TEPADINA® (thiotepa) for Injection

This page is intended for U.S. healthcare professionals only. Patients should consult a physician to discuss whether this product is suitable for them. 

Available through wholesalers and distributors in 100 mg and 15 mg single-dose vials as well as 200 mg multi chamber bags

• For intravenous, intracavitary or intravesical use
• See important safety information and full prescribing information below
• Larger vial size accommodates higher doses:

Number of vials required for dose*

*Applicable only for the indication: 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 (HSCT) for pediatric patients with class 3 beta-thalassemia. See complete list of indications and important safety information.

Order through your wholesaler or distributor using the NDCs below.

• TEPADINA 15 mg vial: NDC 70121-1630-1
• TEPADINA 100 mg vial: NDC 70121-1631-1
• TEPADINA 200 mg bag: NDC 70121-2749-1

Preservative free; not made with natural rubber latex

Order from your wholesaler or contact Amneal: Toll Free 866.525.7270 | CustomerRelations@amneal.com

Important Safety Information

CONTRAINDICATIONS

TEPADINA is contraindicated in patients with severe hypersensitivity to thiotepa and in concomitant use with live or attenuated vaccines.

WARNINGS AND PRECAUTIONS

• Myelosuppression: The consequence of treatment with high doses of TEPADINA together with other chemotherapy at the recommended dose and schedule in the preparative regimen for class 3 beta- thalassemia is profound myelosuppression occurring in all patients. Do not begin the preparative regimen if a stem cell donor is not available. Monitor complete blood counts, and provide supportive care for infections, anemia and thrombocytopenia until there is adequate hematopoietic recovery. For patients receiving TEPADINA for treatment of adenocarcinoma of the breast, adenocarcinoma of the ovary, malignant effusions and superficial papillary carcinoma of the urinary bladder, if the bone marrow has been compromised by prior irradiation or chemotherapy, or is recovering from chemotherapy, the risk of severe myelosuppression with TEPADINA may be increased. Perform periodic complete blood counts during the course of treatment with TEPADINA. Provide supportive care for infections, bleeding, and symptomatic anemia. Inform patients of the possibility of developing low blood cell counts and the need for hematopoietic progenitor cell infusion. Instruct patients to immediately report to their healthcare provider if bleeding or fever occurs.
• Hypersensitivity: Clinically significant hypersensitivity reactions, including anaphylaxis, have occurred following administration of TEPADINA. If anaphylactic or other clinically significant allergic reaction occurs, discontinue treatment with TEPADINA, initiate appropriate therapy, and monitor until signs and symptoms resolve. Counsel patients on the signs and symptoms of hypersensitivity and to seek immediate emergency assistance if they develop any of these signs and symptoms.
• Cutaneous Toxicity: TEPADINA and/or its active metabolites may be excreted in part via skin patients receiving high-dose therapy. Treatment with TEPADINA may cause skin discoloration, pruritus, blistering, desquamation, and peeling that may be more severe in the groin, axillae, skin folds, in the neck area, and under dressings. Instruct patients to shower or bathe with water at least twice daily through 48 hours after administration of TEPADINA. Change occlusive dressing and clean the covered skin at least twice daily through 48 hours after administration of TEPADINA. Change bed sheets daily during treatment. Skin reactions associated with accidental exposure to TEPADINA may also occur. Wash the skin thoroughly with soap and water in case TEPADINA solution contacts the skin. Flush mucous membranes in case of TEPADINA contact with mucous membranes.
• Concomitant Use of Live and Attenuated Vaccines: Do not administer live or attenuated viral or bacterial vaccines to a patient treated with TEPADINA until the immunosuppressive effects have resolved.
• Hepatic Veno-Occlusive Disease: Hepatic veno-occlusive disease may occur in patients who have received high-dose TEPADINA in conjunction with busulfan and cyclophosphamide. Monitor by physical examination, serum transaminases and bilirubin daily through BMT Day +28, and provide supportive care to patients who develop hepatic veno-occlusive disease.
• Central Nervous System Toxicity: Fatal encephalopathy has occurred in patients treated with high doses of thiotepa. Other central nervous system toxicities, such as headache, apathy, psychomotor retardation, disorientation, confusion, amnesia, hallucinations, drowsiness, somnolence, seizures, coma, inappropriate behavior and forgetfulness have been reported to occur in a dose-dependent manner during or shortly after administration of high-dose thiotepa. In pediatric patients treated with TEPADINA at the recommended dose in combination with busulfan and cyclophosphamide, 8% developed central nervous system toxicity (seizures and intracranial hemorrhage). Do not exceed the recommended dose of TEPADINA. If severe or life-threatening central nervous system toxicity occurs, discontinue administration of TEPADINA and provide supportive care.
• Carcinogenicity: Like many alkylating agents, thiotepa has been reported to be carcinogenic when administered to laboratory animals. Carcinogenicity is shown most clearly in studies using mice, but there is some evidence of carcinogenicity in man. There is an increased risk of a secondary malignancy with use of TEPADINA. Inform patients that TEPADINA can increase the risk of secondary malignancy.
• Embryo-Fetal Toxicity: Based on the mechanism of action and findings in animals, TEPADINA can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of TEPADINA in pregnant women. Thiotepa given by the intraperitoneal (IP) route was teratogenic in mice at doses ≥ 1 mg/kg (3.2 mg/m²), approximately 8-fold less than the maximum recommended human therapeutic dose (0.8 mg/kg, 27 mg/m²), based on body-surface area. Thiotepa given by the IP route was teratogenic in rats at doses ≥ 3 mg/kg (21 mg/m²), approximately equal to the maximum recommended human therapeutic dose, based on body-surface area. Thiotepa was lethal to rabbit fetuses at a dose of 3 mg/kg (41 mg/m²), approximately two times the maximum recommended human therapeutic dose based on body-surface area. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use highly effective contraception during and after treatment with TEPADINA for 6 months after therapy. Advise males of reproductive potential to use effective contraception during and after treatment with TEPADINA for 1 year after therapy.

ADVERSE REACTIONS

The most common adverse reactions (incidence greater than 10%) are neutropenia, anemia, thrombocytopenia, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated bilirubin, mucositis, cytomegalovirus infection, hemorrhage, diarrhea, hematuria and rash. The clinically significant adverse reactions include myelosuppression, infection, hypersensitivity, cutaneous toxicity, hepatic veno-occlusive disease, central nervous system toxicity, and carcinogenicity.

DRUG INTERACTIONS

Effect of Cytochrome CYP3A Inhibitors and Inducers: In vitro studies suggest that thiotepa is metabolized by CYP3A4 and CYP2B6 to its active metabolite TEPA. Avoid co-administration of strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (e.g., rifampin, phenytoin) with TEPADINA due to the potential effects on efficacy and toxicity. Consider alternative medications with no or minimal potential to inhibit or induce CYP3A4. If concomitant use of strong CYP3A4 modulators cannot be avoided, closely monitor for adverse drug reactions.

Effect of TEPADINA on Cytochrome CYP2B6 Substrates: In vitro studies suggest that thiotepa inhibits CYP2B6. TEPADINA may increase the exposure of drugs that are substrates of CYP2B6 in patients; however, the clinical relevance of this in vitro interaction is unknown. The administration of thiotepa with cyclophosphamide in patients reduces the conversion of cyclophosphamide to the active metabolite, 4-hydroxycyclophosphamide; the effect appears sequence dependent with a greater reduction in the conversion to 4-hydroxycyclophosphamide when thiotepa is administered 1.5 hours prior to the intravenous administration of cyclophosphamide compared to administration of thiotepa after intravenous cyclophosphamide. The reduction in 4-hydroxycyclophosphamide levels may potentially reduce efficacy of cyclophosphamide treatment.

USE IN SPECIFIC POPULATIONS

Pregnancy: TEPADINA can cause fetal harm when administered to a pregnant woman based on findings from animals and the drug’s mechanism of action. Limited available data with TEPADINA use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage.  In animal reproduction studies, administration of thiotepa to pregnant mice and rats during organogenesis produced teratogenic effects (neural tube defects and malformations of the skeletal system of the fetus) at doses approximately 0.125 and 1 times, respectively, the maximum recommended human daily dose on a mg/m² basis. Thiotepa was lethal to rabbit fetuses at approximately 2 times the maximum recommended human therapeutic dose based on body-surface area.  Consider the benefits and risks of TEPADINA for the mother and possible risks to the fetus when prescribing TEPADINA to a pregnant woman.

Lactation: There is no information regarding the presence of thiotepa in human milk, the effects on the breastfed infant, or the effects on milk production.

Because of the potential for serious adverse reactions, including the potential for tumorigenicity shown for thiotepa in animal studies, advise patients not to breastfeed during TEPADINA treatment.

Females and Males of Reproductive Potential: TEPADINA can cause fetal harm when administered to a pregnant woman.

Pregnancy Testing – Verify the pregnancy status of females of reproductive potential prior to initiating TEPADINA therapy.

Contraception for Females – Advise females of reproductive potential to avoid pregnancy during TEPADINA treatment and for 6 months after the final dose of TEPADINA. Advise females to immediately report pregnancy.

Contraception for Males – TEPADINA may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities. Males with female sexual partners of reproductive potential should use effective contraception during TEPADINA treatment and for 1 year after the final dose of TEPADINA.

Infertility – Based on nonclinical findings, male and female fertility may be compromised by treatment with TEPADINA. Inform male patients about the possibility of sperm conservation before the start of therapy.

Pediatric Use: The safety and effectiveness of TEPADINA for prevention of graft rejection in pediatric patients undergoing allogeneic HSCT for class 3 beta-thalassemia was established in one prospective study and one retrospective study that included 1 infant (1 month to 1 year), 23 children (2 to 11 years) and 13 adolescents (12 to 16 years) who received TEPADINA as part of their preparative regimen. Safety and effectiveness of TEPADINA in neonates have not been established. Safety and effectiveness of TEPADINA for treatment of adenocarcinoma of the breast, adenocarcinoma of the ovary, malignant effusions and superficial papillary carcinoma of the urinary bladder in pediatric patients have not been established.

Geriatric Use: The safety and effectiveness of TEPADINA as a preparative regimen prior to allogeneic hematopoietic progenitor (stem) cell transplantation (HSCT) for patients with class 3 beta-thalassemia have not been established in geriatric patients. Clinical studies of TEPADINA for this indication did not include subjects aged 65 and over. Clinical studies of TEPADINA for treatment of adenocarcinoma of the breast, adenocarcinoma of the ovary, malignant effusions and superficial papillary carcinoma of the urinary bladder did not include sufficient numbers of subjects aged 65 and over to determine whether elderly subjects respond differently from younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreasing hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Renal Impairment: In patients with moderate (creatinine clearance (CLcr) of 30 mL/min to 59 mL/min) renal impairment, decreased renal excretion may result in increased plasma levels of thiotepa and TEPA. This may result in increased toxicity. Monitor patients with moderate to severe (CLcr < 30 mL/min) renal impairment for signs and symptoms of toxicity following treatment with TEPADINA for an extended period of time.

Hepatic Impairment: Thiotepa is extensively metabolized in the liver. Patients with moderate (bilirubin levels greater than 1.5 times to 3 times the upper limit of normal and any AST) hepatic impairment may have increased plasma levels of thiotepa. This may result in toxicity. Monitor patients with moderate to severe (bilirubin levels greater than 3 times upper limit of normal and any AST) hepatic impairment for signs and symptoms of toxicity following treatment with TEPADINA for an extended period of time. HHHHH

To report suspected adverse reactions, contact ADIENENE at 844-668-3940 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please click here for full Prescribing Information.

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TEPWP-02  8-4-25