Tisotumab vedotin

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Tisotumab vedotin
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetTissue factor (TF)
Names
Trade namesTivdak
Other namesTisotumab vedotin-tftv
Clinical data
Drug classAntineoplastic
Main usesCervical cancer[1]
Side effectsTiredness, nausea, peripheral neuropathy, hair loss, nose bleeds, kidney problems, eye problems, diarrhea, rash[1]
Pregnancy
category
  • Contraindicated[1]
Routes of
use
Intravenous
External links
AHFS/Drugs.comMonograph
US NLMTisotumab vedotin
Legal
License data
Legal status
Pharmacokinetics
Protein binding68–82% (MMAE)
MetabolismLiver, by CYP3A4 (MMAE)
MetabolitesMMAE
Elimination half-life4 days
ExcretionFecal, renal (MMAE)

Tisotumab vedotin, sold under the brand name Tivdak, is a medication used to treat cervical cancer.[1] It is used when other treatments are not effective.[1] It is given by gradual injection into a vein every 3 weeks.[1]

Common side effects include tiredness, nausea, peripheral neuropathy, hair loss, nose bleeds, kidney problems, eye problems, diarrhea, and rash.[1] Other side effects may include pneumonitis.[1] Use in pregnancy may harm the baby.[1] It is an antibody-drug conjugate, a combination of tisotumab, a monoclonal antibody against tissue factor, and monomethyl auristatin E (MMAE), an inhibitor of cell division.[1][2]

Tisotumab vedotin was approved for medical use in the United States in 2021.[1] As of 2022 it is not approved in Europe or the United Kingdom.[3] In the United States a dose of 120 mg costs about 19,300 USD as of 2022.[4]

Medical use

Dosage

It is given as 2 mg/kg, up to a dose of 200 mg, over half an hour every three weeks.[1]

Side effects

In the United States, it carries a black box warning for eye problems, which occurs in up to 60% of people.[1] The most common forms were dry eye, conjunctivitis, corneal damage, and blepharitis.[1]

To prevent eye damage, premedication with three different types of eye drops—a topical corticosteroid, a vasoconstrictor, and artificial tears—is recommended before each infusion, as well as the use of cold packs over the eyes.[1]

Other very common adverse effects include bleeding (occurring in approximately 60% of patients, most often nosebleed) and peripheral neuropathy (42% of patients).[1] Like all drugs containing MMAE, tisotumab vedotin can cause inflammation of the lungs.[1]

Mechanism of action

The antibody portion of tisotumab vedotin (tisotumab) binds to and forms a complex with tissue factor, a molecule expressed on the surface of cancer cells. This complex is then taken up into the cell, where tisotumab vedotin is broken down by proteolytic cleavage, releasing MMAE, which stops the cell cycle and kills the cell by apoptosis.[1]

History

Tisotumab was developed by Genmab in Utrecht, the Netherlands, and Copenhagen, Denmark, with the code name TF-011-MMAE.[5] It is marketed in a 50/50 partnership between Genmab and Seagen, which developed and owns the intellectual property for vedotin technology (monoclonal antibody–MMAE conjugates).

Tisotumab vedotin is the international nonproprietary name (INN).[6]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 "Tivdak- tisotumab vedotin injection, powder, for solution". DailyMed. Archived from the original on 1 November 2021. Retrieved 31 October 2021.
  2. "Tisotumab Vedotin-tftv Monograph for Professionals". Drugs.com. Retrieved 27 October 2022.
  3. "Tisotumab vedotin". SPS - Specialist Pharmacy Service. 16 January 2021. Archived from the original on 27 October 2022. Retrieved 27 October 2022.
  4. "Tivdak Prices, Coupons, Copay & Patient Assistance". Drugs.com. Retrieved 27 October 2022.
  5. Breij EC, de Goeij BE, Verploegen S, Schuurhuis DH, Amirkhosravi A, Francis J, Miller VB, Houtkamp M, Bleeker WK, Satijn D, Parren PW (February 2014). "An antibody-drug conjugate that targets tissue factor exhibits potent therapeutic activity against a broad range of solid tumors". Cancer Res. 74 (4): 1214–26. doi:10.1158/0008-5472.CAN-13-2440. PMID 24371232.
  6. World Health Organization (2016). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 75". WHO Drug Information. 30 (1): 159–60. hdl:10665/331046.

External links

Identifiers: