* 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]].
== Overview ==
'''Tisotumab vedotin''' is an [[antibody-drug conjugate]] (ADC) used in the treatment of certain types of [[cancer]]. It is designed to deliver a cytotoxic agent directly to [[tumor]] cells by targeting the [[tissue factor]] (TF) antigen, which is overexpressed in various [[malignancies]].
* 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.
== Mechanism of Action ==
Tisotumab vedotin consists of a [[monoclonal antibody]] that specifically binds to tissue factor, linked to a potent cytotoxic agent, [[monomethyl auristatin E]] (MMAE). Upon binding to the tissue factor on the surface of cancer cells, the ADC is internalized, and MMAE is released inside the cell, leading to [[microtubule]] disruption and subsequent [[apoptosis]] of the cancer cell.
[[File:Vedotin_ADCs.svg|thumb|right|Diagram of Vedotin ADCs]]
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== Clinical Applications ==
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Tisotumab vedotin is primarily used in the treatment of [[cervical cancer]] and is being investigated for use in other cancers such as [[ovarian cancer]], [[endometrial cancer]], and [[bladder cancer]]. Its ability to target tissue factor makes it a promising therapeutic option for tumors that express this antigen.
The development of tisotumab vedotin involved extensive [[clinical trials]] to evaluate its safety and efficacy. It has been granted [[accelerated approval]] by regulatory agencies for use in patients with recurrent or metastatic cervical cancer who have progressed on or after chemotherapy.
== '''What are the uses of this medicine?''' ==
== Side Effects ==
Common side effects of tisotumab vedotin include [[nausea]], [[fatigue]], [[alopecia]], and [[peripheral neuropathy]]. Serious adverse effects can include [[hemorrhage]], [[ocular toxicity]], and [[neutropenia]]. Patients receiving this treatment require careful monitoring for these potential complications.
Tisotumab vedotin ('''Tivdak''') is a prescription medicine used to treat adults with [[cervical cancer]]:
== Related Pages ==
* that has returned or has spread to other parts of the body, and
* [[Antibody-drug conjugate]]
* who have received [[chemotherapy]] that did not work or is no longer working.
* 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?''' ==
* {{overdose}}
== '''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.
Tisotumab vedotin is an antibody-drug conjugate (ADC) used in the treatment of certain types of cancer. It is designed to deliver a cytotoxic agent directly to tumor cells by targeting the tissue factor (TF) antigen, which is overexpressed in various malignancies.
Mechanism of Action
Tisotumab vedotin consists of a monoclonal antibody that specifically binds to tissue factor, linked to a potent cytotoxic agent, monomethyl auristatin E (MMAE). Upon binding to the tissue factor on the surface of cancer cells, the ADC is internalized, and MMAE is released inside the cell, leading to microtubule disruption and subsequent apoptosis of the cancer cell.
Diagram of Vedotin ADCs
Clinical Applications
Tisotumab vedotin is primarily used in the treatment of cervical cancer and is being investigated for use in other cancers such as ovarian cancer, endometrial cancer, and bladder cancer. Its ability to target tissue factor makes it a promising therapeutic option for tumors that express this antigen.
Development and Approval
The development of tisotumab vedotin involved extensive clinical trials to evaluate its safety and efficacy. It has been granted accelerated approval by regulatory agencies for use in patients with recurrent or metastatic cervical cancer who have progressed on or after chemotherapy.
