TIVDAK tisotumab vedotin 40 mg/4mL Injection, Powder, For Solution
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Other monoclonal antibodies and antibody drug conjugates class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Tisotumab vedotin-tftv injection is used to treat cervical cancer (cancer that begins in the opening of the uterus [womb]) that has not improved or has come back after treatment with other medications or has spread to other parts of the body. Tisotumab vedotin-tftv is in a class of medications called antibody-drug conjugates. It works by killing cancer cells.
Read the full MedlinePlus article ↗Patient education
Supplement & herbal interactions
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 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.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII 4QD397987E
An amino acid used as a buffer and stabilizer in medications. It helps maintain the pH balance and protects the active drug from breaking down during storage and use.
-
UNII X573657P6P
Histidine monohydrochloride monohydrate is an amino acid salt used as a buffer in medicines. It helps maintain the proper acidity level of liquid formulations to keep the drug stable and effective.
-
UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
-
UNII C151H8M554
A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
4 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
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
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 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 | $6,971.28 | $27,885.13 / 4 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9273 | $196.121 / J9273 unit | — |
Where does this data come from?
🧾 Billing & reimbursement
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Tivdak 40 mg/4mLthis 51144-0003-01 | SEAGEN | 1 vial | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Sep 20, 2033 |
Is there a biosimilar for TIVDAK 40 MG VIAL?
Why do different websites show different biosimilar dates?
Can a biosimilar launch before the last patent expires?
What does “current Purple Book estimate” mean?
What does “FDA listed” mean?
What does a patent or protection date mean here?
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 51144-0003-01 You're viewing this | 1 VIAL in 1 CARTON (51144-003-01) / 4 mL in 1 VIAL | 2021-09-20 | Active |
🧭 About this NDC listing & data coverage
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) | ✓ 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) | ✓ Available |
Questions about this listing
Why is there no price listed?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Is this package still being marketed?
Who lists this product with the FDA?
Do I need a prescription for this product?
Does this product have a billing J-code?
Where does this data come from?
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: OCULAR TOXICITY • TIVDAK can cause severe ocular toxicities resulting in changes in vision, including severe vision loss, and corneal ulceration. [see Warnings and Precautions (5.1) ]. • Conduct an ophthalmic exam, including an assessment of ocular symptoms, visual acuity, and slit lamp exam of the anterior segment of the eye prior to initiation of TIVDAK, prior to every cycle for the first nine cycles, and as clinically indicated. [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ] . • Adhere to the required premedication and eye care before, during, and after infusion. [see Dosage and Administration (2.2) ]. • Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) ].
WARNING: OCULAR TOXICITY See full prescribing information for complete boxed warning. • TIVDAK can cause severe ocular toxicities resulting in changes in vision, including severe vision loss and corneal ulceration. ( 5.1 ) • Conduct an ophthalmic exam, including an assessment of ocular symptoms, visual acuity, and slit lamp exam of the anterior segment of the eye prior to initiation of TIVDAK, prior to every cycle for the first nine cycles, and as clinically indicated. ( 2.2 , 5.1 ) • Adhere to the required premedication and eye care before, during, and after infusion.
( 2.2 ) • Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity. ( 2.3 , 5.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE TIVDAK ® is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. TIVDAK is a tissue factor-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • For intravenous infusion only. Do not administer TIVDAK as an intravenous push or bolus. Do not mix with, or administer as an infusion with, other medicinal products. ( 2.4 ) • The recommended dose of TIVDAK is 2 mg/kg (up to a maximum of 200 mg) given as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. ( 2.1 )
2.1Recommended Dosage The recommended dose of TIVDAK is 2 mg/kg (up to a maximum of 200 mg for patients ≥100 kg) administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.
2.2Premedication and Required Eye Care Adhere to the following recommendations to reduce the risk of ocular adverse reactions [see Warnings and Precautions (5.1) ]. • Ophthalmic exam by eye care provider: Conduct an ophthalmic exam prior to initiation of TIVDAK, prior to every cycle for the first nine cycles, and as clinically indicated. The ophthalmic exam should include visual acuity, slit lamp exam of the anterior segment of the eye, and an assessment of normal eye movement. • Topical corticosteroid eye drops: Instruct patients to administer one drop in each eye prior to each infusion and to continue to administer eye drops in each eye three times daily for 72 hours after each infusion.
The initial prescription and all renewals of any corticosteroid medication should be made only after examination with a slit lamp. • Topical ocular vasoconstrictor drops: Administer in each eye immediately prior to each infusion of TIVDAK. • Cold packs: Use cooling eye pads during each infusion of TIVDAK. • Topical lubricating eye drops: Instruct patients to administer for the duration of therapy and for 30 days after the last dose of TIVDAK. • Contact lenses: Advise patients to avoid wearing contact lenses for the entire duration of therapy unless advised by their eye care provider.
2.3Dosage Modifications for Adverse Reactions The recommended TIVDAK dose reduction schedule is provided in Table 1 . Table 1: Dosage Reduction Schedule TIVDAK Dose Level Starting dose 2 mg/kg (up to a maximum of 200 mg for patients ≥100 kg) First dose reduction 1.3 mg/kg (up to a maximum of 130 mg for patients ≥100 kg) Second dose reduction 0.9 mg/kg Permanently discontinue in patients who cannot tolerate 0.9 mg/kg (up to a maximum of 90 mg for patients ≥100 kg) The recommended dose modifications for adverse reactions are provided in Table 2 .
Table 2: Dosage Modifications for Adverse Reactions Adverse Reaction Severity Occurrence TIVDAK Dose Modification Keratitis Refer patients to an eye care provider promptly for an assessment of new or worsening ocular symptoms. [see Warnings and Precautions (5.1) ] Nonconfluent superficial keratitis Any Monitor. Confluent superficial keratitis, a corneal epithelial defect, or a 3 line or more loss in best corrected visual acuity First occurrence Withhold dose until resolution, or improvement to nonconfluent superficial keratitis, then resume treatment at the next lower dose level.
Second occurrence Permanently discontinue. Ulcerative keratitis or perforation Any Permanently discontinue. Conjunctival or corneal scarring or symblepharon [see Warnings and Precautions (5.1) ] Any scarring or symblepharon Any Permanently discontinue.
Conjunctivitis and other ocular adverse reactions [see Warnings and Precautions (5.1) ] Nonconfluent superficial punctate conjunctival defects, mild vasodilation Any Monitor. Confluent superficial punctate conjunctival defects, moderate to severe vasodilation First occurrence Withhold dose until resolution or improvement to nonconfluent superficial punctate conjunctival defects, mild vasodilation, then resume treatment at the same dose. Second occurrence Withhold dose until resolution or improvement to nonconfluent superficial punctate conjunctival defects, mild vasodilation, then resume treatment at the next lower dose level.
If no resolution or improvement to nonconfluen…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS For Injection: 40 mg of tisotumab vedotin-tftv as a white to off-white lyophilized cake or powder in a single-dose vial for reconstitution. For Injection: 40 mg as a lyophilized cake or powder in a single-dose vial for reconstitution. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Peripheral neuropathy: Monitor patients for new or worsening peripheral neuropathy. Withhold, reduce the dose, or permanently discontinue TIVDAK based on severity. ( 2.3 , 5.2 ) • Hemorrhage: Monitor patients for signs and symptoms of hemorrhage.
Withhold, reduce the dose, or permanently discontinue TIVDAK based on severity. ( 2.3 , 5.3 ) • Pneumonitis: Severe, life-threatening, or fatal pneumonitis may occur. Withhold TIVDAK for persistent or recurrent Grade 2 pneumonitis and consider dose reduction.
Permanently discontinue TIVDAK for Grade 3 or 4 pneumonitis. ( 2.3 , 5.4 ) • Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions, including events of fatal or life-threatening Stevens-Johnson syndrome (SJS), can occur in patients treated with TIVDAK. Immediately withhold TIVDAK for suspected severe cutaneous adverse reactions, including SJS.
Permanently discontinue TIVDAK for confirmed Grade 3 or 4 severe cutaneous adverse reactions, including SJS. ( 2.3 , 5.5 ) • Embryo-fetal toxicity: TIVDAK can cause fetal harm. Advise of the potential risk to a fetus and to use effective contraception.
( 5.6 , 8.1 , 8.3 )
5.1Ocular Adverse Reactions TIVDAK can cause severe ocular adverse reactions, including conjunctivitis, keratopathy (keratitis, punctate keratitis, and ulcerative keratitis), and dry eye (increased lacrimation, eye pain, eye discharge, pruritus, irritation, and foreign body sensation), that may lead to changes in vision and/or corneal ulceration. Ocular adverse reactions occurred in 55% of patients with cervical cancer treated with TIVDAK across clinical trials. The most common ocular adverse reactions were conjunctivitis (32%), dry eye (24%), keratopathy (17%), and blepharitis (5%).
Grade 3 ocular adverse reactions occurred in 3.3% of patients, including severe ulcerative keratitis in 1.2% of patients. Nine patients (2.1%) experienced ulcerative keratitis (including one with perforation requiring corneal transplantation), six (1.4%) conjunctival ulcer, four (0.9%) corneal erosion, two (0.5%) conjunctival erosion, and two (0.5%) symblepharon. The median time to onset of the first ocular adverse reaction was 1.2 months (range, 0-17.1).
Of the patients who experienced ocular events, 59% had complete resolution and 31% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade) at last follow up. Ocular adverse reactions led to permanent discontinuation of TIVDAK in 6% of patients with cervical cancer. In innovaTV 301, 8 (3.2%) patients experienced delayed ocular adverse reactions occurring more than 30 days after discontinuation of TIVDAK.
These adverse reactions included 3 patients with ulcerative keratitis, and one patient (each) with keratitis, punctate keratitis and corneal erosion, blepharitis and conjunctival hyperemia, conjunctival scar, and conjunctivitis and xerophthalmia. Refer patients to an eye care provider to conduct an ophthalmic exam prior to initiation of TIVDAK, prior to every cycle for the first nine cycles, and as clinically indicated. The exam should include visual acuity, slit lamp exam of the anterior segment of the eye, and an assessment of normal eye movement and ocular signs or symptoms which include dry or irritated eyes, eye secretions or blurry vision.
Adhere to the required premedication and eye care before, during, and after infusion to reduce the risk of ocular adverse reactions [see Dosage and Administration (2.2) ]. Monitor for ocular toxicity and promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold, reduce, or permanently discontinue TIVDAK based on the severity or persistence of the ocular adverse reaction [see Dosage and Administration (2.3) ].
5.2Peripheral Neuropathy Peripheral neuropathy occurred in 39% of patients with cervical cancer treated with TIVDAK across clinical trials; 6% of patients experienced Grade 3 peripheral neuropathy. Perip…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: • Ocular Adverse Reactions [see Boxed Warning , Warnings and Precautions (5.1) ] • Peripheral Neuropathy [see Warnings and Precautions (5.2) ] • Hemorrhage [see Warnings and Precautions (5.3) ] • Pneumonitis [see Warnings and Precautions (5.4) ] • Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5) ] The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased, peripheral neuropathy, conjunctival adverse reactions, nausea, fatigue, aspartate aminotransferase increased, epistaxis, alopecia, alanine aminotransferase increased, and hemorrhage.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Seagen Inc. at 1-855-4SEAGEN 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. The data in the WARNINGS AND PRECAUTIONS section reflect exposure to TIVDAK in 425 patients with recurrent or metastatic cervical cancer who received at least one dose of TIVDAK at 2 mg/kg intravenously every 3 weeks in innovaTV 301, innovaTV 204, innovaTV 201 (NCT02001623), innovaTV 202 (NCT02552121), innovaTV 203 (NCT03245736), and innovaTV 206 (NCT03913741).
The median duration of treatment with TIVDAK was 3.7 months (range: 0.4-40.2). In this pooled safety population, the most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (45%), peripheral neuropathy (39%), conjunctival adverse reactions (38%), nausea (37%), fatigue (36%), aspartate aminotransferase increased (33%), epistaxis (33%), alopecia (31%), alanine aminotransferase increased (30%), and hemorrhage (28%). The data described in this section reflect exposure to TIVDAK from innovaTV 301 and innovaTV 204. innovaTV 301 The safety of TIVDAK was evaluated in an open-label, randomized study in patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy [see Clinical Studies (14.1) ].
A total of 250 patients received TIVDAK 2 mg/kg every 3 weeks until disease progression or unacceptable toxicity. The median duration of treatment with TIVDAK was 3.7 months (range: 0.4-19). Serious adverse reactions occurred in 33% of patients receiving TIVDAK.
The most common (≥2%) serious adverse reactions were urinary tract infection (4.8%), small intestinal obstruction (2.4%), sepsis (2%), abdominal pain (2%), and hemorrhage (2%). Fatal adverse reactions occurred in 1.6% of patients who received TIVDAK, including acute kidney injury (0.4%), pneumonia (0.4%), sepsis (0.4%) and Stevens-Johnson syndrome (0.4%). Adverse reactions leading to permanent discontinuation occurred in 15% of patients receiving TIVDAK; the most common (≥3%) adverse reactions leading to permanent discontinuation were peripheral neuropathy (6%) and ocular adverse reactions (6%).
Adverse reactions leading to dose interruption occurred in 39% of patients receiving TIVDAK; the most common (≥3%) adverse reactions leading to dose interruption were ocular adverse reactions (16%) and peripheral neuropathy (6%). Adverse reactions leading to dose reduction occurred in 30% of patients receiving TIVDAK; the most common (≥3%) adverse reactions leading to dose reduction were peripheral neuropathy (10%) and ocular adverse reactions (10%). The ocular adverse reactions included conjunctival disorders (4.8%), keratopathy (4%), and dry eye (0.8%).
The most common (≥25%) adverse reactions, including laboratory abnormalities, in patients receiving TIVDAK were hemoglobin decreased, peripheral neuropathy, conjunctival adverse reactions, aspartate aminotransferase increased, nausea, alanine aminotransferase increased, fatigue, sod…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Closely monitor for TIVDAK adverse reactions. ( 7.1 )
7.1Effects of Other Drugs on TIVDAK Strong CYP3A4 Inhibitors MMAE is a CYP3A4 substrate. Concomitant use of TIVDAK with strong CYP3A4 inhibitors may increase unconjugated MMAE exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for adverse reactions of TIVDAK when used concomitantly with strong CYP3A4 inhibitors.
🔄 Drug / Laboratory Test Interactions ▾
7.1Effects of Other Drugs on TIVDAK Strong CYP3A4 Inhibitors MMAE is a CYP3A4 substrate. Concomitant use of TIVDAK with strong CYP3A4 inhibitors may increase unconjugated MMAE exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for adverse reactions of TIVDAK when used concomitantly with strong CYP3A4 inhibitors.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Moderate or severe hepatic impairment: Exposure to MMAE and adverse reactions are increased. Avoid use. ( 8.6 ) • Lactation: Advise women not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary Based on the mechanism of action and findings in animals, TIVDAK can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available human data on TIVDAK use in pregnant women to inform a drug-associated risk. In an animal reproduction study, administration of the small molecule component of TIVDAK, MMAE, to pregnant rats during organogenesis caused embryo-fetal mortality and structural abnormalities at exposures below the clinical exposure at the recommended dose (see Data ) .
Advise patients of the potential risk to a fetus. The 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 No embryo-fetal development studies in animals have been performed with tisotumab vedotin-tftv. In an embryo-fetal development study in pregnant rats, administration of two intravenous doses of MMAE, the small molecule component of TIVDAK, on gestational days 6 and 13 caused embryo-fetal mortality and structural abnormalities, including protruding tongue, malrotated limbs, gastroschisis, and agnathia compared to controls at a dose of 0.2 mg/kg (approximately 0.5-fold the human area under the curve [AUC] at the recommended dose).
8.2Lactation Risk Summary There are no data on the presence of tisotumab vedotin-tftv in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment with TIVDAK and for 3 weeks after the last dose.
8.3Females and Males of Reproductive Potential TIVDAK can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ]. Pregnancy testing Verify pregnancy status in females of reproductive potential prior to initiating TIVDAK treatment. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose.
Males Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose. Infertility Females Based on findings in animal studies with MMAE-containing antibody-drug conjugates (ADCs), TIVDAK may impair female fertility. The effect on fertility is reversible [see Nonclinical Toxicology (13.1) ].
Males Based on findings from animal studies, TIVDAK may impair male fertility [see Nonclinical Toxicology (13.1) ].
8.4Pediatric Use Safety and effectiveness of TIVDAK in pediatric patients have not been established. Nonclinical studies of tisotumab vedotin-tftv suggest a lack of anti-tumor activity and penetrance to brain based on limited in vivo data from tissue factor (TF)-expressing subcutaneous or orthotopic pediatric models of high‑grade gliomas/glioblastomas (HGG/GBM) and diffuse intrinsic pontine glioma (DIPG).
8.5Geriatric Use Of the 425 patients with cervical cancer treated with TIVDAK across clinical trials, 14% were ≥65 years of age and 2.4% were ≥75 years of age. Grade ≥3 adverse reactions occurred in 60% of patients ≥65 years and in 55% of patients <65 years. Drug was discontinued due to an adverse reaction in 25% of patients ≥65 years and in 13% of patients <65 years.
Clinical studies of TIVDAK did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients.
8.6Hepatic Impairment Avoid use of TIVDAK in patients with moderate or severe hepatic impairment [aspartate amin…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on the mechanism of action and findings in animals, TIVDAK can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available human data on TIVDAK use in pregnant women to inform a drug-associated risk. In an animal reproduction study, administration of the small molecule component of TIVDAK, MMAE, to pregnant rats during organogenesis caused embryo-fetal mortality and structural abnormalities at exposures below the clinical exposure at the recommended dose (see Data ) .
Advise patients of the potential risk to a fetus. The 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 No embryo-fetal development studies in animals have been performed with tisotumab vedotin-tftv. In an embryo-fetal development study in pregnant rats, administration of two intravenous doses of MMAE, the small molecule component of TIVDAK, on gestational days 6 and 13 caused embryo-fetal mortality and structural abnormalities, including protruding tongue, malrotated limbs, gastroschisis, and agnathia compared to controls at a dose of 0.2 mg/kg (approximately 0.5-fold the human area under the curve [AUC] at the recommended dose).
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of TIVDAK in pediatric patients have not been established. Nonclinical studies of tisotumab vedotin-tftv suggest a lack of anti-tumor activity and penetrance to brain based on limited in vivo data from tissue factor (TF)-expressing subcutaneous or orthotopic pediatric models of high‑grade gliomas/glioblastomas (HGG/GBM) and diffuse intrinsic pontine glioma (DIPG).
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 425 patients with cervical cancer treated with TIVDAK across clinical trials, 14% were ≥65 years of age and 2.4% were ≥75 years of age. Grade ≥3 adverse reactions occurred in 60% of patients ≥65 years and in 55% of patients <65 years. Drug was discontinued due to an adverse reaction in 25% of patients ≥65 years and in 13% of patients <65 years.
Clinical studies of TIVDAK did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Tisotumab vedotin-tftv is a tissue factor (TF)-directed antibody drug conjugate (ADC). The antibody is a human IgG1 directed against cell surface TF. TF is the primary initiator of the extrinsic blood coagulation cascade.
The small molecule, MMAE, is a microtubule-disrupting agent, attached to the antibody via a protease-cleavable linker. Nonclinical data suggests that the anticancer activity of tisotumab vedotin-tftv is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death.
In vitro, tisotumab vedotin-tftv also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.
12.2Pharmacodynamics Tisotumab vedotin-tftv exposure-response relationships and the time course of pharmacodynamics response have not been fully characterized. Cardiac Electrophysiology At the recommended dose, tisotumab vedotin-tftv had no large mean effect on QTc prolongation (>20 msec).
12.3Pharmacokinetics Table 8 summarizes the exposure parameters of tisotumab vedotin-tftv and unconjugated MMAE (the cytotoxic component of tisotumab vedotin-tftv) following administration of one 3-week cycle of tisotumab vedotin-tftv 2 mg/kg to patients. Tisotumab vedotin-tftv concentrations peaked near the end of the infusion, while unconjugated MMAE concentrations peaked approximately 2 to 3 days after tisotumab vedotin-tftv dosing. Tisotumab vedotin-tftv C max increased proportionally, while AUC0-last increased in a more than dose-proportional manner, after a single dose ranging from 0.3–2.2 mg/kg (0.15 to 1.1 times the approved recommended dose).
There was no accumulation of tisotumab vedotin-tftv and unconjugated MMAE. Steady-state concentrations of tisotumab vedotin-tftv and unconjugated MMAE were reached after 1 treatment cycle. Table 8.
Exposure Parameters of Tisotumab Vedotin-tftv and Unconjugated MMAE C max =maximum concentration, AUC = area under the concentration-time curve from time 0 to 21 days (3 weeks) Tisotumab Vedotin-tftv Mean (± SD) Unconjugated MMAE Mean (± SD) C max 40.8 (8.12) μg/mL 5.91 (4.2) ng/mL AUC 57.5 (13.4) day*μg/mL 50 (35.8) day*ng/mL Distribution The tisotumab vedotin-tftv steady state volume of distribution is 7.83 (%CV: 19.1) L. Plasma protein binding of MMAE ranged from 68% to 82%, in vitro. Elimination The median terminal half-life of tisotumab vedotin-tftv and unconjugated MMAE is 4.04 (range: 2.26-7.25) days and 2.56 (range: 1.81-4.10) days, respectively.
The linear clearance of tisotumab vedotin-tftv and unconjugated MMAE was 1.54 (%CV: 28.8) L/day and 45.9 (%CV: 61.1) L/day, respectively. Elimination of MMAE appeared to be limited by its rate of release from tisotumab vedotin-tftv. Metabolism Tisotumab vedotin-tftv is expected to undergo catabolism to small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE-related catabolites.
Tisotumab vedotin-tftv releases unconjugated MMAE via proteolytic cleavage, and unconjugated MMAE is primarily metabolized by CYP3A4 in vitro. Excretion The excretion of tisotumab vedotin-tftv is not fully characterized. Following a single-dose of another ADC that contains MMAE, 17% of the total MMAE administered was recovered in feces and 6% in urine over a 1-week period, primarily as unchanged drug.
A similar excretion profile of MMAE is expected after tisotumab vedotin-tftv administration. Specific Populations No clinically significant differences in the pharmacokinetics of tisotumab vedotin-tftv were observed based on age (21 to 81 years), sex, race (white vs non-white) or ethnicity (Hispanic or Latino vs non-Hispanic or non-Latino). No clinically significant differences in exposures of tisotumab vedotin-tftv and unconjugated MMAE were observed in patients with mild to moderate renal im…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Tisotumab vedotin-tftv is a tissue factor (TF)-directed antibody drug conjugate (ADC). The antibody is a human IgG1 directed against cell surface TF. TF is the primary initiator of the extrinsic blood coagulation cascade.
The small molecule, MMAE, is a microtubule-disrupting agent, attached to the antibody via a protease-cleavable linker. Nonclinical data suggests that the anticancer activity of tisotumab vedotin-tftv is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death.
In vitro, tisotumab vedotin-tftv also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied TIVDAK (tisotumab vedotin-tftv) is supplied as a white to off-white lyophilized cake or powder in a 40 mg single-dose vial for reconstitution. TIVDAK vials are available in the following packages: • Carton of one 40 mg single-dose vial [NDC 51144-003-01] Storage Store TIVDAK vials refrigerated at 2ºC to 8ºC (36ºF to 46ºF) in the original carton to protect from light. Do not freeze.
Do not shake. Special Handling TIVDAK is a hazardous drug. Follow special handling and disposal procedures.
1
How Supplied TIVDAK (tisotumab vedotin-tftv) is supplied as a white to off-white lyophilized cake or powder in a 40 mg single-dose vial for reconstitution. TIVDAK vials are available in the following packages: • Carton of one 40 mg single-dose vial [NDC 51144-003-01]
📋 Description ▾
11 DESCRIPTION Tisotumab vedotin-tftv is a Tissue Factor (TF) directed antibody drug conjugate (ADC) comprised of a human anti-TF IgG1-kappa antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable vc (valine-citrulline) linker. The monoclonal antibody is produced in a mammalian cell line (Chinese hamster ovary). MMAE and the linker are produced by chemical synthesis.
Each monoclonal antibody molecule carries an average of 4 MMAE molecules. Tisotumab vedotin-tftv has an approximate molecular weight of 153 kDa. The chemical structure is as follows: Figure 1.
Structural Formula TIVDAK (tisotumab vedotin-tftv) for injection, is provided as a sterile, preservative-free, white to off-white lyophilized cake or powder in a single-dose vial for infusion after dilution. Following reconstitution with 4 mL of Sterile Water for Injection, a clear to slightly opalescent, colorless to brownish-yellow solution containing 10 mg/mL tisotumab vedotin-tftv is produced [see Dosage and Administration (2.3) ]. Each mL of reconstituted solution contains 10 mg of tisotumab vedotin-tftv, d-mannitol (30 mg), l-histidine (2.11 mg), l-histidine monohydrochloride (3.44 mg), and sucrose (30 mg), at pH 6.0.
Structural Formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Ocular Adverse Reactions • Inform patients about the eye exam they will receive with an eye care provider before starting TIVDAK, before each of the first nine cycles and as clinically indicated [see Warnings and Precautions (5.1) ] . • Inform patients about the ocular signs or symptoms the eye care provider will review before each cycle [see Warnings and Precautions (5.1) ] . • Inform patients that ocular adverse reactions may occur during treatment with TIVDAK and to contact their healthcare provider if they experience new or worsening ocular signs and symptoms [see Warnings and Precautions (5.1) ] . • Instruct patients to bring their eye drops to each infusion and advise on how to administer the eye drops throughout treatment [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ]. • Inform patients to avoid wearing contact lenses during treatment unless directed by an eye care provider [see Dosage and Administration (2.2) ].
Peripheral Neuropathy • Advise patients to report to their healthcare provider any numbness and tingling of the hands or feet or muscle weakness [see Warnings and Precautions (5.2) ]. Hemorrhage • Instruct patients to contact their healthcare provider to seek immediate medical attention for signs or symptoms of unusual severe bleeding or hemorrhage [see Warnings and Precautions (5.3) ]. Pneumonitis • Advise patients to immediately report new or worsening respiratory symptoms [see Warnings and Precautions (5.4) ].
Severe Cutaneous Adverse Reactions • Inform patients of the signs and symptoms of severe cutaneous adverse reactions, including life-threatening and potentially fatal SJS, which include target lesions, worsening skin reactions, blistering or peeling of the skin, painful sores in mouth, nose, throat, or genital area, fever or flu-like symptoms, and swollen lymph nodes [see Warnings and Precautions (5.5) ]. • Instruct patients to contact their healthcare provider to seek immediate medical attention for signs or symptoms of severe cutaneous adverse reactions, including SJS [see Warnings and Precautions (5.5) ].
Embryo-Fetal Toxicity • Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise patients to inform their healthcare providers of a known or suspected pregnancy [see Warnings and Precautions (5.6) and Use in Specific Populations (8.1) ]. • Advise females of reproductive potential to use effective contraception during treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose [see Use in Specific Populations (8.1 , 8.3) ].
Lactation • Advise women not to breastfeed during treatment with TIVDAK and for 3 weeks after the last dose [see Use in Specific Populations (8.2) ] . Manufactured by: Seagen Inc. Bothell, WA 98021 1-855-4SEAGEN Marketed by: Seagen Inc.
Bothell, WA 98021 and Genmab US, Inc. Plainsboro, NJ 08536 U.S. License 2257 TIVDAK ® is a trademark owned by Seagen Inc. ©2025 Seagen Inc. and Genmab US, Inc.
LAB-1596-1.0
💬 Medication Guide ▾
MEDICATION GUIDE This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 11/2025 MEDICATION GUIDE TIVDAK (TIV-dack) (tisotumab vedotin-tftv) for injection, for intravenous use What is the most important information I should know about TIVDAK?
TIVDAK can cause serious side effects, including: Eye problems . Eye problems are common with TIVDAK, and can also be severe. TIVDAK can cause changes to the surface of your eye that can lead to dry eyes, eye redness, eye irritation, corneal ulcers, blurred vision, and severe vision loss.
Tell your healthcare provider if you develop new or worsening vision changes or eye problems during treatment with TIVDAK. • Your healthcare provider will send you to an eye specialist to check your eyes before you start treatment with TIVDAK, before each infusion for your first 9 infusions of TIVDAK, and as needed for any new or worsening signs or symptoms of eye problems. • Your healthcare provider will ask if you have any signs or symptoms of eye problems before each infusion. You will be referred to an eye specialist for any new or worsening signs or symptoms of eye problems. • Your healthcare provider will prescribe 3 different types of eye drops before you start treatment with TIVDAK.
Bring the eye drops with you to each infusion and use them as directed by your healthcare provider to reduce your risk of eye problems: o Use 1 drop of steroid eye drops in each eye before each infusion and continue to use your eye drops 3 times a day for 3 days after each infusion. o Use vasoconstrictor eye drops right before each infusion. o Use lubricating eye drops throughout treatment and for 30 days after your last dose of TIVDAK. • Do not wear contact lenses throughout your treatment with TIVDAK unless you are told to use them by your eye specialist.
See “ What are the possible side effects of TIVDAK? ” for more information about side effects. What is TIVDAK? TIVDAK is a prescription medicine used to treat adults with cervical cancer: • that has returned or has spread to other parts of the body, and • who have received chemotherapy that did not work or is no longer working.
It is not known if TIVDAK is safe and effective in children. Before receiving TIVDAK, tell your healthcare provider about all of your medical conditions, including if you: • have a history of vision or eye problems • have numbness or tingling in your hands or feet • have bleeding problems • have liver problems • are pregnant or plan to become pregnant. TIVDAK can harm your unborn baby.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with TIVDAK. Females who are able to become pregnant: o Your healthcare provider should do a pregnancy test before you start treatment with TIVDAK. o You should use an effective birth control during treatment and for 2 months after your last dose of TIVDAK. Males with female partners who are able to become pregnant: o You should use an effective birth control during treatment and for 4 months after your last dose of TIVDAK. • are breastfeeding or plan to breastfeed.
It is not known if TIVDAK passes into your breast milk. Do not breastfeed during treatment and for 3 weeks after your last dose of TIVDAK. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Taking TIVDAK with certain other medicines may cause side effects. How will I receive TIVDAK? • TIVDAK will be given to you by intravenous (IV) infusion into your vein over 30 minutes. • TIVDAK is usually given every 3 weeks. • Your healthcare provider will decide how many infusions you need. • Your healthcare provider will put cold packs on your eyes during each infusion. • Your healthcare provider may decrease your dose, temporarily stop, or completely stop treatment with TIVDAK if you have side effects. What are the possible side effects of TIVDAK?
TIVDAK can cause s…