TIVDAK: Uses, Dosage & Side Effects
A first-in-class tissue factor-directed antibody-drug conjugate for adults with recurrent or metastatic cervical cancer that has progressed on or after chemotherapy
TIVDAK (tisotumab vedotin) is a first-in-class antibody-drug conjugate (ADC) approved for adult patients with recurrent or metastatic cervical cancer whose disease has progressed during or after chemotherapy. It pairs a fully human monoclonal antibody that recognizes tissue factor (TF), a protein highly expressed on cervical cancer cells, with the potent microtubule-disrupting cytotoxin monomethyl auristatin E (MMAE). Following intravenous infusion, the antibody binds tumor TF, the complex is internalized, and MMAE is released inside the cancer cell to trigger cell death. TIVDAK is administered every three weeks in a hospital or specialist oncology unit and requires a strict ocular monitoring and prophylaxis regimen because eye-related side effects, including potentially severe vision changes, are the most distinctive risk of the medicine.
Quick Facts: TIVDAK
Key Takeaways
- TIVDAK (tisotumab vedotin) is the first and only tissue factor-directed antibody-drug conjugate approved for recurrent or metastatic cervical cancer that has progressed on or after a prior systemic therapy.
- Treatment is given as a 30-minute intravenous infusion at a dose of 2.0 mg/kg (capped at 200 mg) every 3 weeks until disease progression or unacceptable toxicity, in a hospital or specialized oncology setting.
- Ocular adverse reactions, including conjunctival and corneal disorders and severe vision changes, are the most distinctive risks; a strict prophylactic eye-care regimen and an ophthalmologic exam before every cycle are mandatory.
- Other important risks include peripheral neuropathy, severe bleeding (hemorrhage), pneumonitis (interstitial lung disease), infusion-related reactions, and embryo-fetal toxicity that requires effective contraception in both women and men.
- In the confirmatory innovaTV 301 phase 3 trial, TIVDAK significantly improved overall survival compared with investigator-choice chemotherapy in previously treated cervical cancer, leading to full FDA approval in 2024.
What Is TIVDAK and What Is It Used For?
TIVDAK contains the active substance tisotumab vedotin, an antibody-drug conjugate (ADC) representing one of the most important advances in the treatment of cervical cancer in many years. It is a so-called "biological" cancer medicine that combines two functional components: a fully human monoclonal antibody that binds with high specificity to tissue factor (TF) on the surface of cancer cells, and a potent cytotoxic agent called monomethyl auristatin E (MMAE) attached to the antibody by a chemical linker. By engineering the antibody to act as a guided delivery vehicle, much of the MMAE is brought directly into TF-expressing tumor cells, where it can disrupt cell division while sparing many healthy tissues.
Tissue factor is a transmembrane protein best known for its central role in initiating the blood coagulation cascade after vascular injury. In many solid tumors, including cervical cancer, TF is aberrantly overexpressed on the surface of malignant cells and is also found on tumor blood vessels. High TF expression has been documented in the great majority of cervical cancers regardless of histology (squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma) and is associated with more aggressive disease behavior. This consistent overexpression makes TF an attractive therapeutic target, and TIVDAK was the first medicine of this kind to receive regulatory approval for any cancer indication.
Once TIVDAK binds to TF on a tumor cell, the entire antibody-drug complex is internalized into the cell through receptor-mediated endocytosis. Inside the cell, the protease-cleavable linker is cut by lysosomal enzymes (particularly cathepsin B), releasing MMAE into the cytoplasm. MMAE is a synthetic analogue of the natural product dolastatin 10 and is one of the most potent antimitotic agents known. It binds to tubulin and prevents the assembly of microtubules, the cellular structures required to separate chromosomes during cell division. Cells are arrested at the G2/M checkpoint of the cell cycle and ultimately die through apoptosis. Because MMAE is membrane-permeable, it can also diffuse from the targeted cell into neighboring tumor cells, producing a so-called "bystander" cytotoxic effect that may contribute to the activity of TIVDAK against tumors with heterogeneous TF expression.
TIVDAK is approved for adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. This includes patients who have been previously treated with platinum-based chemotherapy, with or without bevacizumab, and increasingly also patients who have received an immune checkpoint inhibitor such as pembrolizumab as part of earlier therapy. In this setting, treatment options have historically been limited and outcomes poor; TIVDAK is the first agent to demonstrate a clear overall survival benefit over chemotherapy in a randomized phase 3 trial in this difficult-to-treat population.
The U.S. Food and Drug Administration (FDA) first granted accelerated approval to TIVDAK in September 2021 based on the objective response rates observed in the innovaTV 204 phase 2 trial. Full traditional approval followed in April 2024 after the confirmatory innovaTV 301 phase 3 trial demonstrated a statistically significant improvement in overall survival compared with investigator-choice chemotherapy. The European Medicines Agency (EMA) and other regulatory authorities have also reviewed and authorized TIVDAK for the same indication.
Cervical cancer remains a major global health burden, causing more than 340,000 deaths each year worldwide according to the World Health Organization. Although effective screening and HPV vaccination programs have reduced incidence and mortality in countries with broad access to preventive care, the disease still presents in the recurrent or metastatic setting in many patients. After failure of platinum-based chemotherapy and immune checkpoint inhibitors, the prognosis is poor and effective second- and later-line options have been scarce. TIVDAK directly addresses this unmet medical need.
TIVDAK is not a traditional chemotherapy. The antibody portion is engineered to recognize tissue factor on cancer cells, and the MMAE payload is released preferentially inside those cells. This targeted approach concentrates the cell-killing effect at the tumor and reduces some toxicities associated with conventional chemotherapy, although it brings its own characteristic risks – particularly to the eyes – that require dedicated monitoring and prophylactic care.
What Should You Know Before Receiving TIVDAK?
Contraindications
Few absolute contraindications are listed for TIVDAK in the prescribing information. The principal contraindication is:
- Hypersensitivity: Do not receive TIVDAK if you have had a serious allergic reaction to tisotumab vedotin or to any of the inactive ingredients (histidine, histidine hydrochloride monohydrate, sucrose, and polysorbate 80).
In addition, the medicine should not be used in pregnancy unless the potential benefit clearly outweighs the substantial fetal risk, and several specific situations require treatment to be paused, dose-reduced, or permanently stopped (see Warnings and Precautions). Importantly, TIVDAK has not been studied in patients with severe hepatic impairment and is not recommended for those patients.
Warnings and Precautions
TIVDAK can cause severe eye problems, including conjunctival reactions, dry eye, corneal damage (such as ulcers or perforation), and severe vision changes including vision loss. A standardized ocular prophylaxis regimen is required for every infusion, and an ophthalmologic exam – including visual acuity and slit-lamp examination – must be performed at baseline, before each subsequent cycle, and as clinically indicated. Patients must avoid wearing contact lenses throughout treatment unless specifically authorized by their eye-care professional. Treatment must be withheld, dose-reduced, or permanently discontinued depending on the severity of any ocular event.
Before starting TIVDAK, your medical team will perform a baseline assessment that includes a complete ophthalmologic examination, blood tests (including complete blood count, liver and kidney function, coagulation), and a thorough review of your medications and medical history. During treatment, monitoring continues at every cycle. Inform your doctor immediately if any of the following develop or worsen.
Eye Problems (Ocular Toxicity)
Eye-related side effects are the hallmark of TIVDAK. They occur in the majority of patients in clinical trials and include conjunctivitis (red, watery, irritated eyes), dry eye, blurred vision, keratitis (inflammation or ulceration of the cornea), and changes in eyelid sensitivity. Severe events, including ulcerative keratitis, corneal scarring, and vision loss, have also been reported. To prevent and manage these problems, all of the following are required as part of standard practice:
- Baseline and pre-cycle eye exams by an eye-care professional, including visual acuity and slit-lamp examination.
- Ocular corticosteroid eye drops (e.g., dexamethasone 0.1%): one drop in each eye three times daily on the day of infusion (one dose immediately before the infusion is started) and continuing for 72 hours after the infusion.
- Vasoconstrictor eye drops (e.g., brimonidine tartrate 0.025% or 0.2%): one drop in each eye immediately before the infusion to reduce ocular drug exposure.
- Cooling eye pads: applied to both eyes during the entire infusion to reduce ocular drug delivery.
- Lubricating eye drops: used as needed several times a day during treatment and continued for 30 days after the last dose.
- Avoid contact lenses for the duration of treatment unless directed otherwise by an eye-care professional.
Tell your medical team immediately if you develop new eye redness, pain, light sensitivity, blurred vision, decreased vision, or any other change in vision. Many ocular events can be managed by withholding TIVDAK and giving additional treatment from an ophthalmologist; however, severe or recurrent events may require dose reduction or permanent discontinuation.
Peripheral Neuropathy
Like other MMAE-based ADCs, TIVDAK frequently causes peripheral neuropathy. Symptoms typically begin as numbness, tingling, or "pins and needles" sensations in the fingers and toes, and may progress to burning pain, weakness, or difficulty performing fine motor tasks such as buttoning a shirt. In severe cases neuropathy can affect walking and balance. Your doctor will assess your symptoms before each cycle and may delay treatment, reduce the dose, or stop TIVDAK depending on severity. Some neuropathy may improve after treatment ends, but in some patients it is long-lasting or permanent.
Hemorrhage (Bleeding)
Because tissue factor plays a central role in coagulation, treatment with a TF-targeted ADC carries an inherent risk of bleeding. The most common bleeding event observed with TIVDAK is epistaxis (nosebleeds), but more serious bleeding involving the gastrointestinal tract, the central nervous system, or the genitourinary tract has also been reported, including events with fatal outcomes. Tell your doctor about any history of bleeding problems, anti-coagulant or anti-platelet medications, recent surgery, or peptic ulcer disease. Watch for unusual bruising, blood in the urine or stool, prolonged nosebleeds, vaginal bleeding, or any sudden severe headache, and seek urgent medical care if these occur.
Pneumonitis and Interstitial Lung Disease
TIVDAK can cause severe and potentially life-threatening lung inflammation (pneumonitis or interstitial lung disease). Symptoms include new or worsening cough, shortness of breath, and chest discomfort. If pneumonitis is suspected, treatment should be withheld and appropriate diagnostic evaluation performed. Persistent or severe pneumonitis requires permanent discontinuation of TIVDAK.
Infusion-Related Reactions
Infusion-related reactions (IRRs) can occur during or shortly after the infusion. Symptoms include fever, chills, flushing, rash, itching, low blood pressure, shortness of breath, chest tightness, or nausea. Most reactions are mild to moderate and can be managed by slowing or temporarily stopping the infusion and giving symptomatic treatment such as antihistamines and corticosteroids. Severe reactions may require permanent discontinuation. Pre-medication may be considered for patients who have experienced a previous IRR.
Hepatic Impairment
Patients with mild or moderate hepatic impairment may experience higher exposure to MMAE and a greater risk of related toxicity, including neutropenia. TIVDAK has not been adequately studied in patients with severe hepatic impairment and is not recommended in this population. Liver function tests are routinely monitored before and during treatment.
Other Precautions
- Hematologic effects: Decreases in hemoglobin, lymphocytes, and platelets are commonly seen on routine blood work. Severe cytopenias are uncommon with monotherapy but may require treatment delays or dose modification.
- Infections: As with any cytotoxic therapy, the risk of infection is increased. Tell your doctor immediately if you develop fever, chills, persistent cough, painful urination, or other signs of infection.
- Driving and operating machinery: TIVDAK may cause blurred vision, fatigue, and peripheral neuropathy that can impair the ability to drive or use machines. Do not drive or operate machinery if you experience these symptoms until they have resolved.
- Vaccinations: Live attenuated vaccines should generally be avoided during treatment due to the risk of disseminated infection in the setting of immunosuppression. Discuss vaccination plans with your oncologist.
Other Medications
Tell your doctor about all medicines you are currently taking or have recently taken, including prescription medicines, over-the-counter products, herbal supplements, and vitamins. The MMAE component released from TIVDAK is metabolized by the cytochrome P450 enzyme CYP3A4 and is also a substrate of P-glycoprotein, so concomitant use of strong CYP3A4 inhibitors or P-gp inhibitors may increase MMAE exposure and toxicity, while strong inducers may decrease it.
Pregnancy, Breastfeeding, and Fertility
TIVDAK can cause serious harm or death to a developing fetus when given to a pregnant woman. The cytotoxic component MMAE is teratogenic and embryotoxic in animal studies. Your doctor will check pregnancy status before starting treatment in any woman of reproductive potential.
- Women of reproductive potential must use effective contraception during treatment and for at least 7 months after the last dose of TIVDAK.
- Men with female partners of reproductive potential must use effective contraception during treatment and for at least 4 months after the last dose, due to the potential for genotoxic effects.
- Breastfeeding is not recommended during treatment with TIVDAK and for at least 3 weeks after the final dose, as it is not known whether the medicine or its components are excreted in human milk and a risk to the breastfed infant cannot be excluded.
- Fertility: Based on findings in animals, TIVDAK may impair fertility in both men and women. Patients who wish to preserve fertility should discuss options such as oocyte cryopreservation or sperm banking before initiating therapy.
How Does TIVDAK Interact with Other Drugs?
Drug-drug interactions with TIVDAK primarily involve the cytotoxic payload MMAE, which is released inside cancer cells but also circulates in low concentrations in the body after each infusion. MMAE is metabolized predominantly by CYP3A4 in the liver and intestine and is transported by P-glycoprotein, so any drug that strongly affects these pathways may alter MMAE exposure. Although the antibody portion is too large to undergo classical drug-drug interactions, biological interactions related to bleeding, immunosuppression, and ocular toxicity should also be considered.
Major Interactions
| Interacting Drug or Class | Effect | Clinical Significance |
|---|---|---|
| Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, cobicistat) | Increased plasma concentrations of unconjugated MMAE; greater risk of neuropathy, neutropenia, and other MMAE-related toxicities | Avoid where possible; if unavoidable, monitor closely for adverse reactions and consider dose modification |
| Strong CYP3A4 inducers (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, St John's wort) | Decreased MMAE plasma levels; potentially reduced anti-tumor activity | Avoid if possible; consider alternative non-inducing therapy |
| P-glycoprotein (P-gp) inhibitors (e.g., verapamil, ciclosporin, quinidine) | Possible increase in MMAE exposure | Use with caution; monitor for additive toxicity |
| Live attenuated vaccines (e.g., MMR, varicella, yellow fever, BCG, oral polio) | Risk of vaccine-strain infection due to immunosuppression | Avoid during treatment and until immune recovery; inactivated vaccines are generally preferred |
Other Notable Interactions
| Interacting Drug or Class | Effect | Clinical Significance |
|---|---|---|
| Anticoagulants (e.g., warfarin, DOACs) and antiplatelets (e.g., aspirin, clopidogrel) | Additive bleeding risk; TIVDAK alone is associated with hemorrhage including epistaxis and serious bleeding events | Use with caution; weigh thrombotic vs bleeding risk; monitor for bleeding signs |
| Other neurotoxic agents (e.g., platinum compounds, taxanes, vinca alkaloids) | Additive peripheral neuropathy risk | Most patients have already received these as prior therapy; baseline neuropathy must be assessed before starting TIVDAK |
| Topical ocular medications not part of the prophylaxis regimen | May interfere with the standardized eye-care regimen or mask ocular toxicity | Discuss any other eye drops with the oncology team and ophthalmologist |
| Other immunosuppressive or myelosuppressive therapies | Additive immunosuppression and risk of infection | Combined use should be avoided unless specifically planned by the oncology team |
| Moderate CYP3A4 inhibitors (e.g., erythromycin, fluconazole, diltiazem, grapefruit juice) | Possible modest increase in MMAE exposure | Monitor for increased side effects; consider alternatives if available |
Always provide your oncology team and your community pharmacist with an up-to-date list of every medicine, herbal product, and over-the-counter remedy you take. New prescriptions, including those from unrelated specialists or in the emergency department, should be cross-checked against your TIVDAK treatment plan. Even short courses of common antibiotics or antifungals can interact significantly with the MMAE pathway.
What Is the Correct Dosage of TIVDAK?
TIVDAK is always prescribed and administered by clinicians experienced in cancer therapy and in the management of complex biological agents. Each cycle is carefully planned to combine the infusion itself with the mandatory ocular prophylaxis regimen and pre-cycle ophthalmologic assessment. Skipping any of these steps significantly increases the risk of serious side effects.
Standard Dose for Adults
Adults with Recurrent or Metastatic Cervical Cancer (Monotherapy)
Indication: Recurrent or metastatic cervical cancer that has progressed on or after chemotherapy
Dose: 2.0 mg/kg actual body weight, given by intravenous infusion over 30 minutes
Maximum dose: 200 mg per infusion (for patients weighing 100 kg or more, dose is calculated as if body weight were 100 kg)
Schedule: Once every 3 weeks (Day 1 of each 21-day cycle)
Duration: Continue until disease progression or unacceptable toxicity. There is no fixed maximum number of cycles.
Mandatory Ocular Prophylaxis Regimen
Before, during, and after every infusion, a structured eye-care regimen must be followed to reduce the risk and severity of ocular adverse reactions. This regimen is part of the dosing schedule and must not be omitted.
| Timing | Eye Care | Purpose |
|---|---|---|
| Before each cycle | Eye examination by an eye-care professional, including visual acuity and slit-lamp examination | Detect any new or worsening eye changes that require treatment delay or modification |
| Day of infusion (before) | One drop of vasoconstrictor eye drops (e.g., brimonidine 0.025% or 0.2%) in each eye immediately prior to infusion | Reduce blood flow and ocular drug delivery to the eye surface |
| During infusion | Cooling eye pads applied to both eyes during the entire 30-minute infusion | Vasoconstriction further reduces ocular drug exposure |
| Day of infusion and 72 hours after | Ocular corticosteroid drops (e.g., dexamethasone 0.1%) one drop in each eye three times daily | Reduce inflammation of the conjunctiva and cornea |
| Throughout treatment and 30 days after the last dose | Lubricating eye drops (preservative-free) used as needed several times per day | Manage dryness and protect the ocular surface |
| Throughout treatment | No contact lenses unless explicitly cleared by the eye-care professional | Avoid mechanical irritation and corneal complications |
Dose Modifications
The treating oncologist may need to delay treatment, reduce the dose, or discontinue TIVDAK in response to specific adverse events. Two recommended dose reductions are typically used: from 2.0 mg/kg to 1.3 mg/kg as the first reduction, and from 1.3 mg/kg to 0.9 mg/kg as the second reduction. If a third dose reduction would otherwise be required, treatment is permanently discontinued.
| Adverse Reaction | Severity | Recommended Action |
|---|---|---|
| Ocular events (conjunctival or corneal) | Grade 2 | Withhold until improvement to baseline or Grade 1; resume at the same or reduced dose based on ophthalmologist input |
| Ocular events | Grade 3 | Withhold until Grade 1; resume at reduced dose; permanently discontinue if recurrent at Grade 3 |
| Ocular events | Grade 4 (e.g., severe vision loss, ulcerative keratitis with perforation) | Permanently discontinue |
| Peripheral neuropathy | Grade 2 | Withhold until Grade 1; resume at the same or reduced dose |
| Peripheral neuropathy | Grade 3 or higher | Permanently discontinue |
| Hemorrhage | Grade 2 | Withhold until resolution to Grade 1 |
| Hemorrhage | Grade 3 or higher | Permanently discontinue |
| Pneumonitis | Grade 2 | Withhold and consider corticosteroids; resume at reduced dose if recovered |
| Pneumonitis | Grade 3 or higher (or recurrent) | Permanently discontinue |
| Infusion-related reaction | Grade 1–2 | Slow or interrupt infusion; consider pre-medication for future cycles |
| Infusion-related reaction | Grade 3 or higher | Stop infusion and permanently discontinue |
Special Populations
Children and Adolescents
The safety and efficacy of TIVDAK in children and adolescents below 18 years of age have not been established. The medicine is not recommended for use in this age group outside of clinical trials. Cervical cancer is rare in this population, and the indication for TIVDAK is limited to adults.
Elderly Patients
No overall differences in safety or effectiveness have been observed between elderly patients and younger adults in clinical trials, although greater susceptibility to adverse events in some older individuals cannot be excluded. Comorbid conditions, polypharmacy, and baseline ocular or neurologic disease may all influence treatment decisions.
Patients with Renal Impairment
No dose adjustment is recommended for patients with mild, moderate, or severe renal impairment based on available data. TIVDAK has not been studied in patients on dialysis.
Patients with Hepatic Impairment
Patients with mild hepatic impairment may experience modestly increased exposure to MMAE and a higher risk of certain side effects, but no formal dose adjustment is recommended. There is limited information for patients with moderate hepatic impairment, and TIVDAK is not recommended for patients with severe hepatic impairment.
Missed Dose
Because TIVDAK is administered in a clinic by a healthcare professional, a "missed dose" usually means a planned infusion that has been delayed for clinical reasons (such as pending recovery from a side effect or scheduling issues). The treating oncologist will reschedule the dose as soon as it is safe and clinically appropriate. Patients are advised not to miss any planned eye examinations or other monitoring visits, as these are critical to the safe continuation of therapy.
Overdose
There is no specific antidote for tisotumab vedotin. In case of suspected overdose, patients are monitored closely for any adverse reactions and treated supportively. Specific monitoring should focus on ocular toxicity, peripheral neuropathy, hematologic effects, and signs of bleeding or pneumonitis. Because TIVDAK is administered exclusively in a supervised clinical setting, overdose situations are exceptionally rare.
TIVDAK is always prepared and administered by trained healthcare professionals in a hospital or specialist oncology clinic. It must not be self-administered, and all monitoring – including blood tests, eye examinations, and clinical assessments – must be performed on schedule to ensure the safest possible treatment.
What Are the Side Effects of TIVDAK?
Like all medicines, TIVDAK can cause side effects, although not every patient will experience them. The pattern of side effects in clinical trials is dominated by ocular events and peripheral neuropathy, both of which can be reduced or managed through the standardized prophylaxis regimen, careful monitoring, and proactive dose adjustment. The frequencies below are based on the pivotal innovaTV 204 (phase 2) and innovaTV 301 (phase 3) trials and the prescribing information from regulatory authorities. They reflect adverse reactions of any severity unless otherwise noted.
Side Effects by Frequency
Very Common
May affect more than 1 in 10 people
- Conjunctivitis (red, watery, irritated eyes)
- Dry eye and ocular surface disease
- Keratitis (corneal inflammation)
- Blurred vision
- Peripheral neuropathy (numbness, tingling, pain, weakness in hands or feet)
- Epistaxis (nosebleeds)
- Alopecia (hair loss)
- Nausea
- Fatigue or weakness
- Decreased appetite
- Constipation or diarrhea
- Vomiting
- Abdominal pain
- Decreased hemoglobin (anemia)
- Decreased lymphocyte count
- Increased aspartate aminotransferase (AST)
- Increased alanine aminotransferase (ALT)
- Increased creatinine
- Increased prothrombin INR / activated partial thromboplastin time
- Decreased magnesium
- Headache
Common
May affect up to 1 in 10 people
- Severe (Grade 3 or higher) ocular reactions, including ulcerative keratitis
- Eyelid irritation, blepharitis, photophobia (light sensitivity)
- Severe peripheral neuropathy requiring dose modification
- Hematuria (blood in the urine), genitourinary bleeding
- Gastrointestinal bleeding
- Pneumonitis or interstitial lung disease
- Cough, dyspnea (shortness of breath)
- Infusion-related reactions (fever, chills, rash, hypotension, dyspnea)
- Stomatitis (mouth sores)
- Decreased neutrophil count (neutropenia)
- Decreased platelet count (thrombocytopenia)
- Insomnia (difficulty sleeping)
- Dizziness, taste disturbance (dysgeusia)
- Pyrexia (fever)
- Weight loss
- Pruritus (itching), rash
- Arthralgia (joint pain) and myalgia (muscle pain)
Uncommon
May affect up to 1 in 100 people
- Severe vision loss or blindness
- Corneal ulceration or perforation
- Severe hemorrhage including intracranial bleeding (rare and potentially fatal)
- Severe pneumonitis or interstitial lung disease leading to respiratory failure
- Severe infusion reactions including anaphylaxis
- Sepsis or septic shock related to immunosuppression
- Severe hepatic enzyme elevations
Not Known
Frequency cannot be estimated from available data
- Long-term ocular sequelae such as persistent visual impairment
- Long-term or permanent peripheral neuropathy
- Effects on fertility (predicted from animal data; not formally measured in humans)
How Side Effects Are Managed
Most side effects can be managed without permanently stopping TIVDAK if they are recognized early and addressed promptly. Patients are encouraged to keep a simple symptom diary between cycles, especially noting any new eye discomfort, vision changes, numbness or tingling, bleeding, or breathing problems. Telephone access to a specialist nurse or oncology team between visits is an important part of safe management.
For ocular events, the eye-care professional may add additional treatments such as longer-duration corticosteroid drops, antibiotic drops if infection is suspected, or specialist referral for severe events. Bandage contact lenses or amniotic membrane therapy have been used in selected cases of severe corneal involvement. For peripheral neuropathy, dose modification is the principal intervention; supportive medications such as duloxetine or gabapentin may help with painful neuropathic symptoms. Bleeding events are evaluated for cause; nasal saline rinses, humidified air, and avoidance of nasal trauma reduce the frequency of nosebleeds.
If you experience any side effects, including those not listed here, tell your doctor or nurse. You can also report suspected side effects to your national pharmacovigilance authority (e.g., the EMA in Europe, the FDA MedWatch program in the United States, or the MHRA Yellow Card Scheme in the United Kingdom) to help monitor the ongoing benefit-risk profile of TIVDAK.
How Should TIVDAK Be Stored?
Because TIVDAK is administered exclusively in a hospital or specialist clinic, all storage and preparation are managed by the hospital pharmacy and the oncology nursing team. Patients are not expected to handle vials at home. The instructions below summarize what is done behind the scenes to ensure each infusion is safe and effective.
- Unopened vials: Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze and do not shake.
- Light protection: Keep vials in the original carton until the time of preparation to protect from light.
- Reconstitution: Vials are reconstituted in the pharmacy with sterile water for injection following the prescribing information. The reconstituted solution should be a clear to slightly opalescent, colorless to pale yellow liquid. Do not use if discoloration or particulate matter is observed.
- Diluted infusion: The reconstituted dose is added to a sterile infusion bag of sodium chloride 0.9%, glucose 5%, or lactated Ringer's solution. The diluted infusion may be stored at 2°C to 8°C and used within 24 hours from the time of reconstitution; in-use room-temperature limits are described in the official product information.
- Disposal: Any unused medicine or waste material should be disposed of in accordance with local cytotoxic-waste handling requirements. Do not dispose of medicines via wastewater or household waste.
Do not use TIVDAK after the expiry date stated on the vial label and outer carton (after EXP). The expiry date refers to the last day of that month. Always keep medicines out of the sight and reach of children – this is a general principle for any pharmaceutical product even though TIVDAK is not dispensed to patients for home use.
What Does TIVDAK Contain?
Active Substance
The active substance is tisotumab vedotin, an antibody-drug conjugate composed of a fully human IgG1-kappa monoclonal antibody targeted against tissue factor, conjugated through a protease-cleavable maleimidocaproyl-valine-citrulline (mc-vc) linker to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE). Each single-use vial contains 40 mg of tisotumab vedotin.
The antibody portion of tisotumab vedotin is produced in mammalian (Chinese hamster ovary) cell culture using recombinant DNA technology. The MMAE payload is conjugated to the antibody at a defined drug-to-antibody ratio, with an average of approximately 4 MMAE molecules per antibody molecule. The molecular weight of the resulting conjugate is approximately 153 kDa.
Inactive Ingredients (Excipients)
- L-Histidine
- L-Histidine hydrochloride monohydrate
- Sucrose
- Polysorbate 80
These excipients act as buffers, stabilizers, and surfactants to maintain the integrity and activity of the antibody-drug conjugate during storage and preparation. They are widely used in modern biological medicines and are generally well tolerated, although individuals with a known polysorbate hypersensitivity should inform their medical team.
Appearance
TIVDAK is supplied as a white to off-white lyophilized cake or powder in a clear glass single-use vial with an elastomeric stopper, an aluminum seal, and a plastic flip-off cap. After reconstitution with sterile water for injection, the solution is clear to slightly opalescent, colorless to pale yellow, and free from visible particles. Each carton typically contains one single-use vial.
Manufacturer and Marketing Authorization
TIVDAK was originally developed by Genmab in collaboration with Seagen Inc. Following the acquisition of Seagen by Pfizer in 2023, the medicine is now marketed by Pfizer in collaboration with Genmab in major regulatory regions. Detailed manufacturer and authorization-holder information for your region is provided on the outer carton of the product and in the official product information.
Frequently Asked Questions About TIVDAK
TIVDAK (tisotumab vedotin) is used to treat adults with recurrent or metastatic cervical cancer whose disease has progressed during or after chemotherapy. It is the first and only tissue factor-directed antibody-drug conjugate approved for any cancer indication. It is intended as a treatment for advanced disease that is no longer responding to platinum-based chemotherapy and (in many cases) immune checkpoint inhibition.
Eye-related side effects are the most distinctive risk of TIVDAK. To prevent and manage these problems, a structured ocular regimen is mandatory: cooling eye pads worn during the entire infusion, vasoconstrictor drops just before each infusion, ocular corticosteroid drops on the day of infusion and for 72 hours after, and lubricating drops several times daily. An eye examination by an eye-care professional is performed at baseline, before every cycle, and as needed. Contact lenses must be avoided throughout treatment unless your eye-care professional says otherwise.
TIVDAK is given as an intravenous (IV) infusion over 30 minutes once every 3 weeks (Day 1 of each 21-day cycle). The standard dose is 2.0 mg/kg of body weight, capped at 200 mg per infusion for patients weighing 100 kg or more. Treatment continues until the cancer worsens or unacceptable side effects develop. The infusion is administered by trained healthcare professionals in a hospital or specialized clinic.
Severe ocular events, including vision loss, have been reported with TIVDAK, although they are uncommon when the standardized prophylaxis regimen is followed and pre-cycle eye examinations are performed. Most ocular reactions are mild to moderate and improve with treatment delays, additional eye drops, and ophthalmologist input. Patients should report any new eye redness, pain, light sensitivity, or change in vision immediately so that early action can be taken.
TIVDAK can affect fertility in both women and men. Animal studies suggest that the cytotoxic component MMAE may damage reproductive cells. Women of reproductive potential must use effective contraception during treatment and for at least 7 months after the last dose, and men with female partners of reproductive potential must use effective contraception during treatment and for at least 4 months after the last dose. Patients who wish to preserve fertility should discuss options such as oocyte cryopreservation or sperm banking before starting therapy.
In the pivotal innovaTV 301 phase 3 trial, TIVDAK significantly improved overall survival compared with investigator-choice chemotherapy in patients with recurrent or metastatic cervical cancer who had received prior systemic therapy. Median overall survival was approximately 11.5 months with TIVDAK versus 9.5 months with chemotherapy, with a roughly 30% reduction in the risk of death. Objective response rates were also higher with TIVDAK (around 18%) compared with chemotherapy (around 5%). These results converted the initial accelerated FDA approval into full approval in 2024.
TIVDAK is currently approved as a single-agent (monotherapy) treatment for recurrent or metastatic cervical cancer. Combinations with immune checkpoint inhibitors such as pembrolizumab and with other agents are being investigated in ongoing clinical trials, including in earlier lines of therapy. Outside of a clinical trial, TIVDAK should be used as a single agent in line with the approved labelling. Decisions about sequencing it with other therapies are made by the treating oncologist based on the most current evidence and the individual patient's situation.
References
- U.S. Food and Drug Administration (FDA). TIVDAK (tisotumab vedotin-tftv) Prescribing Information. Revised 2024. Available from: FDA Drug Label.
- European Medicines Agency (EMA). Tivdak (tisotumab vedotin) – Public Assessment Report and Summary of Product Characteristics. 2025. Available from: EMA.
- Vergote I, González-Martín A, Fujiwara K, et al. Tisotumab Vedotin as Second- or Third-Line Therapy for Recurrent Cervical Cancer (innovaTV 301 / ENGOT-cx12 / GOG-3057). N Engl J Med. 2024;391(1):44–55. doi:10.1056/NEJMoa2313375.
- Coleman RL, Lorusso D, Gennigens C, et al. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6). Lancet Oncol. 2021;22(5):609–619. doi:10.1016/S1470-2045(21)00056-5.
- Hong DS, Concin N, Vergote I, et al. Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer (innovaTV 201). Clin Cancer Res. 2020;26(6):1220–1228. doi:10.1158/1078-0432.CCR-19-2962.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Cervical Cancer. Version 1.2025.
- Marth C, Tarney CM, Long HJ, et al. ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of cervical cancer. Ann Oncol. 2024;35(3):217–234.
- World Health Organization (WHO). Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem. Geneva: WHO; 2020.
- Markham A. Tisotumab Vedotin: First Approval. Drugs. 2021;81(18):2141–2147. doi:10.1007/s40265-021-01633-8.
- Hoffman-Censits J, Lombardo KA, Parimi V, et al. Tissue factor expression in cervical and other gynecologic cancers: rationale for tisotumab vedotin. Gynecol Oncol. 2022;165(1):151–157.
Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in gynecologic oncology, clinical pharmacology, and ocular toxicity management.
Medical Content
iMedic Gynecologic Oncology Editorial Team – specialist physicians with clinical experience in cervical cancer treatment and antibody-drug conjugates
Medical Review
iMedic Medical Review Board – independent panel verifying accuracy against FDA Prescribing Information, EMA SmPC, NCCN, and ESMO guidelines
Pharmacology Review
iMedic Clinical Pharmacology Team – specialists in drug interactions, pharmacokinetics, and medication safety for biological therapies
Accessibility & SEO
iMedic Digital Health Team – ensuring WCAG 2.2 AAA compliance and optimal search visibility
All content follows the GRADE evidence framework and is reviewed according to international medical guidelines. iMedic receives no commercial funding from pharmaceutical companies.