• Recurrent or metastatic cervical cancer with disease progression during or after chemotherapy.

Contraindicated in:

• Moderate or severe hepatic impairment
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: DEEP VEIN THROMBOSIS.

Derm: alopecia, pruritus, rash, STEVENS-JOHNSON SYNDROME (SJS).

EENT: blepharitis, conjunctival abrasion/erosion, conjunctival hemorrhage, conjunctival hyperemia, conjunctival scar, conjunctivitis, corneal bleeding, corneal erosion, corneal scar, dry eye, epistaxis, keratitis, ocular hyperemia, blepharitis.

Endo: hypoglycemia.

F and E: hypomagnesemia, hyponatremia.

GI: ↓ appetite, ↓ weight, ↑ liver enzymes, abdominal pain, constipation, diarrhea, hypoalbuminemia, nausea, vomiting, ileus.

GU: ↑ serum creatinine, urinary tract infection, ↓ fertility (males).

Hemat: ↑ activated partial thromboplastin time, ↑ prothrombin time, anemia, hemorrhage, leukopenia, lymphocytopenia, neutropenia.

Metab: hyperuricemia.

MS: ↑creatine kinase, arthralgia, myalgia, muscle weakness.

Neuro: fatigue, peripheral neuropathy.

Resp: pneumonia, PNEUMONITIS, PULMONARY EMBOLISM.

Misc: fever.

Drug-Drug:

• Strong CYP3A4 inhibitors, including ketoconazole, may ↑ levels and risk of toxicity of MMAE; monitor closely.

• Lyophilized powder for injection: 40 mg/vial;

• IV (Adults ≥100 kg): 200 mg every 3 wk; continue until disease progression or unacceptable toxicity.
• IV (Adults <100 kg): 2 mg/kg every 3 wk; continue until disease progression or unacceptable toxicity.

Tivdak

• Acts as an antibody-drug conjugate (ADC) composed of a human IgG1 monoclonal antibody that is directed against tissue factor (located on the cell surface of cancer cells). Monomethyl auristatin E (MMAE) (an agent that disrupts microtubles and subsequently causes apoptosis) is attached to the antibody via a cleavable linker. The ADC binds to tissue factor on the cancer cells; the complex is then internalized, and then the MMAE is cleaved and released inside the cancer cells.

• Reduced progression of recurrent or metastatic cervical cancer.

Therapeutic Classification: antineoplastics

Pharmacologic Classification:

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Monoclonal antibody component is degraded into smaller peptides via catabolism. MMAE is primarily metabolized in the liver via the CYP3A4 isoenzyme. 17% of MMAE excreted in feces, and 6% excreted in urine, primarily as unchanged drug.

Half-life: ADC: 4 days; MMAE: 2.5 days.

(plasma concentrations)

• Explain purpose of tisotumab to patient. Advise patient to read Medication Guide before starting and periodically during therapy in case of changes.
• Inform patient of potential eye problems and eye drop regimen. Instruct patient to use steroid eye drops before each infusion and as prescribed for 72 hr after each infusion. Instruct patient to use vasoconstrictor eye drops right before each infusion. Instruct patient to administer topical lubricating eye drops for duration of therapy and for 30 days after last dose of tisotumab. Advise patient to notify health care professional if new or worsening vision changes or eye problems develop during therapy.
• Advise patients to avoid wearing contact lenses unless advised by their eye care provider for the entire duration of therapy.
• Advise patient to notify health care professional immediately if signs and symptoms of bleeding (blood in stools or black stools, blood in urine, cough up or vomit blood, unusual vaginal bleeding, any unusual or heavy bleeding), lung problems (trouble breathing, shortness of breath, cough), severe skin reactions (skin reactions that look like rings [target lesions]; rash or itching that continues to get worse; blistering or peeling of skin; painful sores or ulcers in mouth, nose, throat, or genital area; fever or flu-like symptoms; swollen lymph nodes) or peripheral neuropathy (numbness in hands or feet, muscle weakness) occur.
• Discuss with patient the possibility of hair loss. Explore methods of coping. May also cause darkening of skin and fingernails.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 2 mo after last dose and to avoid breastfeeding during and for 3 wk after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for 4 mo after last dose. May impair male fertility.

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