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TEPYLUTE thiotepa 10 mg/mL Injection, 1 vial — NDC 81927-0105-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

TEPYLUTE thiotepa 10 mg/mL Injection, 1 vial — NDC 81927-105-01 (Billing 81927-0105-01)

by Shorla Oncology Inc. · 1 VIAL, SINGLE-DOSE in 1 CARTON / 1.5 mL in 1 VIAL, SINGLE-DOSE

This is a package of 1 vial of TEPYLUTE thiotepa 10 mg/mL Injection from Shorla Oncology Inc., no longer marketed (first marketed Mar 2025), no longer in the FDA NDC Directory, this package's marketing ended Sep 2026. It is this product's only package size.

NDC 81927-0105-01
🏷️ FDA NDC (as labeled) 81927-105-01 billing pads the product segment with a zero
Rx only Brand Discontinued Non-controlled ⚠ Discontinued by firm ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Oct 1, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 81927-105-01 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
81927 labeler · 105 product · 01 package
Package marketed since
Mar 31, 2025
Package marketing ended
Sep 30, 2026
Sample package
No — commercial package
Barcode (UPC-A, from the NDC)
3 8192710501 7
FDA record last changed
Oct 1, 2026
⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through Sep 2026. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 81927-105-01
Product NDC 81927-105
11-digit billing NDC 81927010501
NCPDP billing unit ML — per mL (volume)
Application # NDA216984
SPL Set ID add44e98-a042-4e38-b870-beb36693805b
Established class (EPC) Alkylating Drug
Mechanism of action Alkylating Activity
DEA schedule Non-controlled
Marketing category NDA
Marketing status Discontinued
FDA listing status Discontinued by firm (certified through Sep 2026)
Marketing start 2025-03-31
Marketing end 2026-09-30
Route INTRAVENOUS
Dosage form INJECTION
Substance THIOTEPA

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GCN Seq No 086254
GCN 55941
HICL code 003898
Ingredient (HICL) Thiotepa
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1A
Therapeutic class — specific (HIC3) Antineoplastic - Alkylating Agents
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name TEPYLUTE 15 MG/1.5 ML VIAL
FDB brand name Tepylute
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 086254
  • GCN: 55941
  • HICL (First Databank): 003898
  • AHFS class code: 10:00.00.00
Why two NDCs? The FDA registers this code as 81927-105-01 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 81927-0105-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

Clinical

Label name TEPYLUTE 15 MG/1.5 ML VIAL Ingredient Thiotepa
📖 What it is MedlinePlus · NLM

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 ↗
📗 Our plain-language guide HelloPharmacist
  • It is a chemotherapy medicine. Tepadina is used before stem cell transplant in children with class 3 beta-thalassemia. It is also used for breast or ovarian adenocarcinoma, cancer-...
  • A healthcare team gives it to you. Depending on the use, it goes into a vein, into a body cavity, or into your bladder through a catheter. Your team decides the schedule and checks...
  • Low blood counts are very common. You may also get mouth sores, diarrhea, rash, bleeding, blood in the urine, nausea and tiredness. Call right away for fever, signs of infection, u...
  • Thiotepa can leave your body partly through the skin and cause discoloration, itching, blistering or peeling. The label advises bathing at least twice daily through 48 hours after...
📖 Read our full Thiotepa Injection guide →
1
Nutrient depletion considerations

Thiotepa may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Thiotepa nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 systemPer eachPer 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 · J9341 $36.640 / J9341 unit —
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Billing & reimbursement

FDA NDC (as labeled)81927-105-01
11-digit billing NDC81927-0105-01
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ9341
DescriptorINJECTION, THIOTEPA (TEPYLUTE), 1 MG
Billing units / pkg10 units
How the units are derivedThis package is 1.5 ML; the HCPCS unit is 1 MG, so one package = 10 billing units.
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
81927-0105-01 You're viewing this Main listing 1 VIAL, SINGLE-DOSE in 1 CARTON / 1.5 mL in 1 VIAL, SINGLE-DOSE 2025-03-31 Sep 30, 2026 Discontinued by firm

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Tepylute 10 mg/mLthis 81927-0105-01 Shorla 1 vial — — Discontinued —
Tepylute 10 mg/mL 81927-0106-01 Shorla 1 vial — — Discontinued —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2024
First FDA approval
Jun 2024
📍
2026
Currently FDA-listed
2 years listed
🛡️
2041
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Aug 2041. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Jun 25, 2024 RLD RS ⏳ ~14.9 yr to latest listed protection

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.

Patents & exclusivity — FDA Orange Book
US 12622921 — method of use (U-4530)
US 12622921 — method of use (U-4530)
US 11975013 — drug product
US 11975013 — drug product
2024 2026 2028 2030 2032 2034 2036 2038 2040
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 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.

Listed patents (4)
PatentTypeUse codeExpires
US 12622921 ↗ Method of use U-4530 Aug 16, 2041
US 12622921 ↗ Method of use U-4530 Aug 16, 2041
US 11975013 ↗ Drug product — Aug 16, 2041
US 11975013 ↗ Drug product — Aug 16, 2041
Common questions
Is there a generic version of TEPYLUTE 15 MG/1.5 ML VIAL?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for TEPYLUTE 15 MG/1.5 ML VIAL. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Aug 2041 — an estimate, not a guaranteed launch date.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

🧪 Avoiding an ingredient? See Thiotepa Injection inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerShorla Oncology Inc.
Application holderSHORLA PHARMA LTD
FDA applicationNDA216984 (NDA)
Labeler code81927
First marketedMar 2025
Product typeHuman Prescription Drug
Portfolio5 products on file

More NDCs from Shorla Oncology Inc. labeler code 81927

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 88 words ▾

WARNING: SEVERE MYELOSUPPRESSION and CARCINOGENICITY TEPYLUTE may cause severe marrow suppression, and high doses may cause marrow ablation with resulting infection or bleeding. Monitor hematologic laboratory parameters. [see Warnings and Precautions ( 5.1 )]. TEPYLUTE 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 41 words ▾

1 INDICATIONS AND USAGE TEPYLUTE is an alkylating drug indicated for treatment of adenocarcinoma of the breast or ovary. ( 1.1 )

1.1Adenocarcinoma of the Breast or Ovary TEPYLUTE is indicated for treatment of adenocarcinoma of the breast or ovary.

⏱️ Dosage and Administration ~1 min read ▾

2 DOSAGE AND ADMINISTRATION The recommended dose of TEPYLUTE for treatment of adenocarcinoma of the breast or ovary is 0.3 mg/kg to 0.4 mg/kg intravenously. ( 2.1 ) See full prescribing information for preparation instructions. ( 2.2 )

2.1Recommended Dosage Adenocarcinoma of the Breast or Ovary The recommended dose of TEPYLUTE for treatment of adenocarcinoma of the breast or ovary is 0.3 mg/kg to 0.4 mg/kg intravenously. 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 pretreatment control blood counts and subsequent blood counts. Maintenance doses should not be administered more frequently than weekly.

2.2Preparation Instructions TEPYLUTE is a hazardous drug. Follow applicable special handling and disposal procedures 1 . Use aseptic technique to prepare TEPYLUTE.

Dilution in the infusion bag Remove vial from refrigerated conditions 1 hour prior to dilution. Dilute the solution in an appropriate volume of 0.9% Sodium Chloride Injection to obtain a final TEPYLUTE concentration between 0.5 mg/mL and 1 mg/mL. Use a 16G needle with a Luer-lock syringe to dilute the solution.

Use the diluted TEPYLUTE infusion solution immediately. If the solution is not used immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours, or at room temperature 25°C (77°F) for up to 4 hours. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Use TEPYLUTE diluted solutions only if free of visible particulate matter. Filter using a 0.2 micron filter prior to administration. Filtering does not alter solution potency.

Storage of Undiluted TEPYLUTE: Single-dose vial: Each vial is intended for single-dose only. Discard any unused portion left in the vial. Multiple-dose vial: After first use, store the partially used vial in the original carton refrigerated at 2°C to 8°C (36°F to 46°F) for up to 28 days.

💊 Dosage Forms and Strengths 73 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 15 mg/1.5 mL (10 mg/mL) of thiotepa in a clear, colorless or almost colorless solution in single-dose vial. Injection: 100 mg/10 mL (10 mg/mL) of thiotepa in a clear, colorless or almost colorless solution in multiple-dose vial. Injection: 15 mg/1.5 mL (10 mg/mL) of thiotepa solution in single-dose vial. ( 3 ) Injection: 100 mg/10 mL (10 mg/mL) of thiotepa solution in multiple-dose vial ( 3 ).

⛔ Contraindications 51 words ▾

4 CONTRAINDICATIONS TEPYLUTE 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 ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Cutaneous Toxicity: Cleanse skin at least twice daily through 48 hours after the last dose of TEPYLUTE. ( 5.3 ) Polyethylene Glycol 400 Toxicity: Take into consideration the PEG 400 load from concomitant medications. ( 5.8 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.9 )

5.1Myelosuppression For patients receiving TEPYLUTE for treatment of adenocarcinoma of the breast or adenocarcinoma of the ovary, if the bone marrow has been compromised by prior irradiation or chemotherapy, or is recovering from chemotherapy, the risk of severe myelosuppression with TEPYLUTE may be increased. Perform periodic complete blood counts during the course of treatment with TEPYLUTE. 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 thiotepa. If anaphylactic or other clinically significant allergic reaction occurs, discontinue treatment with TEPYLUTE, initiate appropriate therapy, and monitor until signs and symptoms resolve [see Contraindications ( 4 ) and Adverse Reactions ( 6.1 )] .

5.3Cutaneous Toxicity TEPYLUTE and/or its active metabolites may be excreted in part via skin in patients receiving high-dose therapy. Treatment with TEPYLUTE 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 TEPYLUTE.

Change occlusive dressing and clean the covered skin at least twice daily through 48 hours after administration of TEPYLUTE. Change bed sheets daily during treatment. Skin reactions associated with accidental exposure to TEPYLUTE may occur.

Wash the skin thoroughly with soap and water in case TEPYLUTE solution contacts the skin. Flush mucous membranes in case of TEPYLUTE 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 TEPYLUTE until the immunosuppressive effects have resolved.

5.5Hepatic Veno-Occlusive Disease Monitor by physical examination, serum transaminases and bilirubin, 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 behavior and forgetfulness have been reported to occur in a dose-dependent manner during or shortly after administration of high-dose thiotepa. Do not exceed the recommended dose of TEPYLUTE.

If severe or life-threatening central nervous system toxicity occurs, discontinue administration of TEPYLUTE and provide supportive care.

5.7Carcinogenicity Like many alkylating agents, thiotepa has been reported to be carcinogenic when administered to laboratory animals [see Nonclinical Toxicity ( 13.1) ] . 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 TEPYLUTE.

5.8Polyethylene Glycol 400 Toxicity TEPYLUTE contains a high concentration of polyethylene glycol (PEG) 400. Based on findings in animals, administration of high amounts of PEG 400 may cause damage to the kidneys and liver at dosages higher than recommended. When prescribing TEPYLUTE, take into consideration the PEG 400 load from concomitant medications.

5.9Embryo-Fetal Toxicity Based on the mechanism of action and fin… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in other sections of the label: 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 Shorla Oncology at 844-9-SHORLA 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions with Treatment of adenocarcinoma of the breast and adenocarcinoma of the ovary Gastrointestinal: Nausea, vomiting, abdominal pain, anorexia. General: Fatigue, weakness.

Febrile reaction and discharge from a subcutaneous lesion may occur as the result of breakdown of tumor tissue. Hypersensitivity Reactions: Allergic reactions - rash, urticaria, laryngeal edema, asthma, anaphylactic shock, wheezing. Local Reactions: Contact dermatitis, pain at the injection site.

Neurologic: Dizziness, headache, blurred vision. Renal: Dysuria, urinary retention, chemical cystitis or hemorrhagic cystitis. Reproductive: Amenorrhea, interference with spermatogenesis.

Respiratory: Prolonged apnea has been reported when succinylcholine was administered prior to surgery, following combined use of thiotepa and other anticancer agents. It was theorized that this was caused by decrease of pseudocholinesterase activity caused by the anticancer drugs. Skin: Dermatitis, alopecia.

Skin depigmentation has been reported following topical use. Special Senses: Conjunctivitis.

6.2Postmarketing Experience The following adverse reactions have been identified during post approval use of thiotepa. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders: Febrile bone marrow aplasia.

Cardiac disorders: Bradycardia, cardiac failure congestive, cardio-respiratory arrest, pericardial effusion, pericarditis, right ventricular hypertrophy. Congenital, familial and genetic disorders: Aplasia. Ear and labyrinth disorders: Deafness.

Eye disorders: Blindness, eyelid ptosis, papilledema, strabismus. Gastrointestinal disorders: Ascites, dysphagia, enterocolitis, gastritis, palatal disorder. General disorders and administration site conditions: Device related infection, gait disturbance, malaise, multi-organ failure, pain.

Hepatobiliary disorders: Hepatomegaly. Immune system disorders: Bone marrow transplant rejection, immunosuppression. Infections and infestations: Acute sinusitis, bronchopulmonary aspergillosis, candida sepsis, enterococcal infection, Epstein-Barr virus infection, Escherichia sepsis, Fusarium infection, gastroenteritis, infection, lower respiratory tract infection fungal, lower respiratory tract infection viral, parainfluenza virus infection, Pneumonia legionella, relapsing fever, respiratory tract infection, sepsis, septic shock, Staphylococcal bacteremia, Staphylococcal infection, systemic candida, urinary tract infection.

Injury, poisoning and procedural complications: Refractoriness to platelet transfusion, sub… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 211 words ▾

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 coadministration of strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (e.g., rifampin, phenytoin) with thiotepa 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 TEPYLUTE on Cytochrome CYP2B6 Substrates In vitro studies suggest that thiotepa inhibits CYP2B6. Thiotepa 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 ~3 min read ▾

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 TEPYLUTE 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 thiotepa 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 TEPYLUTE for the mother and possible risks to the fetus when prescribing TEPYLUTE 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 TEPYLUTE treatment and for 1 week after the last dose.

8.3Females and Males of Reproductive Potential TEPYLUTE 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 TEPYLUTE therapy. Contraception Females Advise females of reproductive potential to avoid pregnancy during TEPYLUTE treatment and for 6 months after the last dose of TEPYLUTE.

Advise females to immediately report pregnancy [see Use in Specific Populations ( 8.1 )]. Males TEPYLUTE may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities. Males with female sexual partners of reproductive potential should use effective contraception during TEPYLUTE treatment and for 1 year after the last dose of TEPYLUTE [see Nonclinical Toxicology ( 13.1 )].

Infertility Based on nonclinical findings, male and female fertility may be compromised by treatment with TEPYLUTE. Inform male patients about the possibility of sperm conservation before the start of therapy [see Nonclinical Toxicology ( 13.1 )].

8.4Pediatric Use Safety and effectiveness of TEPYLUTE in neonates have not been established. Safety and effectiveness of TEPYLUTE for treatment of adenocarcinoma of the breast and adenocarcinoma of the ovary in pediatric… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary TEPYLUTE 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 thiotepa 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 TEPYLUTE for the mother and possible risks to the fetus when prescribing TEPYLUTE 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.

🧒 Pediatric Use 38 words ▾

8.4Pediatric Use Safety and effectiveness of TEPYLUTE in neonates have not been established. Safety and effectiveness of TEPYLUTE for treatment of adenocarcinoma of the breast and adenocarcinoma of the ovary in pediatric patients have not been established.

🧓 Geriatric Use 97 words ▾

8.5Geriatric Use Clinical studies of thiotepa for treatment of adenocarcinoma of the breast and adenocarcinoma of the ovary 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.

🆘 Overdosage 51 words ▾

10 OVERDOSAGE 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 ( 13.1 )] . There is no known antidote for thiotepa. Monitor the hematological status closely and provide vigorous supportive measures as medically indicated.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Thiotepa is an alkylating drug 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.

12.3Pharmacokinetics Absorption Thiotepa reached maximal concentrations close to the end of infusion following an intravenous infusion. Distribution The binding of thiotepa to plasma proteins is approximately 10% to 20%. 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 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 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 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 TEPYLUTE. Effect of Cytochrome P450 Modulators on Thiotepa In vitro data demonstrates that CYP3A4 and CYP2B6 inhibitors decrease the metabolism of thiotepa [see Drug Interactions ( 7.1 )] . Effect of Thiotepa on Cytochrome P450 2B6 In vitro data demonstrates that thiotepa inhibits CYP2B6.

Effect of Thiotepa on Cyclophosphamide The administration of thiotepa 1.5 hours prior to intravenous cyclophosphamide in patients administered cyclophosphamide plus thiotepa plus carboplatin decreased the AUC of 4-hydroxycyclophosphamide by 26% and maximal concentrations of 4-hydroxycyclophosphamide by 62%, compared to administration of cyclophosphamide prior to thiotepa.

🧬 Mechanism of Action 75 words ▾

12.1Mechanism of Action Thiotepa is an alkylating drug 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.

📦 How Supplied / Storage and Handling 152 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied TEPYLUTE injection is supplied as a clear, colorless or almost colorless solution. The vial stopper is not made with natural rubber latex. TEPYLUTE Injection NDC Number Strength Vial Presentation 81927-105-01 15 mg/ 1.5 mL (10 mg/mL) Single-dose vial, carton of 1 81927-106-01 100 mg/ 10 mL (10 mg/mL) Multiple-dose vial, carton of 1 Storage and Handling TEPYLUTE injection vials must be stored and transported refrigerated at 2°C to 8°C (36°F to 46°F).

Do not freeze. TEPYLUTE injection is a hazardous drug. Follow applicable special handling and disposal procedures 1 .

How Supplied TEPYLUTE injection is supplied as a clear, colorless or almost colorless solution. The vial stopper is not made with natural rubber latex. TEPYLUTE Injection NDC Number Strength Vial Presentation 81927-105-01 15 mg/ 1.5 mL (10 mg/mL) Single-dose vial, carton of 1 81927-106-01 100 mg/ 10 mL (10 mg/mL) Multiple-dose vial, carton of 1

📦 Storage and Handling 37 words ▾

Storage and Handling TEPYLUTE injection vials must be stored and transported refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. TEPYLUTE injection is a hazardous drug. Follow applicable special handling and disposal procedures 1 .

📋 Description 145 words ▾

11 DESCRIPTION TEPYLUTE injection contains thiotepa, an alkylating drug. 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. Thiotepa is unstable in acid medium. TEPYLUTE (thiotepa) injection is supplied as a sterile solution for intravenous use after dilution.

When diluted in water, the resulting solution has a pH of approximately 5.5 to 7.5. TEPYLUTE injection is a 10 mg/mL solution available as: 15 mg/1.5 mL strength single-dose vial contains 15 mg thiotepa and 1.7 g of polyethylene glycol 400 100 mg/10 mL strength multiple-dose vial contains 100 mg thiotepa and 11.3 g of polyethylene glycol 400 structural formula

💬 Information for Patients ~1 min read ▾

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 )] .

Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant. Advise females of reproductive potential to use effective contraception during treatment with TEPYLUTE and for 6 months after the last dose [see Warnings and Precautions ( 5.7 ), Use in Specific Populations ( 8.1 , 8.3 )] .

Advise males with female partners of reproductive potential to use effective contraception during TEPYLUTE treatment and for 1 year after the last dose of TEPYLUTE [see Use in Specific Populations ( 8.3 )] . Advise patients that TEPYLUTE 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 women not to breastfeed while receiving TEPYLUTE and for 1 week after the last dose [see Use in Specific Populations ( 8.2 )] . Secondary malignancies Inform patients that TEPYLUTE can increase the risk of secondary malignancy [see Warnings and Precautions ( 5.5 )] . Manufactured by: AqVida GmbH, Dassow, Germany Distributed by: Shorla Oncology Inc., Cambridge, MA 02142, USA Patent Information: U.S.

Patent: 11,975,013 Version: THTGIUS008

🧬 Pharmacokinetics ~2 min read ▾

12.3Pharmacokinetics Absorption Thiotepa reached maximal concentrations close to the end of infusion following an intravenous infusion. Distribution The binding of thiotepa to plasma proteins is approximately 10% to 20%. 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 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 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 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 TEPYLUTE. Effect of Cytochrome P450 Modulators on Thiotepa In vitro data demonstrates that CYP3A4 and CYP2B6 inhibitors decrease the metabolism of thiotepa [see Drug Interactions ( 7.1 )] . Effect of Thiotepa on Cytochrome P450 2B6 In vitro data demonstrates that thiotepa inhibits CYP2B6.

Effect of Thiotepa on Cyclophosphamide The administration of thiotepa 1.5 hours prior to intravenous cyclophosphamide in patients administered cyclophosphamide plus thiotepa plus carboplatin decreased the AUC of 4-hydroxycyclophosphamide by 26% and maximal concentrations of 4-hydroxycyclophosphamide by 62%, compared to administration of cyclophosphamide prior to thiotepa.

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility In mice, repeated intraperitoneal (IP) administration of thiotepa (1.15 or 2.3 mg/kg three times per week for 52 or 43 weeks, respectively) produced a significant increase in the combined incidence of squamous-cell carcinomas of the skin, preputial gland, and ear canal, and combined incidence of lymphoma and lymphocytic leukemia. In other studies in mice, repeated IP administration of thiotepa (4 or 8 mg/kg three times per week for 4 weeks followed by a 20 week observation period or 1.8 mg/kg three times per week for 4 weeks followed by a 35 week observation period) resulted in an increased incidence of lung tumors.

In rats, repeated IP administration of thiotepa (0.7 or 1.4 mg/kg three times per week for 52 or 34 weeks, respectively) produced significant increases in the incidence of squamous-cell carcinomas of the skin or ear canal, combined hematopoietic neoplasms, and uterine adenocarcinomas. Thiotepa given intravenously (IV) to rats (1 mg/kg once per week for 52 weeks) produced an increased incidence of malignant tumors (abdominal cavity sarcoma, lymphosarcoma myelosis, seminoma, fibrosarcoma, salivary gland hemangioendothelioma, mammary sarcoma, pheochromocytoma) and benign tumors.

The lowest reported carcinogenic dose in mice (1.15 mg/kg, 3.68 mg/m 2 ) is approximately 7-fold less than the maximum recommended human therapeutic dose based on body-surface area. The lowest reported carcinogenic dose in rats (0.7 mg/kg, 4.9 mg/m 2 ) is approximately 6-fold less than the maximum recommended human therapeutic dose based on body-surface area. Thiotepa was mutagenic in in vitro assays in Salmonella typhimurium , E coli , Chinese hamster lung and human lymphocytes.

Chromosomal aberrations and sister chromatid exchanges were observed in vitro with thiotepa in bean root tips, human lymphocytes, Chinese hamster lung, and monkey lymphocytes. Mutations were observed with oral thiotepa in mouse at doses > 2.5 mg/kg (8 mg/m 2 ). The mouse micronucleus test was positive with intraperitoneal administration of > 1 mg/kg (3.2 mg/m 2 ).

Other positive in vivo chromosomal aberration or mutation assays included Drosophila melanogaster , Chinese hamster marrow, murine marrow, monkey lymphocyte, and murine germ cell. Thiotepa impaired fertility in male mice at oral or intraperitoneal doses ≥ 0.7 mg/kg (2.24 mg/m 2 ), approximately 12-fold less than the maximum recommended human therapeutic dose based on body-surface area. Thiotepa (0.5 mg) inhibited implantation in female rats when instilled into the uterine cavity.

Thiotepa interfered with spermatogenesis in mice at IP doses ≥ 0.5 mg/kg (1.6 mg/m 2 ), approximately 17-fold less than the maximum recommended human therapeutic dose based on body-surface area. Thiotepa interfered with spermatogenesis in hamsters at an IP dose of 1 mg/kg (4.1 mg/m 2 ), approximately 7-fold less than the maximum recommended human therapeutic dose based on body-surface area.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~2 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility In mice, repeated intraperitoneal (IP) administration of thiotepa (1.15 or 2.3 mg/kg three times per week for 52 or 43 weeks, respectively) produced a significant increase in the combined incidence of squamous-cell carcinomas of the skin, preputial gland, and ear canal, and combined incidence of lymphoma and lymphocytic leukemia. In other studies in mice, repeated IP administration of thiotepa (4 or 8 mg/kg three times per week for 4 weeks followed by a 20 week observation period or 1.8 mg/kg three times per week for 4 weeks followed by a 35 week observation period) resulted in an increased incidence of lung tumors.

In rats, repeated IP administration of thiotepa (0.7 or 1.4 mg/kg three times per week for 52 or 34 weeks, respectively) produced significant increases in the incidence of squamous-cell carcinomas of the skin or ear canal, combined hematopoietic neoplasms, and uterine adenocarcinomas. Thiotepa given intravenously (IV) to rats (1 mg/kg once per week for 52 weeks) produced an increased incidence of malignant tumors (abdominal cavity sarcoma, lymphosarcoma myelosis, seminoma, fibrosarcoma, salivary gland hemangioendothelioma, mammary sarcoma, pheochromocytoma) and benign tumors.

The lowest reported carcinogenic dose in mice (1.15 mg/kg, 3.68 mg/m 2 ) is approximately 7-fold less than the maximum recommended human therapeutic dose based on body-surface area. The lowest reported carcinogenic dose in rats (0.7 mg/kg, 4.9 mg/m 2 ) is approximately 6-fold less than the maximum recommended human therapeutic dose based on body-surface area. Thiotepa was mutagenic in in vitro assays in Salmonella typhimurium , E coli , Chinese hamster lung and human lymphocytes.

Chromosomal aberrations and sister chromatid exchanges were observed in vitro with thiotepa in bean root tips, human lymphocytes, Chinese hamster lung, and monkey lymphocytes. Mutations were observed with oral thiotepa in mouse at doses > 2.5 mg/kg (8 mg/m 2 ). The mouse micronucleus test was positive with intraperitoneal administration of > 1 mg/kg (3.2 mg/m 2 ).

Other positive in vivo chromosomal aberration or mutation assays included Drosophila melanogaster , Chinese hamster marrow, murine marrow, monkey lymphocyte, and murine germ cell. Thiotepa impaired fertility in male mice at oral or intraperitoneal doses ≥ 0.7 mg/kg (2.24 mg/m 2 ), approximately 12-fold less than the maximum recommended human therapeutic dose based on body-surface area. Thiotepa (0.5 mg) inhibited implantation in female rats when instilled into the uterine cavity.

Thiotepa interfered with spermatogenesis in mice at IP doses ≥ 0.5 mg/kg (1.6 mg/m 2 ), approximately 17-fold less than the maximum recommended human therapeutic dose based on body-surface area. Thiotepa interfered with spermatogenesis in hamsters at an IP dose of 1 mg/kg (4.1 mg/m 2 ), approximately 7-fold less than the maximum recommended human therapeutic dose based on body-surface area.

📚 References 11 words ▾

15 REFERENCES 1. OSHA Hazardous Drugs. OSHA. [Accessed from http://www.osha.gov/SLTC/hazardousdrugs/index.html] .

📄 Recent Major Changes 7 words ▾

Dosage and Administration ( 2.2 ) 7/2025

📄 Package Label / Principal Display Panel 162 words ▾

Principal Display Panel - 15 mg/1.5 mL Vial Label NDC 81927-105-01 Rx Only Tepylute ® (thiotepa) injection 15 mg/1.5 mL (10 mg/mL) For intravenous infusion. MUST BE DILUTED PRIOR TO USE. Single-dose vial Discard unused portion 15 mg Vial Label

Principal Display Panel - 15 mg/1.5 mL Carton NDC 81927-105-01 Rx Only Tepylute ® (thiotepa) injection 15 mg/1.5 mL (10 mg/mL) For Intravenous Infusion. MUST BE DILUTED PRIOR TO USE. WARNING: Hazardous Drug Contains one single-dose vial Discard unused portion Sterile 15 mg Carton

Principal Display Panel - 100 mg/10 mL Vial Label NDC 81927-106-01 Rx Only Tepylute ® (thiotepa) injection 100 mg/10 mL (10 mg/mL) For intravenous infusion. MUST BE DILUTED PRIOR TO USE. Multiple-Dose vial 100 mg Vial Label

Principal Display Panel - 100 mg/10 mL Carton NDC 81927-106-01 Rx Only Tepylute ® (thiotepa) injection 100 mg/10 mL (10 mg/mL) For Intravenous Infusion. MUST BE DILUTED PRIOR TO USE. WARNING: Hazardous Drug Contains one Multiple-Dose vial Sterile 100 mg Carton

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Thiotepa — the ingredient across all brands.

Top reported reactions

Febrile Neutropenia814
Mucosal Inflammation807
Cytomegalovirus Infection533
Pyrexia516
Acute Graft Versus Host Disease458
Acute Graft Versus Host Disease In Skin448
Cytomegalovirus Infection Reactivation424

Age at onset

Neonate117
Infant247
Child804
Adolescent262
Adult1,316
Elderly104

Reporter sex

9,494 reports
Male · 54%
Female · 44%
Unknown · 2%

Serious outcomes

Death2,672
Hospitalization1,813
Life-threatening845
Disabling80
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 997 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product No longer marketed (per FDA listing data)
What data is (and isn’t) available for this NDC — tap to expand
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) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is 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.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Who lists this product with the FDA?
Shorla Oncology Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J9341 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 81923-0369-00 · SKINS 81927-0106-01 · Shorla →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.