KEYTRUDA Powder for solution for infusion Ref.[7435] Active ingredients: Pembrolizumab

Therapy must be initiated and supervised by specialist physicians experienced in the treatment of cancer.

PD-L1 testing for patients with NSCLC, urothelial carcinoma, or HNSCC

Testing for PD-L1 tumour expression using a validated test is recommended for patients with NSCLC. In patients with NSCLC whose tumours have high PD-L1 expression, the risk of adverse reactions with combination therapy relative to pembrolizumab monotherapy should be considered and the benefit/risk ratio of the combined therapy evaluated on an individual basis (see sections 4.1, 4.4, 4.8 and 5.1).

Patients with previously untreated urothelial carcinoma or HNSCC should be selected for treatment based on the tumour expression of PD-L1 confirmed by a validated test (see section 5.1).

Posology

The recommended dose of KEYTRUDA as monotherapy is either 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes.

The recommended dose of KEYTRUDA as part of combination therapy is 200 mg every 3 weeks administered as an intravenous infusion over 30 minutes.

Patients should be treated with KEYTRUDA until disease progression or unacceptable toxicity. Atypical responses (i.e. an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed.

For the adjuvant treatment of melanoma, KEYTRUDA should be administered until disease recurrence, unacceptable toxicity, or for a duration of up to one year.

Dose delay or discontinuation (see also section 4.4)

Table 1. Recommended treatment modifications for KEYTRUDA:

The safety of re-initiating pembrolizumab therapy in patients previously experiencing immune-related myocarditis is not known.

KEYTRUDA should be permanently discontinued for Grade 4 or recurrent Grade 3 adverse reactions, unless otherwise specified in Table 1.

For Grade 4 haematological toxicity, only in patients with cHL, KEYTRUDA should be withheld until adverse reactions recover to Grade 0-1.

Patients treated with KEYTRUDA must be given the Patient Alert Card and be informed about the risks of KEYTRUDA (see also package leaflet).

Special populations

Elderly

No dose adjustment is necessary in patients ≥65 years (see section 5.1). Data from patients ≥65 years are too limited to draw conclusions on cHL population (see section 5.1). Data from pembrolizumab monotherapy in patients with resected Stage III melanoma and from chemotherapy combination in patients with metastatic NSCLC ≥75 years are limited (see sections 4.4 and 5.1).

Renal impairment

No dose adjustment is needed for patients with mild or moderate renal impairment. KEYTRUDA has not been studied in patients with severe renal impairment (see sections 4.4 and 5.2).

Hepatic impairment

No dose adjustment is needed for patients with mild hepatic impairment. KEYTRUDA has not been studied in patients with moderate or severe hepatic impairment (see sections 4.4 and 5.2).

Ocular melanoma

There are limited data on the safety and efficacy of KEYTRUDA in patients with ocular melanoma (see section 5.1).

Eastern Cooperative Oncology Group (ECOG) performance status score ≥2

Patients with ECOG performance status score ≥2 were excluded from the clinical trials of melanoma, NSCLC, cHL, and HNSCC (see sections 4.4 and 5.1).

Paediatric population

The safety and efficacy of KEYTRUDA in children below 18 years of age have not yet been established. Currently available data are described in sections 4.8, 5.1 and 5.2.

Method of administration

KEYTRUDA must be administered by intravenous infusion over 30 minutes. KEYTRUDA must not be administered as an intravenous push or bolus injection.

When administering KEYTRUDA as part of a combination with chemotherapy, KEYTRUDA should be administered first. See also the prescribing information for the chemotherapy agents administered in combination.

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

There is no information on overdose with pembrolizumab.

In case of overdose, patients must be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted.

Shelf life

Unopened vial: 3 years.

After reconstitution: From a microbiological point of view, the reconstituted or diluted solution should be used immediately. The reconstituted or diluted solution must not be frozen. If not used immediately, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 24 hours at 2°C to 8°C. This 24 hour total hold from reconstitution may include up to 6 hours at room temperature (at or below 25°C). If refrigerated, the vials and/or intravenous bags must be allowed to come to room temperature prior to use.

Store in a refrigerator (2°C–8°C).

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

15 mL Type I glass vial, with a grey bromobutyl stopper and an aluminium seal with an avocado coloured flip-off cap, containing 50 mg pembrolizumab.

Each carton contains one vial.

Preparation and administration:

• Prior to reconstitution, the vial of lyophilised powder can be out of refrigeration (temperatures at or below 25°C) for up to 24 hours.
• Aseptically add 2.3 mL of water for injections to yield a 25 mg/mL (pH 5.2-5.8) solution of KEYTRUDA. Each vial contains an excess fill of 10 mg (0.4 mL) to ensure the recovery of 50 mg of KEYTRUDA per vial. After reconstitution, 1 mL of concentrate contains 25 mg of pembrolizumab.
• To avoid foaming, deliver the water along the walls of the vial and not directly on the lyophilised powder.
• Slowly swirl the vial to allow reconstitution of the lyophilised powder. Allow up to 5 minutes for the bubbles to clear. Do not shake the vial.
• Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration. Reconstituted KEYTRUDA is a clear to slightly opalescent, colourless to slightly yellow solution. Discard the vial if visible particles are observed.
• Withdraw the required volume up to 2 mL (50 mg) of KEYTRUDA and transfer into an intravenous bag containing sodium chloride 9 mg/mL (0.9%) or glucose 50 mg/mL (5%) to prepare a diluted solution with a final concentration ranging from 1 to 10 mg/mL. Mix diluted solution by gentle inversion.
• From a microbiological point of view, the reconstituted or diluted solution should be used immediately. The reconstituted or diluted solution must not be frozen. If not used immediately, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 24 hours at 2°C to 8°C. This 24 hour total hold from reconstitution may include up to 6 hours at room temperature (at or below 25°C). If refrigerated, the vials and/or intravenous bags must be allowed to come to room temperature prior to use. Administer the infusion solution intravenously over 30 minutes using a sterile, non-pyrogenic, low-protein binding 0.2 to 5 μm in-line or add-on filter.
• Do not co-administer other medicinal products through the same infusion line.
• KEYTRUDA is for single use only. Discard any unused portion left in the vial.

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