Tisotumab vedotin
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From MedlinePlus, U.S. National Library of Medicine
Specialty pharmacy: therapy management checklist, storage and cold chain, dosing calendar, Medicare Part D coverage.
Boxed warning
WARNING: OCULAR TOXICITY • TIVDAK can cause severe ocular toxicities resulting in changes in vision, including severe vision loss, and corneal ulceration. [see Warnings and Precautions (5.1) ]. • Conduct an ophthalmic exam, including an assessment of ocular symptoms, visual acuity, and slit lamp exam of the anterior segment of the eye prior to initiation of TIVDAK, prior to every cycle for the first nine cycles, and as clinically indicated. [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ] . • Adhere to the required premedication and eye care before, during, and after infusion. [see Dosage and Administration (2.2) ].
• Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) ]. WARNING: OCULAR TOXICITY See full prescribing information for complete boxed warning. • TIVDAK can cause severe ocular toxicities resulting in changes in vision, including severe vision loss and corneal ulceration. ( 5.1 ) • Conduct an ophthalmic exam, including an assessment of ocular symptoms, visual acuity, and slit lamp exam of the anterior segment of the eye prior to initiation of TIVDAK, prior to every cycle for the first nine cycles, and as clinically indicated.
( 2.2 , 5.1 ) • Adhere to the required premedication and eye care before, during, and after infusion. ( 2.2 ) • Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity. ( 2.3 , 5.1 )
Handling and access
NIOSH hazardous drug
Table 1NIOSH lists tisotumab-vedotin as a hazardous drug. AHFS class: 10:00 antineoplastic agents.
- The package insert includes manufacturer's special handling information (MSHI). Follow it when preparing, administering, and disposing of this drug.
- Biologic (Biologics License Application).
Handle with the precautions your facility uses for hazardous drugs (USP <800>). NIOSH's Managing Hazardous Drug Exposures lists controls by drug form and activity.
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Dosing in liver impairment
Hepatic Impairment Avoid use of TIVDAK in patients with moderate or severe hepatic impairment [aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN) or total bilirubin > 1.5 × ULN] [see Clinical Pharmacology ]. In patients with mild hepatic impairment (total bilirubin ≤ ULN and AST >ULN or total bilirubin > 1 to 1.5 × ULN and any AST), closely monitor patients for adverse reactions of TIVDAK, but no dosage adjustment in the starting dose of TIVDAK is recommended.
Preparation and administration
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Instructions for Preparation and Administration
Administer TIVDAK as an intravenous infusion only.
TIVDAK is a hazardous drug. Follow applicable special handling and disposal procedures 1 .
DO NOT administer TIVDAK as an intravenous push or bolus.
DO NOT mix TIVDAK with, or administer as an infusion with, other medicinal products. Use appropriate aseptic technique for reconstitution and preparation of dosing solutions. Prior to administration, the TIVDAK vial is reconstituted with Sterile Water for Injection, USP. The reconstituted solution is subsequently diluted in an intravenous infusion bag containing one of the following: 5% Dextrose Injection USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer’s Injection, USP.
Reconstitution in Single-dose Vial 1. Calculate the recommended dose based on the patient’s weight to determine the number of vials needed. 2. Reconstitute each 40 mg vial with 4 mL of Sterile Water for Injection, USP, resulting in 10 mg/mL TIVDAK. 3. Slowly swirl each vial until the contents are completely dissolved. Allow the reconstituted vial(s) to settle.
DO NOT SHAKE THE VIAL. Do not expose to direct sunlight. 4. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The reconstituted solution should be clear to slightly opalescent, colorless to brownish-yellow and free of visible particles.
Discard any vial with visible particles or discoloration. 5. Based upon the calculated dose amount, the reconstituted solution from the vial(s) should be added to the infusion bag immediately. This product does not contain a preservative. If not used immediately, reconstituted vials may be stored for up to 24 hours in refrigeration at 2°C to 8°C (36 °F to 46 °F) or at room temperature up to 25°C (77°F) for up to a maximum of 8 hours prior to dilution.
DO NOT FREEZE. Do not expose to direct sunlight. Discard unused vials with reconstituted solution beyond the recommended storage time. Dilution in Infusion Bag 1. Withdraw the calculated dose amount of reconstituted solution from the vial(s) and transfer into an infusion bag. 2. Dilute TIVDAK with one of the following: 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP or Lactated Ringer's Injection, USP.
The infusion bag size should allow enough diluent to achieve a final concentration of 0.7 mg/mL to 2.4 mg/mL TIVDAK. 3. Mix diluted solution by gentle inversion. DO NOT SHAKE THE BAG. Do not expose to direct sunlight. 4. Visually inspect the infusion bag for any particulate matter or discoloration prior to use. The reconstituted solution should be clear to slightly opalescent, colorless to brownish-yellow and free of visible particles.
Discard the infusion bag if particulate matter or discoloration is observed. 5. Discard any unused portion left in the single-dose vials. Administration 1. Confirm administration of steroid and vasoconstrictor eye drops [see Dosage and Administration ]. 2. Apply cold packs fully over the eyes following administration of the vasoconstrictor eye drops.
Change cold packs as needed throughout infusion to ensure eye area remains cold during the entire infusion [see Dosage and Administration ]. 3. Immediately administer the infusion over 30 minutes through an intravenous line containing a 0.2 µm in-line filter. 4. If the infusion is not administered immediately, store the diluted TIVDAK solution in refrigeration as specified in Table 3 .
Discard if storage time exceeds these limits. DO NOT FREEZE. Once removed from refrigeration, complete administration of the diluted infusion solution of TIVDAK within 4 hours (including infusion time). [See table below.]
| Diluent Used to Prepare Solution for Infusion | Diluted TIVDAK Solution Storage Conditions (Including Infusion Time) |
| 5% Dextrose Injection, USP | Up to 24 hours at 2°C to 8°C (36°F to 46°F) |
| 0.9% Sodium Chloride Injection, USP | Up to 18 hours at 2°C to 8°C (36°F to 46°F) |
| Lactated Ringer’s Injection, USP | Up to 12 hours at 2°C to 8°C (36°F to 46°F) |
Drug interactions
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Add the patient's other drugs. Matches come from both FDA labels: by name, drug class, and enzyme or transporter pathway.
- Tisotumab vedotin
Label text (2 paragraphs)
Strong CYP3A4 Inhibitors: Closely monitor for TIVDAK adverse reactions. ( 7.1 )
7.1 Effects of Other Drugs on TIVDAK Strong CYP3A4 Inhibitors MMAE is a CYP3A4 substrate. Concomitant use of TIVDAK with strong CYP3A4 inhibitors may increase unconjugated MMAE exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for adverse reactions of TIVDAK when used concomitantly with strong CYP3A4 inhibitors.
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
ELikelihood score E: Unlikely cause of clinically significant liver injury.
Tisotumab vedotin is a human monoclonal antibody conjugate which is used in the therapy of refractory, recurrent or metastatic cervical cancer. Tisotumab vedotin has been linked to transient mild-to-moderate serum aminotransferase elevations during therapy but has not been implicated in cases of liver injury with jaundice.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on the mechanism of action and findings in animals, TIVDAK can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available human data on TIVDAK use in pregnant women to inform a drug-associated risk. In an animal reproduction study, administration of the small molecule component of TIVDAK, MMAE, to pregnant rats during organogenesis caused embryo-fetal mortality and structural abnormalities at exposures below the clinical exposure at the recommended dose (see Data ) . Advise patients of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data No embryo-fetal development studies in animals have been performed with tisotumab vedotin-tftv.
In an embryo-fetal development study in pregnant rats, administration of two intravenous doses of MMAE, the small molecule component of TIVDAK, on gestational days 6 and 13 caused embryo-fetal mortality and structural abnormalities, including protruding tongue, malrotated limbs, gastroschisis, and agnathia compared to controls at a dose of 0.2 mg/kg (approximately 0.5-fold the human area under the curve [AUC] at the recommended dose).
Breastfeeding (LactMed)
No information is available on the clinical use of tisotumab vedotin during breastfeeding. Because tisotumab is a large protein molecule with a molecular weight of about 153,000 Da, the amount in milk is likely to be very low. It is also likely to be partially destroyed in the infant's gastrointestinal tract and absorption by the infant is probably minimal. Vedotin (monomethyl auristatin E) is a small-molecule anticancer drug that might enter milk and be absorbed by the infant. Because of the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends that breastfeeding be discontinued during enfortumab vedotin therapy and for 3 weeks after the last dose.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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