TIVDAK Solution for injection Ref.[109850] Active ingredients: Tisotumab vedotin

2.1 Recommended Dosage

The recommended dose of TIVDAK 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.

2.2 Premedication and Required Eye Care

Adhere to the following recommendations to reduce the risk of ocular adverse reactions [see Warnings and Precautions (5.1)].

• Ophthalmic exam by eye care provider: Conduct an ophthalmic exam prior to initiation of TIVDAK, 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 TIVDAK.
• Cold packs: Use cooling eye pads during each infusion of TIVDAK.
• Topical lubricating eye drops: Instruct patients to administer for the duration of therapy and for 30 days after the last dose of TIVDAK.
• Contact lenses: Advise patients to avoid wearing contact lenses for the entire duration of therapy unless advised by their eye care provider.

2.3 Dosage Modifications for Adverse Reactions

The recommended TIVDAK dose reduction schedule is provided in Table 1.

Table 1. Dosage Reduction Schedule:

^* 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:

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

2.4 Instructions for Preparation and Administration

• Administer TIVDAK as an intravenous infusion only.
• TIVDAK is a hazardous drug. Follow applicable special handling and disposal procedures¹.
• 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 (2.2)].

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 (2.2)].

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).

Table 3. Diluted TIVDAK Solution Refrigeration Storage Conditions:

Storage:

Store TIVDAK vials refrigerated at 2ºC to 8ºC (36ºF to 46ºF) in the original carton to protect from light. Do not freeze. Do not shake.

Special Handling:

TIVDAK is a hazardous drug. Follow special handling and disposal procedures.¹