Tisotumab vedotin

What is Tisotumab vedotin?

• Tisotumab vedotin (Tivdak) is a tissue factor-directed antibody and microtubule inhibitor conjugate used to treat recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

• It is an antibody-drug conjugate (ADC) comprised of a monoclonal antibody against human tissue factor (TF) covalently coupled, via a protease-cleavable peptide linker, to monomethyl auristatin E (MMAE), an auristatin derivative and potent microtubule disrupting agent, with potential antiangiogenic, anticoagulant and antineoplastic activities.

What are the uses of this medicine?

Tisotumab vedotin (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.

How does this medicine work?

• Upon administration, tisotumab vedotin binds to cell surface TF and is internalized.
• The antibody moiety prevents binding of TF to factor VIIa (FVIIa) and interferes with the activation of factor X (FX) into FXa. This may prevent thrombin formation and cancer-associated venous thromboembolism, and may inhibit angiogenesis and tumor cell proliferation.
• After internalization of the agent, the MMAE moiety is released by proteolytic cleavage.
• It then binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and apoptosis.
• TF, a transmembrane protein and initiator of the coagulation cascade, is overexpressed in many tumor cells and tumor-resident endothelial cells.
• Expression of TF is correlated with metastasis, angiogenesis, tumor cell growth and tumor-associated thrombosis.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• Concomitant use of TIVDAK with strong CYP3A4 inhibitors may increase unconjugated MMAE exposure , which may increase the risk of TIVDAK adverse reactions.
• Closely monitor patients for adverse reactions of TIVDAK when used concomitantly with strong CYP3A4 inhibitors.

Is this medicine FDA approved?

• Tisotumab vedotin was approved for medical use in the United States in September 2021.

How should this medicine be used?

Recommended 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.

Administration:

• 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 dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection: 40 mg as a lyophilized cake or powder in a single-dose vial for reconstitution.

This medicine is available in fallowing brand namesː

• TIVDAK

What side effects can this medication cause?

The most common side effects of this medicine include:

• decreased red blood cell
• and white blood cell counts
• tiredness
• nausea
• hair loss (alopecia)
• nosebleed
• changes in kidney function blood tests
• dry eye
• abnormal blood clotting test results
• diarrhea
• rash

TIVDAK can cause serious side effects, including:

• Eye problems
• Peripheral neuropathy
• Bleeding (hemorrhage)
• Lung problems

What special precautions should I follow?

• Peripheral neuropathy occurred in patients with cervical cancer treated with TIVDAK. Monitor patients for new or worsening peripheral neuropathy. Withhold, reduce the dose, or permanently discontinue TIVDAK based on severity.
• Hemorrhage occurred in patients with cervical cancer treated with TIVDAK. Monitor patients for signs and symptoms of hemorrhage. Withhold, reduce the dose, or permanently discontinue TIVDAK based on severity.
• Severe, life-threatening, or fatal pneumonitis can occur in patients treated with antibody drug conjugates containing vedotin including TIVDAK. Withhold TIVDAK for persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK for Grade 3 or 4 pneumonitis.
• Based on the mechanism of action and findings in animals, TIVDAK can cause fetal harm when administered to a pregnant woman. Advise of the potential risk to a fetus and to use effective contraception.
• Ocular adverse reactions occurred in patients with cervical cancer treated with TIVDAK. Withhold, reduce the dose, or permanently discontinue TIVDAK based on the severity of the adverse reaction.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• Based on the mechanism of action and findings in animals, TIVDAK can cause fetal harm when administered to a pregnant woman.
• There are no available human data on TIVDAK use in pregnant women to inform a drug-associated risk.

Can this medicine be used in children?

• Safety and effectiveness of TIVDAK in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: tisotumab vedotin-tftv
• Inactive ingredients: d-mannitol, l-histidine, l-histidine monohydrochloride, and sucrose.

Who manufactures and distributes this medicine?

• Manufactured by: Seagen Inc., Bothell, WA 98021, 1-855-4SEAGEN
• Marketed by: Seagen Inc., Bothell, WA 98021 and Genmab US, Inc., Plainsboro, NJ

What should I know about storage and disposal of this medication?

• 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

• Dailymed label info on Tisotumab vedotin
• FDA Tisotumab vedotin

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