) Avoid the concomitant use of thiotepa and ketoconazole if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; ketoconazole is a strong CYP3A4 inhibitor.
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Lonafarnib: (Major) Avoid the concomitant use of thiotepa and lonafarnib if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; lonafarnib is a strong CYP3A4 inhibitor.
Lopinavir; Ritonavir: (Major) Avoid the concomitant use of thiotepa and ritonavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; ritonavir is a strong CYP3A4 inhibitor.
Lumacaftor; Ivacaftor: (Major) Avoid the concomitant use of thiotepa and lumacaftor; ivacaftor if possible because increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA. Lumacaftor; ivacaftor is a strong CYP3A4 inducer.
Lumacaftor; Ivacaftor: (Major) Avoid the concomitant use of thiotepa and lumacaftor; ivacaftor if possible because increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA. Lumacaftor; ivacaftor is a strong CYP3A4 inducer.
Methadone: (Moderate) The concomitant use of thiotepa and methadone may increase the exposure of methadone; however, the clinical relevance of this interaction is unknown. Thiotepa is a CYP2B6 inhibitor in vitro; methadone is a CYP2B6 substrate.
Mifepristone: (Major) Avoid the concomitant use of thiotepa and chronic use of mifepristone if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; mifepristone is a strong CYP3A4 inhibitor.
Mitotane: (Major) Avoid the concomitant use of thiotepa and mitotane if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; mitotane is a strong CYP3A4 inducer.
Mivacurium: (Moderate) Concomitant use of mivacurium and thiotepa may prolong neuromuscular blockade. It has been theorized that this is caused by the anticholinesterase activity of anticancer drugs such as thiotepa.
Nefazodone: (Major) Avoid the concomitant use of thiotepa and nefazodone if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; nefazodone is a strong CYP3A4 inhibitor.
Nelfinavir: (Major) Avoid the concomitant use of thiotepa and nelfinavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; nelfinavir is a strong CYP3A4 inhibitor.
Nicotine: (Moderate) The concomitant use of thiotepa and nicotine may increase the exposure of nicotine; however, the clinical relevance of this interaction is unknown. Thiotepa is a CYP2B6 inhibitor in vitro; nicotine is a CYP2B6 substrate.
Nirmatrelvir; Ritonavir: (Major) Avoid the concomitant use of thiotepa and ritonavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; ritonavir is a strong CYP3A4 inhibitor.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert their toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Phenobarbital: (Major) Avoid the concomitant use of thiotepa and phenobarbital if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; phenobarbital is a strong CYP3A4 inducer.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid the concomitant use of thiotepa and phenobarbital if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; phenobarbital is a strong CYP3A4 inducer.
Phenytoin: (Major) Avoid the concomitant use of thiotepa and phenytoin if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; phenytoin is a strong CYP3A4 inducer.
Posaconazole: (Major) Avoid the concomitant use of thiotepa and posaconazole if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; posaconazole is a strong CYP3A4 inhibitor.
Primidone: (Major) Avoid the concomitant use of thiotepa and primidone if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; primidone is a strong CYP3A4 inducer.
Ribociclib: (Major) Avoid the concomitant use of thiotepa and ribociclib if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; ribociclib is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Major) Avoid the concomitant use of thiotepa and ribociclib if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; ribociclib is a strong CYP3A4 inhibitor.
Rifampin: (Major) Avoid the concomitant use of thiotepa and rifampin if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; rifampin is a strong CYP3A4 inducer.
Ritonavir: (Major) Avoid the concomitant use of thiotepa and ritonavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; ritonavir is a strong CYP3A4 inhibitor.
Saquinavir: (Major) Avoid the concomitant use of thiotepa and saquinavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; saquinavir is a strong CYP3A4 inhibitor.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Sofosbuvir; Velpatasvir: (Moderate) The concomitant use of thiotepa and velpatasvir may increase the exposure of velpatasvir; however, the clinical relevance of this interaction is unknown. Thiotepa is a CYP2B6 inhibitor in vitro; velpatasvir is a CYP2B6 substrate.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) The concomitant use of thiotepa and velpatasvir may increase the exposure of velpatasvir; however, the clinical relevance of this interaction is unknown. Thiotepa is a CYP2B6 inhibitor in vitro; velpatasvir is a CYP2B6 substrate.
St. John's Wort, Hypericum perforatum: (Major) Avoid the concomitant use of thiotepa and St. John's Wort if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; St. John's Wort is a strong CYP3A4 inducer.
Stiripentol: (Moderate) Consider a dose adjustment of thiotepa when coadministered with stiripentol. Coadministration may alter plasma concentrations of thiotepa resulting in an increased risk of adverse reactions and/or decreased efficacy. Thiotepa is a CYP2B6 substrate. In vitro data predicts inhibition or induction of CYP2B6 by stiripentol potentially resulting in clinically significant interactions.
Succinylcholine: (Moderate) Concomitant use of succinylcholine and thiotepa may prolong neuromuscular blockade. It has been theorized that this is caused by the anticholinesterase activity of anticancer drugs such as thiotepa.
Tipranavir: (Major) Avoid the concomitant use of thiotepa and tipranavir if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; tipranavir is a strong CYP3A4 inhibitor.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Tucatinib: (Major) Avoid the concomitant use of thiotepa and tucatinib if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; tucatinib is a strong CYP3A4 inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid the concomitant use of thiotepa and clarithromycin if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; clarithromycin is a strong CYP3A4 inhibitor.
Voriconazole: (Major) Avoid the concomitant use of thiotepa and voriconazole if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; voriconazole is a strong CYP3A4 inhibitor.

TEPADINA/Thiotepa Intracavitary Inj Pwd F/Sol: 15mg, 100mg
TEPADINA/Thiotepa Intravenous Inj Pwd F/Sol: 15mg, 100mg
TEPADINA/Thiotepa Intravesical Inj Pwd F/Sol: 15mg, 100mg

0.8 mg/kg intracavitary; 60 mg intravesically; 0.4 mg/kg IV; high IV doses (e.g., 250 mg/m2) have been used off-label as part of high-dose chemotherapy prior to a bone marrow transplantation.

0.8 mg/kg intracavitary; 60 mg intravesically; 0.4 mg/kg IV; high IV doses (e.g., 250 mg/m2) have been used off-label as part of high-dose chemotherapy prior to a bone marrow transplantation in patients less than 68 years.

5 mg/kg IV for 2 doses; high IV doses (e.g., 250 mg/m2) have been used off-label as part of high-dose chemotherapy prior to a bone marrow transplantation.

5 mg/kg IV for 2 doses; high IV doses (e.g., 250 mg/m2) have been used off-label as part of high-dose chemotherapy prior to a bone marrow transplantation.

5 mg/kg IV for 2 doses.

Thiotepa is a polyfunctional alkylating agent, related chemically and pharmacologically to a nitrogen mustard compound. It disrupts the bonds of DNA by releasing ethylenimine radicals acting like irradiation. A main bond disruption is caused by the alkylation of guanine at the N-7 position that severs the link between the purine base and sugar releasing alkylated guanines.

Thiotepa is administered intravenously (IV) or via intravesical or intracavitary instillation. It is approximately 10% to 20% bound to plasma proteins. Following the administration of thiotepa 20 mg to 250 mg/m2 as an IV bolus or up to a 4-hour IV infusion in adults, the mean volume of distribution ranged from 1 to 1.9 L/kg, the mean clearance ranged from 14.6 to 27.9 L/hr/m2, and the mean terminal elimination half-life ranged from 1.4 to 3.7 hours for thiotepa and 4.9 to 17.6 hours for its major active metabolite, N,N',N''triethylenephosphoramide (TEPA). Thiotepa pharmacokinetic parameters were evaluated in 13 patients with advanced ovarian cancer (age range, 45 to 84 years). The elimination half-life values (+/- the standard error of the mean (SEM)) following thiotepa 60 mg IV and 80 mg IV were 2.4 +/- 0.3 and 2.3 +/- 0.3 hours, respectively, for thiotepa; additionally, the elimination half-life values were 17.6 +/- 3.6 and 15.7 +/- 2.7 hours, respectively, for TEPA. The parent drug total body clearance values were 446 +/- 63 and 419 +/- 56 mL/min following thiotepa 60 mg IV and 80 mg IV, respectively. Thiotepa undergoes hepatic metabolism. Urinary excretion of thiotepa accounts for less than 2% of the dose and TEPA accounted for 11% or less of the dose.
Affected cytochrome P450 isoenzymes: CYP3A4 and CYP2B6
In vitro data suggests that thiotepa is metabolized to TEPA via CYP3A4 and CYP2B6 and that it is a CYP2B6 inhibitor. Avoid concomitant use with strong CYP3A4 inhibitors or inducers; thiotepa levels and risk of toxicity may increase. Consider alternative medications with no or minimal potential to inhibit or induce CYP3A4. If concomitant use of strong CYP3A4 inhibitors or inducers cannot be avoided, closely monitor patients for adverse drug reactions. Although thiotepa may increase the levels of CYP2B6 substrates, the clinical relevance of this interaction is not known.

Thiotepa pharmacokinetic parameters were evaluated in 13 patients with advanced ovarian cancer (age range, 45 to 84 years). The Cmax values (+/- the standard error of the mean (SEM)) following thiotepa 60 mg IV and 80 mg IV were 1,331 +/- 119 and 1,828 +/- 135 ng/mL, respectively, for thiotepa; additionally, the Cmax values were 273 +/- 46 and 353 +/- 46 ng/mL, respectively, for TEPA. The AUC values (+/- (SEM) following thiotepa 60 mg IV and 80 mg IV were 2,832 +/- 412 and 4,127 +/- 668 ng x hour/mL, respectively, for thiotepa; additionally, the AUC values were 4,789 +/- 1,022 and 7,452 +/- 1,667 ng x hour/mL, respectively, for TEPA.

Thiotepa may cause fetal harm when administered to a pregnant woman, based on its mechanism of action and animal studies. Advise females of reproductive potential to avoid pregnancy while taking thiotepa. Discuss the potential hazard to the fetus if thiotepa is used during pregnancy or if a patient becomes pregnant while taking this drug. Embryo-fetal toxicities including neural tube defects and malformations of the skeletal system were observed in animal reproduction studies in mice and rats at doses up to the maximum recommended human daily dose (based on body-surface area). Additionally, thiotepa was lethal to rabbit fetuses at approximately 2-times the maximum recommended human therapeutic dose.

No information is available regarding the presence of thiotepa in human milk, the effects on the breastfed infant, or the effects on milk production. Due to the potential for serious adverse reactions in the nursing infant, breast-feeding is not recommended during thiotepa therapy.