Tivdak

About Tisotumab vedotin-tftv

• Tisotumab vedotin, marketed as Tivdak, represents an antibody-drug conjugate employed in the treatment of cervical cancer. 
• This advanced therapeutic agent integrates tisotumab, a monoclonal antibody specifically targeting tissue factor, with monomethyl auristatin E (MMAE), a potent inhibitor of cell division. 
• Tisotumab administration is achieved through intravenous infusion.
• In September 2021, Tisotumab vedotin received approval for medical use in the United States, earning recognition from the U.S. Food and Drug Administration as a first-in-class medication. 
• Tisotumab vedotin-tftv stands out as a tissue factor (TF)-directed antibody drug conjugate (ADC), featuring a human IgG1 antibody directed against the cell surface TF, a primary initiator of the extrinsic blood coagulation cascade. 
• The small molecule MMAE, acting as a microtubule-disrupting agent, is intricately linked to the antibody through a protease-cleavable linker.
• Nonclinical data underscores that the anticancer efficacy of tisotumab vedotin-tftv is rooted in the binding of the ADC to TF-expressing cancer cells. 
• This process is succeeded by the internalization of the ADC-TF complex, leading to the subsequent release of MMAE through proteolytic cleavage. 
• MMAE, in turn, disrupts the microtubule network of actively dividing cells, inducing cell cycle arrest and apoptotic cell death. 
• Complementing these mechanisms, in vitro studies reveal that tisotumab vedotin-tftv facilitates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

Strength: 

The injection is available as a 40 mg lyophilized cake or powder in a single-dose vial for reconstitution. 

Recommended Dosage:

Ophthalmic examinations, including visual acuity and slit lamp assessments, should be conducted at baseline, before each Tivdak dose, and as clinically indicated. Prescribe and renew corticosteroid eye drops after a slit lamp examination, administering the first drop in each eye before each infusion. Instruct patients to continue using prescribed eye drops for 72 hours post-infusion. Administer topical ocular vasoconstrictor drops before each infusion and use cooling eye pads during Tivdak infusion. Additionally, advise patients to apply lubricating eye drops throughout the therapy and for 30 days after the last Tivdak dose. Caution patients against wearing contact lenses unless advised by their eye care provider for the entire treatment duration.

Tivdak is to be administered exclusively as an intravenous infusion, emphasizing its classification as a hazardous drug and necessitating adherence to specific handling and disposal protocols. The reconstitution process involves using Sterile Water for Injection, with subsequent dilution in an intravenous infusion bag containing 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection. Reconstituted vials may be refrigerated for up to 24 hours or stored at room temperature for a maximum of 8 hours before dilution, with a strict prohibition on freezing. The infusion, administered over 30 minutes through an intravenous line with a 0.2 µm in-line filter, necessitates confirmation of prior administration of steroid and vasoconstrictor eye drops. 

Cold packs are to be applied over the eyes during the infusion, changed as necessary to maintain the desired cooling effect. Storage of the diluted Tivdak solution in refrigeration is specified, with a 4-hour time limit for completion of administration once removed from refrigeration. Rigorous visual inspections for particulate matter and discoloration are emphasized throughout the preparation process, with any abnormalities leading to the discard of the respective vials or infusion bags.

• Avoid administering Tivdak through intravenous push or bolus, and refrain from combining it with or administering it concurrently with other medicinal products. 
• The recommended dosage of Tivdak is 2 mg/kg (up to a maximum of 200 mg), delivered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity occurs.

Important:

Prior to initiating Tivdak injection, promptly communicate any adverse reactions to your doctor. If you observe unusual symptoms while undergoing treatment, consult your doctor immediately. Share details of pre-existing health conditions before commencing treatment, ensuring comprehensive information for safe administration. Maintaining open communication about your health is essential for personalized care and addressing any concerns that may arise during the treatment process.

Warnings & Precautions

• Do not take this medicine if you are allergic to Tisotumab vedotin-tftv or any of its ingredients. 
• Peripheral neuropathy should be diligently monitored in patients receiving Tivdak for any indications of new or worsening symptoms. 
• Adjustments in treatment, such as withholding, dose reduction, or permanent discontinuation of Tivdak, should be considered based on the severity of peripheral neuropathy. 
• Additionally, vigilance is essential for detecting signs and symptoms of hemorrhage, and appropriate action, including withholding, dose reduction, or permanent discontinuation of Tivdak, should be taken in accordance with the severity observed. 
• Pneumonitis, which may be severe, life-threatening, or fatal, necessitates the withholding of Tivdak for persistent or recurrent Grade 2 pneumonitis, along with the consideration of dose reduction. Permanent discontinuation of Tivdak is recommended for Grade 3 or 4 pneumonitis. 
• Furthermore, caution is advised regarding embryo-fetal toxicity, emphasizing the potential harm to a fetus. Patients should be informed of this risk, and effective contraception should be utilized. 
• Close monitoring for adverse reactions is particularly crucial when Tivdak is co-administered with strong CYP3A4 inhibitors.

Common Tivdak Side Effects:

• Decreased red blood cell and white blood cell counts
• Tiredness
• Nausea
• Numbness/tingling in hands or feet, muscle weakness
• Hair loss
• Nosebleeds
• Eye problems (dry eyes, redness, irritation, corneal ulcers)
• Bleeding (increased risk of bruises, cuts, gum bleeding)
• Changes in kidney function blood tests
• Diarrhea
• Rash
• Constipation
• Fever
• Vomiting
• Cough
• Appetite loss
• Abdominal pain
• Dizziness
• Headache
• Difficulty sleeping
• Muscle/joint pain

Use in Specific Population

• Due to its mechanism of action and observed effects in animal studies, Tivdak has the potential to cause harm to a developing fetus if administered to pregnant women. 
• There is a lack of data on the presence of tisotumab vedotin-tftv in human milk, its impact on the breastfed child, or its effects on milk production. Considering the potential for severe adverse reactions in breastfed infants, lactating women are advised not to breastfeed during Tivdak treatment and for 3 weeks following the last dose. 
• It is essential to confirm the pregnancy status of females of reproductive potential before initiating Tivdak treatment.
• Contraception recommendations include advising females of reproductive potential to use effective contraception throughout Tivdak treatment and for 2 months after the final dose. 
• Male patients with female partners of reproductive potential should also use effective contraception during Tivdak treatment and for 4 months after the last dose. 
• Notably, Tivdak, based on animal studies, may adversely affect male fertility, as indicated in nonclinical toxicology data.
• Regarding pediatric use, the safety and effectiveness of Tivdak in pediatric patients remain undetermined, and its use is not recommended. 
• Additionally, Tivdak should be avoided in patients with moderate or severe hepatic impairment. For those with mild hepatic impairment, close monitoring for adverse reactions is advised, although no adjustment to the starting dose of Tivdak is recommended.

Storage and Handling

• Store them in a refrigerated environment at temperatures ranging from 2ºC to 8ºC (36ºF to 46ºF), within the original carton to shield them from light exposure. 
• Avoid freezing the vials and refrain from shaking them.
• Keep the medicine away from pets and children.