TEPADINA thiotepa 200 mg Injection, Powder, Lyophilized, For Solution, 1 injection
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Alkylating Drug class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Thiotepa injection is used to treat certain types of ovarian cancer (cancer that begins in the female reproductive organs where eggs are formed), breast, and bladder cancer. It is also used to treat malignant effusions (a condition when fluid collects in the lungs or around the heart) that are caused by cancerous tumors. Thiotepa is in a class of medications called alkylating agents. It works by slowing or stopping the growth of cancer cells in your body.
Read the full MedlinePlus article ↗- Thiotepa is a chemotherapy drug used for a few different conditions. It treats certain breast and ovarian cancers, helps control cancer-related fluid buildup in body cavities, and...
- No, thiotepa is never taken at home. It's always given by a trained healthcare team in a hospital or clinic. Depending on what it's treating, it may be infused into a vein (intrave...
- How will I receive thiotepa — do I take it at home?
- Some side effects are very common — especially low blood counts, which can make you feel tired and more prone to infection. You may also experience mouth sores, nausea, diarrhea, a...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Thiotepa — tap one for details:
Thiotepa may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
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🧪 Inactive Ingredients / Excipients
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200 mL
UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
1 inactive ingredient listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9342 | $4.931 / J9342 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Tepadina 200 mgthis 70121-2749-01 | Amneal | 1 injection | — | AP | FDA listed | — |
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⏳ Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 9931458 ↗ | Drug product | — | May 31, 2037 |
| US 9931458 ↗ | Drug product | — | May 31, 2037 |
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 70121-2749-01 You're viewing this | 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 BOX (70121-2749-1) | 2025-04-18 | Active |
🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: SEVERE MYELOSUPPRESSION and CARCINOGENICITY TEPADINA 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 (HSCT) is required to prevent potentially fatal complications of the prolonged myelosuppression after high doses of TEPADINA [see Warnings and Precautions (5.1) ] TEPADINA should be considered potentially carcinogenic in humans [see Warnings and Precautions (5.7) ] WARNING: SEVERE MYELOSUPPRESSION and CARCINOGENICITY See full prescribing information for complete boxed warning.
May cause severe marrow suppression or ablation with resulting infection or bleeding. Monitor hematologic laboratory parameters. (5.1) Potentially carcinogenic in humans.
(5.7)
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE TEPADINA (thiotepa) is an alkylating drug indicated: 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. (1.1 , 14) For treatment of adenocarcinoma of the breast or ovary. (1.2) For controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities.
(1.3) For treatment of superficial papillary carcinoma of the urinary bladder. (1.4)
1.1Class 3 Beta-Thalassemia TEPADINA is indicated 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 Clinical Studies ( 14 ) ] .
1.2Adenocarcinoma of the Breast or Ovary TEPADINA is indicated for treatment of adenocarcinoma of the breast or ovary.
1.3Malignant Effusions TEPADINA is indicated for controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities.
1.4Superficial Papillary Carcinoma of the Urinary Bladder TEPADINA is indicated for treatment of superficial papillary carcinoma of the urinary bladder.
1.1Class 3 Beta-Thalassemia TEPADINA is indicated 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 Clinical Studies ( 14 ) ] .
1.2Adenocarcinoma of the Breast or Ovary TEPADINA is indicated for treatment of adenocarcinoma of the breast or ovary.
1.3Malignant Effusions TEPADINA is indicated for controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities.
1.4Superficial Papillary Carcinoma of the Urinary Bladder TEPADINA is indicated for treatment of superficial papillary carcinoma of the urinary bladder.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION The recommended dosage of TEPADINA for class 3 beta-thalassemia is two administrations of 5 mg/kg given by intravenous infusion approximately 12 hours apart on Day -6 before allogeneic HSCT in conjunction with high-dose busulfan and cyclophosphamide. (2.1) The recommended dosage of TEPADINA for treatment of adenocarcinoma of the breast or ovary is 0.3 mg/kg to 0.4 mg/kg by intravenous infusion. (2.1) The recommended dosage of TEPADINA for treatment of malignant effusions is 0.6 mg/kg to 0.8 mg/kg intracavitary.
(2.1) The recommended dosage of TEPADINA for treatment of superficial papillary carcinoma of the urinary bladder is 60 mg in 30 mL to 60 mL of 0.9% Sodium Chloride Injection into the bladder by catheter. (2.1) See Full Prescribing Information for preparation and administration instructions. (2.2 , 2.3)
2.1Recommended Dosage Class 3 Beta-Thalassemia The recommended dosage of TEPADINA in pediatric patients is two administrations of 5 mg/kg given by intravenous infusion approximately 12 hours apart on Day -6 before allogeneic HSCT in conjunction with high-dose busulfan and cyclophosphamide as outlined in Table 1. See Prescribing Information for cyclophosphamide and busulfan for information on these drugs. Table 1: Dosage Regimen For Allogeneic HSCT In Pediatric Patients With Class 3 Beta-Thalassemia Treatment Day prior to transplantation Day ‑10 Day ‑9 Day ‑8 Day ‑7 Day ‑6 Day ‑5 Day ‑4 Day ‑3 Day ‑2 Day ‑1 Day 0 Busulfan intravenous weight-based dose * ▲ ▲ ▲ ▲ TEPADINA intravenous 5 mg/kg twice ▲ Cyclophosphamide intravenous 40 mg/kg/day ▲ ▲ ▲ ▲ Stem cell Infusion ▲ *Busulfan intravenous weight-based dose: 1 mg/kg every 6 hours for patients less than 9 kg; 1.2 mg/kg every 6 hours for patients 9 kg to 16 kg; 1.1 mg/kg every 6 hours for patients 16.1 kg to 23 kg; 0.95 mg/kg every 6 hours for patients 23.1 kg to 34 kg; 0.8 mg/kg every 6 hours for patients more than 34 kg.
Infuse TEPADINA via a central venous catheter over 3 hours using an infusion set equipped with a 0.2 micron in-line filter. Prior to and following each infusion, flush the catheter with approximately 5 mL of 0.9% Sodium Chloride Injection. TEPADINA is excreted through the skin of patients receiving high-dose therapy.
Take precautions to prevent skin toxicity [ see Warnings and Precautions ( 5.3 ) ] . Adenocarcinoma of the Breast or Ovary The recommended dosage of TEPADINA for treatment of adenocarcinoma of the breast or ovary is 0.3 mg/kg to 0.4 mg/kg by intravenous infusion. Doses should be given at 1 to 4 week intervals.
Initially the higher dose in the given range is commonly administered. The maintenance dose should be adjusted weekly on the basis of pre-treatment control blood counts and subsequent blood counts. Maintenance dosages should not be administered more frequently than weekly.
Malignant Effusions The recommended dosage of TEPADINA for treatment of malignant effusions is 0.6 mg/kg to 0.8 mg/kg intracavitary. Administration is usually effected through the same tubing which is used to remove the fluid from the cavity involved. Doses should be given at 1 to 4 week intervals.
Initially the higher dose in the given range is commonly administered. The maintenance dose should be adjusted weekly on the basis of pre-treatment control blood counts and subsequent blood counts. Maintenance dosages should not be administered more frequently than weekly.
Superficial Papillary Carcinoma of the Urinary Bladder The recommended dosage of TEPADINA for treatment of superficial papillary carcinoma of the urinary bladder is 60 mg in 30 mL to 60 mL of 0.9% Sodium Chloride Injection into the bladder by catheter. The solution should be retained for 2 hours. If the patient finds it impossible to retain 60 mL for 2 hours, the dose may be given in a volume of 30 mL.
The patient may be repositioned every 15 minutes for maximum area contact. The usual course of treatment is once a week for 4 weeks. The course may be repeated if necessary, but s…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS For injection:15 mg, lyophilized white powder in single-dose vial for reconstitution. For injection:100 mg, lyophilized white powder in single-dose vial for reconstitution. For injection: 200 mg, lyophilized white powder thiotepa and 200 mL 0.9% Sodium Chloride Injection in single-dose multichamber flexible bag for reconstitution.
For injection: 400 mg, lyophilized white powder thiotepa and 400 mL 0.9% Sodium Chloride Injection in single-dose multichamber flexible bag for reconstitution. For injection: 15 mg, lyophilized white powder in single-dose vial for reconstitution. (3) For injection: 100 mg, lyophilized white powder in single-dose vial for reconstitution.
(3) For injection: 200 mg, lyophilized white powder and 200 mL 0.9% Sodium Chloride Injection in single-dose multichamber flexible bag for reconstitution. (3) For injection: 400 mg, lyophilized white powder and 400 mL 0.9% Sodium Chloride Injection in single-dose multichamber flexible bag for reconstitution. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS TEPADINA is contraindicated in: Patients with severe hypersensitivity to thiotepa [ see Warnings and Precautions (5.2) ] Concomitant use with live or attenuated vaccines [ see Warnings and Precautions (5.4) ] Hypersensitivity to the active substance (4) . Concomitant use with live or attenuated vaccines (4) .
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Cutaneous toxicity: Cleanse skin at least twice daily through 48 hours after the last dose of TEPADINA. (5.3) Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus and to use effective contraception. (5.8)
5.1Myelosuppression 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 [ see Adverse Reactions (6.1) ] .
5.2Hypersensitivity 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 [see Contraindications ( 4 ) , Adverse Reactions ( 6.1 ) ] .
5.3Cutaneous 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.
5.4Concomitant 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.
5.5Hepatic Veno-Occlusive Disease Hepatic veno-occlusive disease may occur in patients who have received high-dose TEPADINA in conjunction with busulfan and cyclophosphamide [ see Adverse Reactions (6.1) ]. 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.
5.6Central 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 behaviour 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 centr…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [ see Warnings and Precautions ( 5.1 ) ] Infection [ see Warnings and Precautions ( 5.1 ) ] Hypersensitivity [ see Warnings and Precautions ( 5.2 ) ] Cutaneous Toxicity [ see Warnings and Precautions ( 5.3 ) ] Hepatic Veno-Occlusive Disease [ see Warnings and Precautions ( 5.5 ) ] Central Nervous System Toxicity [ see Warnings and Precautions (5.6) ] Carcinogenicity [ see Warnings and Precautions (5.7) ] 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.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact ADIENNE at 844-668-3940 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions With the Preparative Regimen for Class 3 Beta-Thalassemia The safety of TEPADINA was evaluated by retrospective analysis of 76 pediatric patients with class 3 beta-thalassemia who underwent allogeneic hematopoietic progenitor (stem) cell transplantation (HSCT) using busulfan and cyclophosphamide with TEPADINA (n=25) or without TEPADINA (n=51) [ see Clinical Studies ( 14 ) ] .
Adverse reactions were abstracted retrospectively from the medical records. Serious adverse events that occurred in the TEPADINA-treated and control cohort were, respectively: gastrointestinal hemorrhage (4% vs 2%), pneumonia (4% vs 0), seizure (4% vs 2%), subarachnoid hemorrhage (4% vs 0) and veno-occlusive disease (4% vs 2%). By 90 days after HSCT, grades 2 to 4 acute graft-versus-host disease was observed in 7 (28%) patients in the TEPADINA cohort and in 13 (26%) patients in the control cohort.
By 1-year after transplantation, chronic graft-versus-host disease was observed in 8 (35%) of 23 evaluable patients in the TEPADINA cohort, and 7 (14%) of 49 evaluable patients in the control cohort. Adverse reactions occurring in at least 5% of patients treated with TEPADINA from start of the preparative regimen through 30 days after transplantation are shown in Table 3. Ta ble 3: Common Adverse Reactions (>5%) Occurring Through 30 Days After Transplantation In Patients With Class 3 Beta- Thalassemia Using Busulfan And Cyclophosphamide With Or Without TEPADINA in the Preparative Regimen Preparative Regimen of Busulfan and Cyclophosphamide With TEPADINA N=25 patients (%) Without TEPADINA N=51 patients (%) Adverse Reaction Any Grade Grade 3-5 1 Any Grade Grade 3-5 1 Mucositis 2 16 (64%) 4 (16%) 22 (43%) 1 (2%) Cytomegalovirus Infection 12 (48%) 0 15 (29%) 0 Hemorrhage 3 7 (28%) 2 (8%) 12 (24%) 3 (6%) Diarrhea 6 (24%) 0 7 (14%) 2 (4%) Hematuria 4 5 (20%) 0 10 (20%) 3 (6%) Rash 5 3 (12%) 0 11 (22%) 0 Intracranial Hemorrhage 6 2 (8%) 1 (4%) 0 0 Pseudomonas Infection 2 (8%) 0 0 0 1 Severe, life-threatening or fatal 2 Mucositis includes mouth hemorrhage, mucosal inflammation and stomatitis 3 Hemorrhage includes all hemorrhage terms 4 Hematuria includes cystitis hemorrhagic and hematuria 5 Rash includes dermatitis exfoliative, palmar erythema, rash, rash maculo-papular, rash pruritic and skin toxicity 6 Hemorrhage Intracranial includes hemorrhage intracranial and subarachnoid hemorrhage All patients in the TEPADINA-treated and control cohorts developed profound cytopenias, including neutropenia, anemia, thrombocytopenia.
Table 4 shows the selected chemistry abnormalities that occurred from start of the preparative regimen through 30 days after transplantation. Table 4: Selected Laboratory Abnormalities Occurring Through 30 Days After…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS
7.1Effect 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 [see Clinical Pharmacology ( 12.3 ) ] . 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.
7.2Effect 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 [see Clinical Pharmacology ( 12.3 ) ] . 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 [see Clinical Pharmacology ( 12.3 ) ] .
The reduction in 4-hydroxycyclophosphamide levels may potentially reduce efficacy of cyclophosphamide treatment.
7.1Effect 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 [see Clinical Pharmacology ( 12.3 ) ] . 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.
7.2Effect 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 [see Clinical Pharmacology ( 12.3 ) ] . 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 [see Clinical Pharmacology ( 12.3 ) ] .
The reduction in 4-hydroxycyclophosphamide levels may potentially reduce efficacy of cyclophosphamide treatment.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. (8.2) Moderate or severe renal impairment: Monitor patients more frequently for toxicity. (8.6 , 12.3) Moderate or severe hepatic impairment: Monitor patients more frequently for toxicity. (8.7 , 12.3)
8.1Pregnancy Risk Summary TEPADINA can cause fetal harm when administered to a pregnant woman based on findings from animals and the drug’s mechanism of action [ see Clinical Pharmacology ( 12.1 ) ] . 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/m 2 basis.
Thiotepa was lethal to rabbit fetuses at approximately 2 times the maximum recommended human therapeutic dose based on body-surface area [ see Data]. Consider the benefits and risks of TEPADINA for the mother and possible risks to the fetus when prescribing TEPADINA to a pregnant woman. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Thiotepa given by the IP route in mice at doses ≥ 1 mg/kg (3.2 mg/m 2 ), approximately 8-fold less than the maximum recommended human therapeutic dose based on body-surface area, and in rats at doses ≥ 3 mg/kg (21 mg/m 2 ), approximately equal to the maximum recommended human therapeutic dose based on body-surface area, resulted in various malformations including neural tube defects, omphalocele, renal agenesis, atresia ani, limb and digit defects, cleft palate, micrognathia, other skeletal anomalies in the skull, vertebrae and ribs, and reduced skeletal ossification.
Thiotepa was lethal to rabbit fetuses at a dose of 3 mg/kg (41 mg/m 2 ), approximately 2 times the maximum recommended human therapeutic dose based on body-surface area.
8.2Lactation Risk Summary 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.
8.3Females and Males of Reproductive Potential TEPADINA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy testing Verify the pregnancy status of females of reproductive potential prior to initiating TEPADINA therapy. Contraception 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 [ see Use in Specific Populations (8.1) ] . 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 [ see Nonclinical Toxicology ( 13.1 ) ] .
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 [ see Nonclinical Toxicology (13.1) ].
8.4Pediatric 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 [see Clinical S…
🆘 Overdosage ▾
10 OVERDOSE There is no experience with overdoses of thiotepa. The most important adverse reactions expected in case of overdose are myeloablation and pancytopenia [ see Nonclinical Toxicology (13) ] . There is no known antidote for thiotepa. Monitor the hematological status closely and provide vigorous supportive measures as medically indicated.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Thiotepa is a cytotoxic agent of the polyfunctional type, related chemically and pharmacologically to the nitrogen mustard. The radiomimetic action of thiotepa is believed to occur through the release of ethyleneimine radicals which, like irradiation, disrupt the bonds of DNA. One of the principle bond disruptions is initiated by alkylation of guanine at the N-7 position, which severs the linkage between the purine base and the sugar and liberates alkylated guanines.
12.2Pharmacodynamics The exposure-response relationship for efficacy and safety has not been characterized.
12.3Pharmacokinetics Absorption Thiotepa reached maximal concentrations close to the end infusion following an intravenous infusion. Distribution The binding of thiotepa to plasma proteins is approximately 10% to 20%. The mean volume of distribution (% coefficient of variation) of thiotepa was 30 L/m 2 (44%) or
1.2L/kg (47%) following a single intravenous infusion of TEPADINA at a dose of 5 mg/kg over 3 hours in pediatric population. In adults administered intravenous thiotepa between 20 mg to 250 mg/m 2 as an intravenous bolus or infusion up to 4 hours, the mean volume of distribution of thiotepa ranged from
1.0 L/kg (30%) to
1.9L/kg (17%). Elimination Following a single intravenous infusion over 3 hours of TEPADINA at a dose of 5 mg/kg in pediatric population, the estimated mean (% coefficient of variation) clearance of thiotepa was
0.58 L/hr/kg (60%) or
13.8L/hr/m 2 (52%). The mean terminal elimination half-life was 1.7 hours (64%) for thiotepa and 4 hours (29%) for its major active metabolite, N,N',N''-triethylenephosphoramide (TEPA) in pediatric population. In adults administered intravenous thiotepa between 20 mg to 250 mg/m 2 as an intravenous bolus or infusion up to 4 hours, the mean thiotepa clearance ranged from
14.6 L/hr/m 2 (23%) to
27.9L/hr/m 2 (69%). In adult population, the mean terminal elimination half-life ranged from 1.4 hours (7%) to 3.7 hours (14%) for thiotepa and from 4.9 hours to 17.6 hours (20%) for TEPA. Metabolism Thiotepa undergoes hepatic metabolism.
In vitro data suggests that CYP3A4 and CYP2B6 may be responsible for the metabolism of thiotepa to TEPA, a major active metabolite. Excretion In adult and pediatric patients, urinary excretion of thiotepa accounted for less than 2% of the dose and TEPA accounted for 11% or less of the dose. Specific Populations Hepatic Impairment The clearance of thiotepa following a single TEPADINA dose of 5 mg/kg in pediatric population with mild hepatic impairment was similar to the clearance observed in patients with normal liver function administered thiotepa.
The exposure (as measured by area under the curve (AUC)) of thiotepa increased by 1.6-fold and 1.8-fold following administration of multiple thiotepa doses of 7 mg/kg administered every 2 days with cyclophosphamide in two adult patients who had liver metastases with moderate hepatic impairment compared to the exposure observed in one patient with normal hepatic function . The effect of severe hepatic impairment on thiotepa exposure is unknown. Renal Impairment The exposure (as measured by AUC) of thiotepa increased by 1.4-fold and TEPA increased by 2.6-fold following administration of multiple doses of 120 mg/m 2 /day in one patient with moderate renal impairment (CLcr = 38 mL/min) administered cyclophosphamide plus thiotepa plus carboplatin, compared to exposure of thiotepa in patients with normal renal function.The effects of severe renal impairment or end-stage renal disease on thiotepa exposure are unknown.
Drug Interactions The clinical relevance of in vitro inhibition of the cytochrome P450 enzymes described below is unknown, but it cannot be excluded that the systemic exposure of thiotepa or medicinal products that are substrates for these enzymes may be affected with concomitant administration with TEPADINA. Effect of Cytochrome P450 Modulators on Thiotepa In vitro data demons…
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied TEPADINA (thiotepa) for injection is a lyophilized white powder supplied in a carton containing one single-dose Type I clear glass vial with a rubber stopper (not made with natural rubber latex) or in an aluminum overwrap containing one single-dose multichamber flexible bag as: TEPADINA 15 mg One vial contains 15 mg thiotepa ( NDC 70121-1630-1). TEPADINA 100 mg One vial contains 100 mg thiotepa ( NDC 70121-1631-1 ). TEPADINA 200 mg One multichamber flexible bag contains 200 mg thiotepa and 200 mL 0.9% Sodium Chloride Injection ( NDC 70121-2749-1 ).
TEPADINA 400 mg One multichamber flexible bag contains 400 mg thiotepa and 400 mL 0.9% Sodium Chloride Injection ( NDC 70121-1687-1 ). Storage and Handling TEPADINA multichamber flexible bag and vials must be stored and transported refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze.
Keep the bag in the aluminum overwrap in order to protect it from activation. TEPADINA is a hazardous drug. Follow applicable special handling and disposal procedures.
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📋 Description ▾
11 DESCRIPTION TEPADINA (thiotepa) is an alkylating agent. TEPADINA (thiotepa) for injection is supplied as a non-pyrogenic, sterile lyophilized white powder for intravenous, intracavitary, or intravesical use after reconstitution and dilution. TEPADINA is available In a single-dose vial containing 15 mg thiotepa.
After reconstitution with 1.5 mL of Sterile Water for Injection, each mL contains 10 mg thiotepa; In a single-dose vial containing 100 mg thiotepa. After reconstitution with 10 mL of Sterile Water for Injection, each mL contains 10 mg thiotepa; In a single-dose multichamber flexible bag containing 200 mg thiotepa and 200 mL 0.9% Sodium Chloride Injection; In a single-dose multichamber flexible bag containing 400 mg thiotepa and 400 mL 0.9% Sodium Chloride Injection; Thiotepa is a synthetic product with antitumor activity.
The chemical name for thiotepa is Tris(1-aziridinyl)phosphine sulfide. Thiotepa has the following structural formula: Thiotepa has the molecular formula C 6 H 12 N 3 PS, and a molecular weight of 189.23, and it appears as fine, white crystalline flakes, with a melting range of 52°C to 57°C. It is soluble in water and organic solvents.
When reconstituted with sterile water for injection, the resulting solution has a pH of approximately 5.5 to 7.5. Thiotepa is unstable in acid medium. Thiotepa Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Hypersensitivity Counsel patients on the signs and symptoms of hypersensitivity and to seek immediate emergency assistance if they develop any of these signs and symptoms [see Warnings and Precautions (5.2) ] . Myelosuppression 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 [see Warnings and Precautions (5.1) ] .
Females and Males of Reproductive Potential TEPADINA can cause fetal harm. Advise females receiving TEPADINA to avoid pregnancy during TEPADINA treatment and for 6 months after the last dose of TEPADINA [see Warnings and Precautions (5.8) ] . Advise males with female sexual partners of reproductive potential to use effective contraception during TEPADINA treatment and for 1 year after the last dose of TEPADINA [see Use in Specific Populations (8.3) ] .
Advise females to report pregnancy immediately [see Warnings and Precautions (5.8) ] . Advise patients that TEPADINA can produce infertility. Inform male patients about the possibility of sperm conservation before the start of therapy [see Use in Specific Populations (8.3) ] .
Lactation Advise patients to avoid breastfeeding while receiving TEPADINA [see Use in Specific Populations (8.2) ] . Secondary malignancies Inform patients that TEPADINA can increase the risk of secondary malignancy [see Warnings and Precautions (5.7) ] . Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807 for ADIENNE SA Switzerland U.S.
Pat. No. 9,931,458