Tisotumab vedotin-tftv

Tisotumab vedotin-tftv
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tejasvi Aryaputra

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Black Box Warning

TITLE See full prescribing information for complete Boxed Warning. Condition Name: (Content)

Overview

Tisotumab vedotin-tftv is a tissue factor-directed antibody and microtubule inhibitor conjugate that is FDA approved for the treatment of recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include peripheral neuropathy, alopecia, epistaxis, leukocytes decreased, creatinine increased, dry eye, activated partial thromboplastin time prolonged, hemoglobin decreased, conjunctival adverse reactions, hemorrhage, fatigue, lymphocytes decreased, nausea, prothrombin international normalized ratio increased, rash, and diarrhea..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

• 2 mg/kg is the recommended dosage of Tisotumab_vedotin-tftv through an intravenous infusion.
• Dosage should be given for 30 minutes every 3 weeks.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Tisotumab vedotin-tftv in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Tisotumab vedotin-tftv in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Tisotumab_vedotin-tftv FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Tisotumab vedotin-tftv in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Tisotumab vedotin-tftv in pediatric patients.

Contraindications

There are no contraindications associated with Tisotumab_vedotin-tftv.

Warnings

TITLE See full prescribing information for complete Boxed Warning. Condition Name: (Content)

Ocular Adverse Reactions

• Clinical studies show that 60% of patients with cervical cancer reported ocular adverse reactions when taking Tisotumab_vedotin-tftv.
• Of the patients with ocular adverse reactions, patients reported corneal adverse reactions (21%), conjunctival adverse reactions (40%), blepharitis (8%), and dry eye (29%) are the most common.
• 3.8% of patients reported grade 3 ocular adverse reactions.
• Corneal transplantation was required in one patient with signs of ulcerative keratitis with perforation when taking Tisotumab_vedotin-tftv.
• 1.2 months was the median time of onset for patients that had first ocular adverse.
• 55% of patients who had ocular events displayed complete resolution.
• 30% of patients who had ocular events showed partial resolution which is defined as a decrease in severity by one or more grades from the worst grade.
• 6% of patients with cervical cancer discontinued use of Tisotumab_vedotin-tftv when patients showed signs of ocular adverse reactions.
• Visual acuity changes to 20/50 or worse was seen in 4% of patients in innovaTV 204 where 75% had resolution this issue.
• Visual acuity change to 20/200 was seen in 1% of patients in innovaTV 204 of the patients that had visual acuity changes to 20/50 or worse.
• Advise patients prior to each dose of Tisotumab_vedotin-tftv to get an ophthalmic exam.
• Monitor patients slit lamp exam and visual acuity at baseline.
• Advise patients to report any signs and symptoms of new or worsening ocular reactions.
• Advise patients with adverse reactions to permanently discontinue, withhold, or reduce the dose of Tisotumab_vedotin-tftv based on the severity.

Peripheral Neuropathy

• 42% of patients with cervical cancer displayed peripheral neuropathy when taking Tisotumab_vedotin-tftv.
• 8% of patients with peripheral neuropathy displayed Grade 3 peripheral neuropathy.
• Of the patients with peripheral neuropathy, peripheral sensory neuropathy (11%), motor neuropathy (3%), demyelinating peripheral polyneuropathy (1%), peripheral neuropathy (20%), peripheral sensorimotor neuropathy (5%), and muscular weakness (3%) are the most common adverse reactions reported in patients.
• Guillain-Barre syndrome was reported in one patient with another tumor type when taking Tisotumab_vedotin-tftv.
• 2.4 months is the median time to onset in patients that displayed peripheral neuropathy.
• 17% of patients who had peripheral neuropathy displayed complete resolution.
• 17% of patients who had peripheral neuropathy showed partial improvement which is defined as a decrease in severity by one or more grades from the worst grade.
• 8% of patients with cervical cancer discontinued use of Tisotumab_vedotin-tftv when patients showed signs of peripheral neuropathy.
• Advise patients about signs and symptoms of peripheral neuropathy such as neuropathic pain, muscle weakness, tingling or a burning sensation, dysesthesia, or paresthesia.
• Advise patients with adverse reactions to permanently discontinue, withhold, or reduce the dose of Tisotumab_vedotin-tftv based on the severity.

Hemorrhage

• 62% of patients with cervical cancer reported Hemorrhage when taking Tisotumab_vedotin-tftv.
• Of the patients that reported signs of Hemorrhage, hematuria (10%), epistaxis (44%), and vaginal hemorrhage (10%).
• Of the patients that reported signs of Hemorrhage, 5% of patients displayed signs and symptoms of Grade 3 hemorrhage.
• 0.3 months is the median time to onset in patients with hemorrhage taking Tisotumab_vedotin-tftv.
• 71% of patients who had hemorrhage displayed complete resolution.
• 11% of patients who had hemorrhage events showed partial resolution which is defined as a decrease in severity by one or more grades from the worst grade.
• Monitor patients that display any signs and symptoms of hemorrhage.
• Permanently discontinue the use of Tisotumab_vedotin-tftv when experiencing pulmonary or CNS hemorrhage.
• Withhold treatment or permanently discontinue the use of Tisotumab_vedotin-tftv based on the severity of grade ≥2 hemorrhage.

Pneumonitis

• Signs of Severe, life-threatening, or fatal pneumonitis has been reported in patients when using antibody drug conjugates containing vedotin including Tisotumab_vedotin-tftv.
• Clinical studies showed 1.3% patients displayed signs of pneumonitis where one patient in the study had a fatal outcome of pneumonitis.
• Monitor patients for signs of pneumonitis such as dyspnea, cough, interstitial infiltrates on radiologic exam, or hypoxia.
• Dose reductions of Tisotumab_vedotin-tftv may occur if patients display persistent or recurrent Grade 2 pneumonitis.
• Patients that display Grade 3 or 4 pneumonitis should permanently discontinue the use of Tisotumab_vedotin-tftv.

Embryo-Fetal Toxicity

• Fetal harm may occur in pregnant women taking Tisotumab_vedotin-tftv based on animal studies.
• MMAE caused structural abnormalities and embryo-fetal mortality in rats.
• Advise females about potential risks to a fetus when taking Tisotumab_vedotin-tftv.
• Advise females of reproductive potential to use effective contraception during treatment with Tisotumab_vedotin-tftv and for at least 2 months after the last dose.
• Advise males of reproductive potential to use effective contraception during treatment with Tisotumab_vedotin-tftv and for at least 4 months after the last dose.

Adverse Reactions

Clinical Trials Experience

Clinical Trial Experiance

• Because clinical trials are conducted under widely varying conditions and durations of follow up, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reactions of Tisotumab_vedotin-tftv was looked into 158 patients with recurrent or metastatic cervical cancer. These patients all received at least one dose of Tisotumab_vedotin-tftv at 2 mg/kg intravenously every 3 weeks in innovaTV 201 (NCT02001623), innovaTV 203 (NCT03245736), innovaTV 202 (NCT02552121), and innovaTV 204 (NCT03438396).

InnovaTV 204 Study

• 43% of patients displayed serious adverse reactions from the innovaTV 204. Of the patients that displayed serious adverse reactions included pneumonia (4%), ileus (6%), peripheral neuropathy (3%), pyrexia (3%), hemorrhage (5%), sepsis (3%), and constipation (3%) were the most common.
• 4% of patients taking Tisotumab_vedotin-tftv displayed fatal adverse reactions. Some of the fatal adverse reactions included pneumonitis (1%), multisystem organ failure (1%), sudden death (1%), and septic shock (1%).
• 13% of patients had to permanently discontinue Tisotumab_vedotin-tftv treatment when experiencing adverse reactions. Corneal adverse reactions (4%) and peripheral neuropathy (5%) were the most common adverse reactions in patients who had to discontinue Tisotumab_vedotin-tftv treatment.
• 47% of patients had dose interruption with Tisotumab_vedotin-tftv treatment when experiencing adverse reactions. Hemorrhage (4%), peripheral neuropathy (8%), and conjunctival adverse reactions (4%) were the most common adverse reactions in patients who had dose interruption with Tisotumab_vedotin-tftv treatment.
• 23% of patients had dose reduction with Tisotumab_vedotin-tftv treatment when experiencing adverse reactions. Corneal adverse reactions (9%) and conjunctival adverse reactions (8%) were the most common adverse reactions in patients who had dose reduction with Tisotumab_vedotin-tftv treatment.
• In laboratory abnormalities, nausea, peripheral neuropathy, alopecia, epistaxis, hemorrhage, leukocytes decreased, creatinine increased, dry eye, prothrombin international normalized ratio increased, activated partial thromboplastin time prolonged, hemoglobin decreased, fatigue, lymphocytes decreased, conjunctival adverse reactions, diarrhea, and rash were the most common adverse reactions (≥25%) when taking Tisotumab_vedotin-tftv.

Table 4 summarizes InnovaTV 204 Adverse Reactions.

Insert Table 4

Table 5 summarizes InnovaTV 204 Laboratory Abnormalities.

Insert Table 5

Immunogenicity

• Tisotumab_vedotin-tftv may have an immune response. Specificity and sensitivity of the assay play a role in the formation of antibodies against Tisotumab vedotin-tftv. Assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease are factors that influence the positivity of antibody incidence.
• Immunogenicity of Tisotumab_vedotin-tftv was tested in 93 patients in the InnovaTV 204 study.

Postmarketing Experience

There is limited information about "Postmarketing Experiance" in the drug label.

Drug Interactions

There is limited information regarding Tisotumab vedotin-tftv Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Tisotumab vedotin-tftv in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Tisotumab vedotin-tftv in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Tisotumab vedotin-tftv during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Tisotumab vedotin-tftv in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Tisotumab vedotin-tftv in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Tisotumab vedotin-tftv in geriatric settings.

Gender

There is no FDA guidance on the use of Tisotumab vedotin-tftv with respect to specific gender populations.

Race

There is no FDA guidance on the use of Tisotumab vedotin-tftv with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Tisotumab vedotin-tftv in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Tisotumab vedotin-tftv in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Tisotumab vedotin-tftv in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Tisotumab vedotin-tftv in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Tisotumab vedotin-tftv Administration in the drug label.

Monitoring

There is limited information regarding Tisotumab vedotin-tftv Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Tisotumab vedotin-tftv and IV administrations.

Overdosage

There is limited information regarding Tisotumab vedotin-tftv overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Tisotumab vedotin-tftv Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Tisotumab vedotin-tftv Mechanism of Action in the drug label.

Structure

There is limited information regarding Tisotumab vedotin-tftv Structure in the drug label.

Pharmacodynamics

There is limited information regarding Tisotumab vedotin-tftv Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Tisotumab vedotin-tftv Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Tisotumab vedotin-tftv Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Tisotumab vedotin-tftv Clinical Studies in the drug label.

How Supplied

There is limited information regarding Tisotumab vedotin-tftv How Supplied in the drug label.

Storage

There is limited information regarding Tisotumab vedotin-tftv Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Tisotumab vedotin-tftv Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Tisotumab vedotin-tftv interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Tisotumab vedotin-tftv Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Tisotumab vedotin-tftv Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.