Tisotumab Vedotin

Tisotumab Vedotin is a prescription medication used for the treatment of recurrent or metastatic cervical cancer in patients with disease progression during or following chemotherapy

• Tisotumab Vedotin is available under the following different brand names: Tivdak, Tisotumab Vedotin-tftv.

Common side effects of Tisotumab Vedotin include:

• decreased hemoglobin
• fatigue
• decreased lymphocytes
• nausea
• numbness and tingling in extremities
• hair loss
• nosebleed
• adverse eye reactions
• hemorrhage
• decreased leukocytes
• increased creatinine
• dry eye
• increased prothrombin international normalized ratio
• prolonged activated partial thromboplastin time
• diarrhea
• rash

Serious side effects of Tisotumab Vedotin include:

• unusual or heavy bleeding or bruising
• bloody, black, or tarry stools
• vomiting blood or material that looks like coffee grounds
• blood in the urine
• unusual vaginal bleeding
• nosebleed
• trouble breathing, shortness of breath, or cough
• numbness or tingling of the hands or feet; or muscle weakness, pain, or burning
• peripheral neuropathy (nerve problems)

Rare side effects of Tisotumab Vedotin include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injection, lyophilized powder for reconstitution

• 40 mg/vial

Cervical cancer

Adult dosage

• 2 mg/kg IV every 3 weeks; not to exceed 200 mg/dose for patients 100 kg and more
• Continue until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Tisotumab Vedotin has severe interactions with no other drugs
• Tisotumab Vedotin has serious interactions with no other drugs
• Tisotumab Vedotin has moderate interactions with at least 28 other drugs
• Tisotumab Vedotin has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Tisotumab Vedotin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Tisotumab Vedotin?”

Cautions

• Based on the mechanism of action and findings in animal studies, can cause fetal harm
• Peripheral neuropathy
  • Peripheral neuropathy reported
  • Median time to onset of peripheral neuropathy reported to be 2.4 months (range, 0-11.3 months)
  • Monitor for signs and symptoms of neuropathy (eg, paresthesia, tingling or burning sensation, neuropathic pain, muscle weakness, dysesthesia)
  • If observed, withhold the dose, then reduce the dose or permanently discontinue
• Hemorrhage
  • Hemorrhage occurred in a majority of treated patients
  • Median time to onset of hemorrhage reported to be 0.3 months (range, 0-6.5 months)
  • Monitor and withhold or discontinue dose as recommended
• Pneumonitis
  • Severe, life-threatening, or fatal pneumonitis can occur in patients treated with antibody-drug conjugates
  • Pulmonary symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic examinations; infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations
  • Monitor for pulmonary symptoms and adjust the dose, withhold treatment, or permanently discontinue as recommended
• Ocular adverse effects
  • Ocular adverse reactions reported; promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms
  • Conduct ophthalmic examination including visual acuity and slit lamp examination at baseline, before each dose, and as clinically indicated
  • Administer premedication and cold-pack regimen with each infusion
  • Common ocular adverse reactions included conjunctival adverse reactions (40%), dry eye (29%), corneal adverse reactions (21%), and blepharitis (8%)
  • Grade 3 ocular adverse reactions occurred in 3.8%, including severe ulcerative keratitis in 3.2% of patients
  • One patient experienced ulcerative keratitis with perforation requiring corneal transplantation
  • Symblepharon was reported in patients with other tumor types treated at the recommended dose
  • Median time to onset of the first ocular adverse reaction was 1.2 months
  • Among patients who experienced ocular events, 55% had complete resolution, 30% had partial improvement, 6% discontinued treatment
• Drug interaction overview
  • Strong CYP3A4 inhibitors
    • Monitor closely if coadministered
• Tisotumab Vedotin is metabolized to monomethyl auristatin E (MMAE), a mitotic inhibitor and the cytotoxic component of the antibody-drug conjugate
  • MMAE is a substrate of CYP3A4
• Strong CYP3A4 inhibitors may increase unconjugated MMAE systemic exposure and increase the risk of adverse effects

Pregnancy and Lactation

• Based on the mechanism of action and findings in animals, can cause fetal harm when administered to pregnant women
• Human data are not available to evaluate drug-associated risk
• Advise patients of potential risk to the fetus and verify pregnancy status in women of reproductive potential before initiating
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for 2 months after the last dose
  • Males with female partners of reproductive potential: Use effective contraception during treatment and for 4 months after the last dose
• Infertility
  • Males: Based on findings from animal studies, may impair fertility
• Lactation
  • Data are not available on the drug’s presence in human milk, its effects on breastfed children, or milk production
  • Advise lactating women not to breastfeed during treatment and for 3 weeks after the last dose