IMJUDO Concentrate for solution for infusion Ref.[50776] Active ingredients: Tremelimumab

Treatment must be initiated and supervised by a physician experienced in the treatment of cancer.

Posology

The recommended dose of IMJUDO is presented in Table 1. IMJUDO is administered as an intravenous infusion over 1 hour.

Table 1. Recommended dose of IMJUDO:

^a For IMJUDO, HCC patients with a body weight of 40 kg or less must receive weight-based dosing, equivalent to IMJUDO 4 mg/kg until weight is greater than 40 kg. For durvalumab, patients with a body weight of 30 kg or less must receive weight-based dosing, equivalent to durvalumab 20 mg/kg until weight is greater than 30 kg.

Dose escalation or reduction is not recommended during treatment with IMJUDO in combination with durvalumab. Treatment withholding or discontinuation may be required based on individual safety and tolerability.

Guidelines for management of immune-mediated adverse reactions are described in Table 2 (see section 4.4). Refer also to the summary of product characteristics (SmPC) for durvalumab.

Table 2. Treatment modifications and management recommendations for IMJUDO in combination with durvalumab:

^a Common Terminology Criteria for Adverse Events, version 4.03. ALT: alanine aminotransferase; AST: aspartate aminotransferase; ULN: upper limit of normal; BLV: baseline value.
^b Upon improvement to ≤ Grade 1, corticosteroid taper should be initiated and continued over at least 1 month.
Consider increasing dose of corticosteroids and/or using additional systemic immunosuppressants if there is worsening or no improvement.
^c After withholding, IMJUDO and/or durvalumab can be resumed within 12 weeks if the adverse reactions improved to ≤ Grade 1 and the corticosteroid dose has been reduced to ≤10 mg prednisone or equivalent per day. IMJUDO and durvalumab should be permanently discontinued for recurrent Grade 3 adverse reactions, as applicable.
^d For patients with alternative cause follow the recommendations for AST or ALT increases without concurrent bilirubin elevations.
^e If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue durvalumab based on recommendations for hepatitis with no liver involvement.
^f If no improvement within 2 to 3 days despite corticosteroids, promptly start additional immunosuppressive therapy. Upon resolution (Grade 0), corticosteroid taper should be initiated and continued over at least 1 month.
^g Permanently discontinue IMJUDO and durvalumab if the adverse reaction does not resolve to ≤ Grade 1 within 30 days or if there are signs of respiratory insufficiency.
^h Includes immune thrombocytopenia and pancreatitis.
ⁱ With the exception of Grade 4 laboratory abnormalities, about which the decision to discontinue treatment should be based on accompanying clinical signs/symptoms and clinical judgment.

For suspected immune-mediated adverse reactions, adequate evaluation should be performed to confirm aetiology or exclude alternate aetiologies.

Special populations

Paediatric population

The safety and efficacy of IMJUDO in children and adolescents below 18 years of age have not been established. No data are available.

Elderly

No dose adjustment is required for elderly patients (≥65 years of age) (see section 5.2).

Renal impairment

No dose adjustment of IMJUDO is recommended in patients with mild or moderate renal impairment. Data from patients with severe renal impairment are too limited to draw conclusions on this population (see section 5.2).

Hepatic impairment

No dose adjustment of IMJUDO is recommended for patients with mild or moderate hepatic impairment. IMJUDO has not been studied in patients with severe hepatic impairment (see section 5.2).

Method of administration

IMJUDO is for intravenous use.

Administer IMJUDO prior to durvalumab on the same day.

IMJUDO and durvalumab are administered as separate intravenous infusions. Refer to the SmPC for durvalumab administration information.

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

There is no information on overdose with tremelimumab. In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted immediately.

Unopened vial:

4 years at 2°C-8°C.

Diluted solution:

Chemical and physical in-use stability has been demonstrated for up to 28 days at 2°C to 8°C and for up to 48 hours at room temperature (up to 25°C) from the time of preparation.

From a microbiological point of view, the prepared solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C or 12 hours at room temperature (up to 25°C), unless dilution has taken place in controlled and validated aseptic conditions.

Lack of microbial growth in the prepared solution for infusion has been demonstrated for up to 28 days at 2°C to 8°C and for up to 48 hours at room temperature (up to 25°C) from the time of preparation.

Store in a refrigerator (2°C-8°C).

Do not freeze.

Store in the original package in order to protect from light.

For storage conditions after dilution of the medicinal product, see section 6.3.

Two pack sizes of IMJUDO are available:

• 1.25 ml (a total of 25 mg tremelimumab) concentrate in a Type I glass vial with an elastomeric stopper and a violet flip-off aluminum seal. Pack size of 1 single-dose vial.
• 15 ml (a total of 300 mg tremelimumab) concentrate in a Type I glass vial with an elastomeric stopper and a dark blue flip-off aluminum seal. Pack size of 1 single-dose vial.

Not all pack sizes may be marketed.

Preparation of solution:

IMJUDO is supplied as a single-dose vial and does not contain any preservatives, aseptic technique must be observed.

• Visually inspect medicinal product for particulate matter and discolouration. IMJUDO is clear to slightly opalescent, colourless to slightly yellow solution. Discard the vial if the solution is cloudy, discoloured or visible particles are observed. Do not shake the vial.
• Withdraw the required volume from the vial(s) of IMJUDO and transfer into an intravenous bag containing sodium chloride 9 mg/ml (0.9%) solution for injection, or glucose 50 mg/ml (5%) solution for injection. Mix diluted solution by gentle inversion. The final concentration of the diluted solution should be between 0.1 mg/ ml and 10 mg/ml. Do not freeze or shake the solution.
• Care must be taken to ensure the sterility of the prepared solution.
• Do not re-enter the vial after withdrawal of the medicinal product.
• Discard any unused portion left in the vial.

Administration:

• Administer the infusion solution intravenously over 60 minutes through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter.
• Do not co-administer other medicinal products through the same infusion line.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.