Cervical cancer

Active Ingredient: Tisotumab vedotin

Indication for Tisotumab vedotin

Population group: women, only adults (18 - 65 years old)

Therapeutic intent: Curative procedure

Tisotumab vedotin is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

For this indication, competent medicine agencies globally authorize below treatments:

2 mg/kg once every 3 weeks

For:

Dosage regimens

Intravenous, 2 milligrams tisotumab vedotin per kilogram of body weight, once every 3 weeks.

Detailed description

The recommended dose 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.

Premedication and required eye care

Adhere to the following recommendations to reduce the risk of ocular adverse reactions.

Ophthalmic exam by eye care provider: Conduct an ophthalmic exam prior to initiation of tisotumab vedotin, prior to every cycle for the first nine cycles, and as clinically indicated. The ophthalmic exam should include visual acuity, slit lamp exam of the anterior segment of the eye, and an assessment of normal eye movement.
Topical corticosteroid eye drops: Instruct patients to administer one drop in each eye prior to each infusion and to continue to administer eye drops in each eye three times daily for 72 hours after each infusion. The initial prescription and all renewals of any corticosteroid medication should be made only after examination with a slit lamp.
Topical ocular vasoconstrictor drops: Administer in each eye immediately prior to each infusion of tisotumab vedotin.
Cold packs: Use cooling eye pads during each infusion of tisotumab vedotin.
Topical lubricating eye drops: Instruct patients to administer for the duration of therapy and for 30 days after the last dose of tisotumab vedotin.
Contact lenses: Advise patients to avoid wearing contact lenses for the entire duration of therapy unless advised by their eye care provider.

Dosage modifications for adverse reactions

The recommended tisotumab vedotin dose reduction schedule is provided in Table 1.

Table 1. Dosage Reduction Schedule:

	Tisotumab vedotin Dose Level
Starting dose	2 mg/kg (up to a maximum of 200 mg for patients ≥100 kg)
First dose reduction	1.3 mg/kg (up to a maximum of 130 mg for patients ≥100 kg)
Second dose reduction	0.9 mg/kg* (up to a maximum of 90 mg for patients ≥100 kg)

^* Permanently discontinue in patients who cannot tolerate 0.9 mg/kg.

The recommended dose modifications for adverse reactions are provided in Table 2.

Table 2. Dosage Modifications for Adverse Reactions:

Adverse Reaction	Severity	Occurrence	TIVDAK Dose Modification
Keratitis*	Nonconfluent superficial keratitis	Any	Monitor.
	Confluent superficial keratitis, a corneal epithelial defect, or a 3 line or more loss in best corrected visual acuity	First occurrence	Withhold dose until resolution, or improvement to nonconfluent superficial keratitis, then resume treatment at the next lower dose level.
		Second occurrence	Permanently discontinue.
	Ulcerative keratitis or perforation	Any	Permanently discontinue.
Conjunctival or corneal scarring or symblepharon*	Any scarring or symblepharon	Any	Permanently discontinue.
Conjunctivitis and other ocular adverse reactions*	Nonconfluent superficial punctate conjunctival defects, mild vasodilation	Any	Monitor.
	Confluent superficial punctate conjunctival defects, moderate to severe vasodilation	First occurrence	Withhold dose until resolution or improvement to nonconfluent superficial punctate conjunctival defects, mild vasodilation, then resume treatment at the same dose.
		Second occurrence	Withhold dose until resolution or improvement to nonconfluent superficial punctate conjunctival defects, mild vasodilation, then resume treatment at the next lower dose level. If no resolution or improvement to nonconfluent superficial punctate conjunctival defects, mild vasodilation, permanently discontinue.
		Third occurrence	Permanently discontinue.
	Conjunctival ulcer, conjunctival neovascularization, or fibrovascular scarring	Any	Permanently discontinue.
Peripheral Neuropathy	Grade 2	Any (initial or worsening of pre-existing condition)	Withhold dose until Grade ≤1, then resume treatment at the next lower dose level.
Peripheral Neuropathy	Grade 3 or 4	Any	Permanently discontinue.
Hemorrhage	Any grade pulmonary or CNS	Any	Permanently discontinue.
	Grade 2 in any other location	Any	Withhold until resolved, then resume treatment at the same dose.
	Grade 3 in any other location	First occurrence	Withhold dose until resolved, then resume treatment at the same dose.
	Grade 3 in any other location	Second occurrence	Permanently discontinue.
	Grade 4 in any other location	Any	Permanently discontinue.
Pneumonitis	Grade 2	Any	Withhold dose until Grade ≤1 for persistent or recurrent pneumonitis, consider resuming treatment at next lower dose level.
Pneumonitis	Grade 3 or 4	Any	Permanently discontinue.
Severe cutaneous adverse reactions (including Stevens- Johnson syndrome (SJS))	Suspected (any grade)	Any	Immediately withhold dose and consult a specialist to confirm the diagnosis.
	Confirmed Grade 3 or 4	Any	Permanently discontinue.

^* Refer patients to an eye care provider promptly for an assessment of new or worsening ocular symptoms.

Active ingredient

Tisotumab vedotin
Tisotumab vedotin is a tissue factor (TF)-directed antibody drug conjugate (ADC). The antibody is a human IgG1 directed against cell surface TF. TF is the primary initiator of the extrinsic blood coagulation cascade. The small molecule, MMAE, is a microtubule-disrupting agent, attached to the antibody via a protease-cleavable linker. Nonclinical data suggests that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. Read more about Tisotumab vedotin

Related medicines

Structured Product Labeling (SPL/PLR) 2024: TIVDAK Solution for injection

Develop a tailored medication plan for your case, considering factors such as age, gender, and health history

Ask the Reasoner

Liability Disclaimer : RxReasoner has utilized reasonable care in providing content and services that are accurate, complete and up to date. However, RxReasoner does not accept any responsibility or liability about it. The content and services of RxReasoner are for informational purposes only and they are not intended to be a substitute for the knowledge, expertise, skill, and judgment of physicians, pharmacists, nurses, or other healthcare professionals involved in patient care. RxReasoner offers no medical advice. Users are responsible for the use of the provided content. A shown indication or treatment should not be construed to indicate that the medication is safe, appropriate, or effective in any given patient or under any particular circumstances. The absence of an indication or treatment should not roule out the existence of other appropriate medications. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition or medicament. RxReasoner is not liable for any damages allegedly sustained arising out of the use of its content and services.