Lumoxiti - summary of medicine characteristics

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One vial of powder for concentrate contains 1 mg moxetumomab pasudotox.

Reconstitution with water for injections results in a final moxetumomab pasudotox vial of 1 mg/mL.

Moxetumomab pasudotox is produced in Escherichia coli cells by recombin

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder for concentrate and solution for solution for infusio

Powder for concentrate: white to off-white

Solution (stabiliser): colourless-to-slightly yellow, clear solution with a pH of 6.0.

4.1 Therapeutic indications

4.2 Posology

be initiated and supervised by a physician experienced in the use of anticancer ts.

Posology

The recommended dose of Lumoxiti is 0.04 mg/kg administered as a 30-minute intravenous infusion on Days 1, 3, and 5 of each 28-day cycle. Patients should continue treatment for a maximum of 6 cycles, or until disease progression or unacceptable toxicity. Treatment may be stopped at the physician’s dis­cretion if complete response (CR) without minimal residual disease (MRD) is achieved prior to the completion of 6 cycles.

Hydration

In patients over 50 kg, 1 L isotonic solution (e.g. dextrose 50 mg/mL [5%] and sodium chloride

9 mg/mL [0.9%] or 4.5 mg/mL [0.45%] solution for injection) should be administered intravenously over 2–4 hours before and after each Lumoxiti infusion. Patients under 50 kg require 0.5 L to be administered.

Patients should be adequately hydrated. Patients are advised to drink 3 L of oral fluids per 24 hours on Days 1 through 8 of each 28-day cycle. In patients under 50 kg, 2 L per day is recommended.

Fluid balance should be monitored to avoid fluid overload (see section 4.4).

Premedication

Premedication is required 30–90 minutes prior to each Lumoxiti infusion with an oral antihistamine (e.g. hydroxyzine or diphenhydramine), an antipyretic (e.g. paracetamol), and a histamine-2 receptor antagonist (e.g. ranitidine, famotidine, or cimetidine).

If a severe infusion related reaction occurs, see section 4.4 for further instructions.

Dose adjustments

Lumoxiti treatment must be withheld and/or discontinued to manage adverse reactions as de below.                                                                          ♦ e.

Haemolytic uraemic syndrome (HUS) and capillary leak syndrome (CLS) are identified clinical presentation (see Table 1).

Table 1 Monitoring for HUS and CLS

Before every infusion, check:

Table 2 HUS grading and management guidance

Special populations

Elderly

No dose adjustment is required for elderly patients (>65 years of age) (see Renal function monitoring in section 4.4, and Elderly in sections 4.8 and 5.1).

Renal impairment

No dose adjustment of Lumoxiti is recommended for patients with mild renal impairment. Data supporting use of moxetumomab pasudotox in moderate renal impairment is limited. Moxetumomab pasudotox has not been studied in patients with severe renal impairment (see Renal function monitoring in section 4.4).

Hepatic impairment

No dose adjustment of Lumoxiti is recommended for patients with mild hepatic impairment.

Moxetumomab pasudotox has not been studied in patients with moderate or severe hepatic impairment (see section 5.2).

Paediatric population

There is no relevant use of Lumoxiti in children aged 0 to 18 years in the treatment of HCL.

Method of administration

Lumoxiti is for intravenous use.

The diluted solution is administered intravenously over 30 minutes. An infusion set fitte sterile, low-protein binding 0.22 micron in-line filter should be used.

After the infusion, the intravenous administration line should be flushed with sodium

9 mg/mL (0.9%) solution for injection at the same rate as the infusion. This ensures the full Lumoxiti dose is delivered.

For instructions on reconstitution and dilution of the medicinal section 6.6.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the exci

4.4 Special warnings and precautions for use

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number

of the administered product should be clea

Haemolytic uraemic syndrome (HU;

HUS has been reported in patients treated with Lumoxiti and is characterized by the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and progressive renal failure (see section 4.8).

Lumoxiti should be avoided in patients with prior history of severe thrombotic microangiopathy (TMA) or HUS. Prophylactic fluids are recommended during treatment with Lumoxiti (see section 4.2). In Study 1053, patients with a platelet count >100,000/mm3 received low-dose acetylsalicylic acid on Dayhrough 8 of each 28-day cycle for prophylaxis of renal insufficiency.

and complete blood counts should be monitored prior to each dose and as clinically ring treatment. Monitoring mid-cycle is also recommended. Diagnosis of HUS should be ed in patients who develop haemolytic anaemia, worsening or sudden onset of thrombocytopenia, worsening of renal function, elevation of bilirubin and/or LDH, and have evidence of haemolysis based on peripheral blood smear schistocytes (see section 4.2).

The events of HUS may be life-threatening if treatment is delayed with increased risk of progressive renal failure requiring dialysis. If HUS is suspected appropriate supportive measures including fluid repletion and haemodynamic monitoring should be initiated, and hospitalisation as clinically indicated should be considered. For Grade 2 HUS, treatment with Lumoxiti should be withheld until resolution, and permanently discontinued for Grade >3 HUS (see section 4.2).

Capillary leak syndrome (CLS)

Women of childbearing potential/con­traception

Women of childbearing potential should use effective contraception during treatment with moxetumomab pasudotox and for at least 30 days after the last dose.

Pregnancy

There are no human or animal data to assess the risk of moxetumomab pasudotox use during pregnancy. Based on its mechanism of action and observed adverse findings of moxetumomab pasudotox in non-pregnant female monkeys including body weight loss, moxetumomab pasudotox may be expected to cause maternal and embryofetal toxicity when administered to a pregnant woman. Moxetumomab pasudotox should not be used during pregnancy unless the potential benefit outweighs the potential risk to the foetus.

Breast-feeding

There is no information regarding the presence of moxetumomab pasudotox in human milk, the absorption and effects on the breast-fed child, or the effects on milk production. A risk to the breast-fed child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue Lumoxiti therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

No adverse findings of moxetumomab pasudotox were observed on reproductive organ weights or reproductive organ histopathology following dosing of sexually mature monkeys. There are no data available to directly determine the potential effects on human fertility (see section 5.3).

4.7 Effects on ability to drive and use machines

Lumoxiti has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Summary of the safety profile

The overall safety profile of Lumoxiti is based on data from 80 patients from Study 1053 (a Phase 3 study).

The most common adverse drug reactions (ADRs) (>20%) of any grade were oedema (52.5%), nausea (35.0%), infusion related reactions (25.0%), hypoalbuminemia (21.3%), and increased transaminases (21.3%). The most common Grade 3 or 4 ADR was HUS (6.3%).

Adverse reactions resulting in permanent discontinuation of Lumoxiti occurred in 10.0% of patients. The most common adverse reaction leading to Lumoxiti discontinuation was HUS (5.0%). The adverse reaction that most commonly resulted in dose delays was increased serum creatinine (2.5%).

Tabulated list of adverse reactions

ADRs are listed according to system organ class (SOC) in MedDRA. Within each SOC, the ADRs are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, ADRs are presented in order of decreasing seriousness. Frequency category for each ADR is defined as: very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100); rare (>1/10,000 to <1/1000); very rare (<1/10,000); not known (cannot be estimated from available data).

Table 4 Adverse drug reactions in patients with HCL treated with Lumoxiti (n=80)

a Hypoalbuminaemia: includes preferred terms (PTs) of ‘hypoalbuminaemia’ and ‘blood albumin decreased’ b Oedema: includes all PTs of ‘oedema peripheral,’ ‘oedema,’ ‘localized oedema,’ ‘face oedema,’ ‘periorbita oedema,’ and ‘peripheral swelling’

c Transaminases increased: includes ‘aspartate aminotransferase increased’ and/or ‘alanine aminotransferase increased’

d Infusion related reactions: includes all events regardless of relatedness, as reported by investigator or as retrospectively defined by co-occurrence of 2 or more events of headache, dizziness, hypotension, myalgia, pyrexia, chills, nausea, and/or vomiting on the day of study drug infusion

Description of selected adverse reactions

HUS

In Study 1053 in patients with HCL treated with Lumoxiti, HUS occurred in 8.8% of patients, including Grade 3 in 5.0% and Grade 4 in 1.3%.

The median time to first onset of HUS was 33 days (range: 9–92), and may occur during any cyc treatment with Lumoxiti. Most cases of HUS occurred in the first 9 days (range: 1–16) of a treat cycle. The median time to resolution of HUS was 23.5 days (range: 2–44). All cases resolved, including those who discontinued Lumoxiti.                                     ­♦ cc-

The median end of treatment creatinine clearance (as estimated by Cockcroft-Gault) among patients without HUS (89 mL/min, range 42–195) compared with patien (76 mL/min, range 19–96).

For clinical management of HUS, see section 4.4.

CLS

In Study 1053 in patients with HCL treated with Lumoxiti, CL majority were Grade 2. There were 2.5% Grade 4 events.

The median time to onset of CLS was 37 days (range: 5–92), and may occur during any cycle of treatment. Most cases of CLS occurred in the first 9 days (range: 1–24) of a treatment cycle. All CLS resolved, with a median time to resolution of 36 days (range: 10–53).

For clinical management of CLS, see section 4.4.

Increase in serum creatinine

In Study 1053, increases in creatinine up to a maximum of 3-times the upper limit of normal were reported in 11.3% of patients. At the end of treatment, serum creatinine levels were within normal limits for the majority (82.5%) of patients. Serum creatinine levels remained elevated above Grade 2 in 5% of patients, two of these patients had Grade 3 or 4 HUS.

Infusion related reactions

Infusion-related reactions as reported by investigator or retrospectively defined as two or more symptoms of headache, dizziness, hypotension, myalgia, pyrexia, chills, nausea, and/or vomiting on the day of treatment with study drug occurred in 25% of patients, including Grade 3 in 2.5% of patients. Infusion related reactions may occur during any cycle of treatment with Lumoxiti (see section 4.2).

Special populations

Elderly

In Study 1053, 39% of patients treated with Lumoxiti were 65 years of age or older. Patients >65 years of age had lower median creatinine clearance at baseline and at the end of treatment compared with patients <65 years of age (78 and 69 mL/min versus 114 and 98 mL/min, respectively).

Immunogenicity

In Study 1053, 88% (70/80) of patients were positive for ADA (before or after treatment). Fifty-eight percent (45/77) of patients tested positive for anti-drug antibodies (ADAs) prior to any treatment with moxetumomab pasudotox, and 66% (49/74) of patients tested positive for ADAs whilst on treatment.

Neutralising antibodies against moxetumomab pasudotox were detected in 84% of patients (67/80) at any time. No clinically relevant effects of ADA on safety were identified. See Immunogenicity in section 5.2.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in.

4.9 Overdose

5.  PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: antineoplastic agents, other antineoplastic agents, ATC code: L01XC34

Mechanism of action

Moxetumomab pasudotox is a CD22-targeted immunotoxin designed to direct the cytotoxic action of the truncated Pseudomonas exotoxin to cells which express the CD22 receptor. CD22 is a B-lymphocyte restricted transmembrane protein with a similar or higher receptor density in HCL cells relative to normal B cells. Nonclinical data indicate that the anticancer activity of moxetumomab pasudotox is due to the binding of the immunotoxin to CD22-expressing tumour cells, followed by internalisation of the Lumoxiti-CD22 complex and processing to release the active PE38 exotoxin. The exotoxin is translocated to the cytosol where it inactivates elongation factor 2 (EF-2), causing inhibition of protein synthesis leading to apoptotic cell death.

Pharmacodynamic effects

In patients with HCL, treatment with Lumoxiti resulted in a reduction of circulating CD19+ B cells. In Study 1053, circulating CD19+ B cells were reduced by 89% from baseline following the first three infusions of Lumoxiti. This reduction was sustained for at least one month post-treatment.

Clinical efficacy and safety

The efficacy and safety of Lumoxiti were evaluated in Study 1053, a multicentre, single-arm, Phase 3 study in patients with relapsed/refractory HCL. Study 1053 was conducted in patients with histologically confirmed HCL or HCL variant who had received prior treatment with at least 2 systemic therapies, including 1 PNA, with a need for therapy based on at least one of the following criteria: neutrophils <1.0 × 109/L, platelets <100 × 109/L, haemoglobin <10 g/dL or symptomatic splenomegaly.

The study excluded patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks of treatment initiation, patients with history of allogeneic bone marrow transplant, patients with known brain metastases, retinal or choroidal detachment, or uncontrolled illness including uncontrolled infection. Further exclusion criteria were a history of thromboembolism, known congenital hypercoagulable conditions, thrombotic microangiopathy/HUS or clinical evidence of severe disseminated intravascular coagulation.

A total of 80 patients were enrolled; 77 with classic HCL and 3 with HCL variant. The median age was 60 (range 34 to 84) years, 79% were male, and 94% were Caucasian at primary analysis. At baseline, 98% of patients had an ECOG performance status of 0 or 1. The median number of prior treatments was 3 (range 2 to 11); all patients received prior PNA therapy, including 29% in combination with rituximab. The most common other prior treatment regimens were rituximab monotherapy (51%), interferon-alpha (25%), and a BRAF inhibitor (18%). At baseline, 33% (26/80) of patients had low haemoglobin (<10 g/dl), 68% (54/80) of patients had neutropenia (<1.0 × 109/L), and 84% (67/80) of patients had baseline platelet counts <100 × 109/L. Almost half (48%) of the patients had enlarged spleens at baseline. During screening, 23.8% of patients had an ongoing infection which was adequately controlled or resolved prior to treatment initiation.

Patients received Lumoxiti 0.04 mg/kg as an intravenous infusion over 30 minutes on Days 1, 3, and 5 of each 28-day cycle for a maximum of 6 cycles or until documentation of complete response (CR), disease progression, initiation of alternate therapy, or unacceptable toxicity. Approximately 63% of patients completed 6 cycles and 15% of patients completed treatment earlier than 6 cycles with documentation of minimal residual disease (MRD)-negative CR. An independent review committee (IRC) performed efficacy evaluations using blood, bone marrow, and imaging criteria adapted from previous HCL studies and consensus guidelines.

er

The major efficacy outcome of Study 1053 was durable CR, as confirmed by maintenance of haematologic remission (haemoglobin >11.0 g/dL, neutrophils >1.5 × 109/L, and platelets >100 × 109/L without transfusions or growth factor for at least 4 weeks) more than 180 days after IRC-assessed CR.

At the time of final analysis (cut-off date of 29 April 2019), the median follow-up was 24.6 months (range 1 to 72). The efficacy results from Study 1053 are summarised in Table 5.

Table 5 Efficacy results in patients with HCL in study 10

IRC = Independent Review Committee-Assessed; HR = Haematologic Remission; CI = Confidence Interval; CR = Complete Response; OR = Overall Response.

a CR defined as clearing of the bone marrow of hairy cells by routine Haematoxylin & Eosin stain, radiologic resolution of pre-existing lymphadenopathy and/or organomegaly, and haematologic remission

b PR defined as > 50% decrease or normalisation (<500/mm3) in peripheral blood lymphocyte count, reduction of pre-existing lymphadenopathy and/or organomegaly, and haematologic remission.

c SD defined as > 50% decrease of peripheral blood lymphocyte count, reduction of pre-existing lymphadenopathy and/or organomegaly, and haematologic remission or 50% improvement over baseline for haematologic parameters if not meeting haematologic remission criteria.

MRD was evaluated by IRC via immunohistoche­mistry assessment of bone marrow biopsies. At the time of the final analysis, of the 33 patients who achieved IRC-assessed CR, 82% (27/33) were

MRD-negative and 26 of the 29 patients (89.7%) who achieved a durable CR were MRD-negative. The median duration of CR was 12.0 months for MRD-positive patients (n = 6) and 62.8 months for MRD-negative patients (n = 27).

Pre-specified sub-group analyses of primary and secondary endpoints were performed for the ITT population including age (<65 years, >65 years), gender, baseline spleen status (splenectomy, <14 cm, >14 cm), number of prior treatments with PNA (1, 2, >2) and HCL histology (classic, variant). The analyses showed that the effect on durable CR rate and CR rate across the majority of sub-groups evaluated were consistent with the results for the ITT population. For subjects >65 years, the durable CR rate was 19% (95% CI: 8%, 38%) and the CR rate assessed by IRC was 26% (95% CI: 12%, 47%). Data are limited for the splenectomy and HCL variant subgroups. No CRs were reported; 2 of 4 patients in the splenectomy subgroup and 1 of 3 patients in the HCL variant subgroup achieved

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studi Lumoxiti in all subsets of the paediatric population in HCL (see section 4.2 for paediatric use).

Other information

This medicinal product has been authorised under ‘exceptional circumstanc      is means that due to

the rarity of the disease it has not been possible to obtain complete information on this medicinal product. The European Medicines Agency will review any new information which may become available every year and this SmPC will be updated as necessary.

5.2 Pharmacokinetic properties

The pharmacokinetics (PK) of moxetumomab pasudotox was studied in 68 patients with HCL at a dose of 0.04 mg/kg administered intravenously over 30 minutes on Days 1, 3, and 5 of a 28-day cycle. PK exposure increased after subsequent infusions compared with the first infusion, which is likely related to the depletion of malignant B cells after treatment with moxetumomab pasudotox and subsequent reduction of the CD22 sink      ough concentration levels were negligible, indicating

there was no systemic accumulation        tumomab pasudotox.

Distribution

Based on noncompartmental PK analysis and consistent with restriction to extracellular fluid, the mean Cycle 1 Day 5 volume of distribution was 6.06 L, with an inter individual variability (CV) of

rough which moxetumomab pasudotox is metabolised has not been other protein therapeutics, moxetumomab pasudotox is expected to undergo adation into small peptides and amino acids via catabolic pathways.

El:

Based on noncompartmental PK analysis, moxetumomab pasudotox Cycle 1 Day 5 estimated mean (CV%) systemic clearance was 4.8 L/hr (82.3%) and the mean elimination half-life (t1/2) was 2.32 hours (range: 0.17 to 57.4). The elimination half-life following the first dose (Cycle 1 Day 1) could only be estimated in 6 out of 68 patients (mean t1/2=0.98 hours).

The primary elimination pathways of moxetumomab pasudotox are assumed to include CD22-mediated internalisation and proteolysis or catabolism. Renal excretion has not been studied for moxetumomab pasudotox. Data from a similar precursor compound indicate that intact protein is excreted into urine. However, renal excretion is not expected to be a major elimination pathway due to the molecular size.

Special populations

Age (34 to 84 years), sex, race, mild hepatic impairment (total bilirubin > ULN to 1.5 x ULN or AST > ULN; n=7), or mild renal impairment (creatinine clearance 60–89 mL/min; n=19), had no clinically meaningful effect on the PK of moxetumomab pasudotox, based on an analysis of noncompartmental PK data by covariates. With body weight dosing, a trend of increased exposure was observed with increasing weight. No dose adjustments are recommended for these demographics.

Moxetumomab pasudotox has not been studied in patients with moderate or severe hepatic impairment (total bilirubin >1.5 ULN or AST = Any) and moderate or severe renal impairment (creatinine clearance <60 mL/min).

Immunogenicity

There is a trend of reduced Cmax with increased ADA titre at later treatment cycles (Cycle 3 and beyond); however, these results are not conclusive due to the limitation of the bioanalytical met moxetumomab pasudotox at high ADA titres.

5.3 Preclinical safety data

Carcinogenicity and mutagenicity

No studies have been conducted to assess the carcinogenic or pasudotox.

Repeat-dose toxicity

Moxetumomab pasudotox was studied in cynomolgus monkeys for 13 weeks. At doses >10-times the human recommended dose, minimal to moderate d microscopically without corresponding changes in human recommended dose, microscopic evidence the brain and spinal cord, respectively, along with

Reproductive toxicology

Animal fertility studies have not been conducted with moxetumomab pasudotox. In a 3-month repeat-dose toxicity study using sexually mature cynomolgus monkeys, no adverse findings on male or female reproductive organs were observed at doses approximately 34-times the human recommended dose.

Powder for con

Sodium dihydrogen phosphate monohydrate

Sucrose

Glycine

Polysorbate 80

Sodium hydroxide

Solution (stabiliser)

Citric acid monohydrate

Sodium citrate

Polysorbate 80

Water for injections

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

No incompatibilities between Lumoxiti and 9 mg/mL (0.9%) sodium chloride in polyvinylchloride or polyolefin intravenous bags have been observed.

Do not co-administer other medicinal products through the same intravenous line.

6.3 Shelf life

Unopened vial

• 4 years.

Lumoxiti concentrate (i.e. reconstituted Lumoxiti powder for concentrate)

The Lumoxiti concentrate should be immediately further diluted.

From a microbiological point of view, unless the method of reconstitution 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.

Lumoxiti solution (i.e. diluted Lumoxiti concentrate in the prepared infusion b Chemical and physical in-use stability has been demonstrated for 24 hours at 2 room temperature up to 25°C.

From a microbiological point of view, the product should be use immediately, in-use storage times and conditions prior to use are would normally not be longer than 24 hours at 2°C – 8°C, unless and validated aseptic conditions.

6.4 Special precautions for storage

Store and transport refrigerated (2°C – 8°C). Do not freeze.

Store in the original carton in order to prot

d dilution of the medicinal product, see section 6.3.

6.5 Nature and contents of

Lumoxiti 1 mg powder for cntrate is provided in a Type 1 glass vial with an elastomeric stopper and a dark blue flip-off aluminium seal.

The 1 mL solution (stabiliser) is provided in a Type 1 glass vial with an elastomeric stopper and a dark grey flip-off aluminium seal.

ntains:

of powder for concentrate and 1 vial of solution (stabiliser) or

of powder for concentrate and 1 vial of solution (stabiliser)

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

For single use only. Lumoxiti powder for concentrate must be reconstituted and diluted by a healthcare professional using aseptic technique.

Step 1: Calculate dose

• •   Calculate the dose (mg) and the number of Lumoxiti powder for concentrate vials (1 mg/vial) to

be reconstituted.

Number of vials of Lumoxiti powder for concentrate = 0.04mg/kg x patient weight (kg)

1 mg/vial

o Do not round down for partial vials. For example, a person whose body weight is 55 kg would need 3 vials of Lumoxiti powder for concentrate.

• • Individualise dosing based on the patient's actual body weight prior to the first dose of the first

treatment cycle.

o A change in dose should only be made between cycles when a change in weight of greater than 10% is observed from the weight used to calculate the first dose of the first treatment cycle. No change in dose should be made during a particular cycle.

Step 2: Reconstitute Lumoxiti vials

Lumoxiti powder for concentrate must be reconstituted with water for injections. Water for is not provided in the pack.

A solution (stabiliser) is provided inside the Lumoxiti carton and is added to the infusion ba addition of reconstituted powder for concentrate. Do not use this solution (stabiliser) for reconstitution of the powder for concentrate.

Reconstitute each Lumoxiti powder for concentrate vial with 1.1 mL water for injections.

o Direct the water for injection along the walls of the vial and not directly at the lyophilised

Obtain a 50 mL sodium chloride 9 mg/mL (0.9%) solution for injection infusion bag.

Add 1 mL solution (stabiliser) to the infusion bag.

o Gently invert the bag to mix the solution. Do not shake.

d Lumoxiti concentrate to infusion bag

Withdraw the required volume (calculated from Step 1) of Lumoxiti concentrate from the reconstituted vial(s).

• • Inject Lumoxiti concentrate from the reconstituted vial(s) into the infusion bag containing 50 mL

sodium chloride 9 mg/mL (0.9%) solution for injection and 1 mL solution (stabiliser).

• • Gently invert the bag to mix the solution. Do not shake.
• • Visually inspect the diluted Lumoxiti concentrate (i.e. Lumoxiti solution). Do not use if this solution is cloudy or contains any particles.

Following this dilution step, infuse the Lumoxiti solution (from the final infusion bag) immediately (step 5).

Step 5 : Administer Lumoxiti

• • Immediately administer the Lumoxiti solution intravenously over 30 minutes. Use an infusion set

fitted with a sterile, low-protein binding 0.22 micron in-line filter.

• • Do not mix Lumoxiti, or administer as an infusion with other medicinal products.
• • After the infusion, flush the intravenous administration line with sodium chloride 9 mg/mL (0.9%) solution for injection at the same rate as the infusion. This ensures the full Lumoxiti dose is delivered.

7. MARKETING AUTHORISATION HOLDER

AstraZeneca AB

SE-151 85 Södertälje

Sweden

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/20/1522/001

EU/1/20/1522/002

9. DATE OF FIRST AUTHORISATION/RE