ANKTIVA Concentrate for intravesical suspension Ref.[116339] Active ingredients: Nogapendekin alfa

Posology

Induction therapy

ANKTIVA is recommended at a dose of 400 micrograms; administered intravesically as a mixture with BCG recommended at a dose of 50 mL once a week for 6 weeks. A second induction course (re-induction) may be administered in case of residual CIS +/- High grade Ta at the first assessment after induction (at week 12) (see section 4.4. concerning the re-consideration of cystectomy in patients with residual disease). See section 5.1 for pharmacodynamic properties.

Maintenance therapy

After BCG and ANKTIVA induction therapy, for patients with lack of disease or low-grade Ta, continued treatment is recommended at a dose of 400 micrograms administered intravesically with BCG once a week for 3 consecutive weeks at months 4, 7, 10, 13 and 19 (for a total of 15 doses).

Presence of a low-grade Ta will require a transurethral resection of bladder tumour (TURBT) procedure prior to instillation. Treatment may be delayed by up to 28 days after TURBT procedure if required. For patients with an ongoing complete response as defined by negative results for cystoscopy [with TURBT/biopsies as applicable] and urine cytology at month 25 and later, maintenance instillations with ANKTIVA and BCG may be administered once a week for 3 consecutive weeks at months 25, 31, and 37 for a maximum of 9 additional instillations. Assessment of tumour status should be performed every 3 months for up to 24 months. Assessment for ongoing response beyond month 24 is per local community standards.

The recommended duration of treatment is until disease persistence after the last induction cycle (initial, or if administered, second induction) disease recurrence or progression (new CIS and/or any T1 disease or greater), unacceptable toxicity, or a maximum treatment duration of 37 months.

Special populations

Elderly

No dose adjustments are necessary in the elderly population.

Hepatic and/or renal impairment

No dose adjustments are necessary in patients with hepatic and/or renal impairment.

Paediatric population

There is no relevant use of ANKTIVA in the paediatric population in children aged 0 to less than 18 years in the indication BCG-unresponsive NMIBC CIS with or without papillary tumours.

Method of administration

For intravesical use.

Do not shake.

For instructions on dilution of the medicinal product before intravesical administration, see section 6.6.

ANKTIVA is administered intravesically with BCG into the bladder via a catheter. Connect a catheter to the suspension container directly or using a 50-mL syringe connected to an appropriate size needle/connecter, withdraw the 50 mL ANKTIVA with BCG mixture and attach to a urinary catheter. Instil the mixture through the urinary catheter and into the bladder.

After instillation is complete, the catheter is removed. The ANKTIVA in combination with BCG admixture is retained in the bladder for 2 hours and then voided. Patients unable to retain the suspension for 2 hours should be allowed to void sooner, if necessary. The dose should not be repeated if the patient voids before 2 hours.

See BCG Summary of Product Characteristics for information on retention in the bladder and patient positioning during bladder instillation.

There are no data indicating that an overdose may lead to any other symptoms than the described undesirable effects. In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted.

3 years.

Chemical and physical in‑use stability of the admixture of ANKTIVA with:

• OncoTICE has been demonstrated for up to 2 hours at 2°C to 8°C, protected from light.
• BCG‑medac has been demonstrated for up to 24 hours at 2°C to 8°C, protected from light.

ANKTIVA has only been studied with OncoTICE and BCG-medac.

From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Store in a refrigerator (2°C - 8°C).

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

0.4 mL solution in a glass vial with a serum stopper (chlorobutyl elastomer with a Flurotec B2-40 coating) and an aluminium alloy seal containing a yellow plastic polypropylene flip-off cap.

Pack size: 1 single-dose vial.

Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard the vial if visible particles are observed.

Prepare a suspension of BCG according to the instructions provided in the manufacturer's Summary of Product Characteristics for the specific BCG being used. Only OncoTICE and BCG-medac should be used.

Obtain a vial of ANKTIVA (do not shake), remove the flip-off cap and disinfect the stopper. Withdraw 0.4 mL of ANKTIVA using a sterile needle and syringe (1-3 mL). Using clean technique, promptly add ANKTIVA to the sodium chloride solution containing the BCG suspension utilizing appropriate connectors and/or septum (as needed), depending on the saline container used for the BCG suspension. Mix the suspension gently.

Any spilled ANKTIVA BCG mixture should be cleaned by covering the area with paper towels soaked with tuberculocidal disinfectant for at least 10 minutes. Unused ANKTIVA with BCG and all equipment, supplies, and receptacles in contact with it should be handled and disposed of as biohazardous.

Accidental exposure to ANKTIVA BCG mixture could occur through self-inoculation, by dermal exposure through an open wound or by ingestion of ANKTIVA with BCG. Exposure should not produce significant adverse health outcomes in healthy individuals. However, in case of suspected, accidental self-inoculation, PPD skin testing is advised at the time of the accident and six weeks later to detect skin test conversion.

Precautions to be taken before handling or administering the medicinal product

Standard precautions of personal protective equipment are the same as BCG. No precautions are needed for ANKTIVA in addition to the BCG precautions.