TRODELVY 180 MG POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION - summary of medicine characteristics

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

1 NAME OF THE MEDICINAL PRODUCT

Trodelvy 180mg Powder for concentrate for solution for infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Sacituzumab govitecan

Each vial contains 180 mg sacituzumab govitecan. After reconstitution, one mL of solution contains 10 mg sacituzumab govitecan.

Sacituzumab is produced in Sp2/0-Ag14 cells by recombinant DNA technology.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder for concentrate for solution for infusion (powder for concentrate).

Off-white to yellowish lyophilized powder in a single-dose vial.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

TRODELVY is indicated for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior lines of systemic therapies, at least one of them given for unresectable locally advanced or metastatic disease (see section 5.1).

4.2 Posology and method of administration

TRODELVY must only be prescribed and administered to patients by healthcare professionals experienced in the use of anti-cancer therapies and should be administered in an environment where resuscitation facilities are available (see section 4.3 and 4.4).

Posology

The recommended dose of TRODELVY is 10 mg/kg administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles. Continue treatment until disease progression or unacceptable toxicity.

Premedication

Prior to each dose of TRODELVY, premedication for prevention of infusion reactions and prevention of chemotherapy-induced nausea and vomiting (CINV) is recommended:

Premedicate with antipyretics, and H1 and H2 blockers prior to infusion, and corticosteroids may be used for patients who had prior infusion reactions.

Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist, as well as other drugs as indicated).

Dose modifications for infusion-related reactions

The infusion rate of TRODELVY should be slowed down or infusion interrupted if the patient develops an infusion-related reaction. TRODELVY should be permanently discontinued if life-threatening infusion-related reactions occur, see section 4.4 Special warnings and precautions for use.

Dose modifications for adverse reactions

Dose modifications to manage adverse reactions of TRODELVY are described in Table 1. The TRODELVY dose should not be re-escalated after a dose reduction for adverse reactions has been made.

Table 1: Recommended dose modifications for adverse reactions

Grading according to NCI-CTCAE v.4.03

NCI-CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events

Special populations

Elderly

No overall differences in safety and effectiveness were observed between patients > 65 years old and younger patients.

Hepatic impairment

No adjustment to the starting dose is required when administering TRODELVY to patients with mild hepatic impairment (see section 5.2)

The safety of TRODELVY in patients with moderate or severe hepatic impairment has not been established. TRODELVY has not been studied in patients with serum bilirubin > 1.5 ULN, or AST and ALT > 3 ULN in patients without liver metastases, or AST and ALT > 5 ULN in patients with liver metastases. The use of TRODELVY is not recommended in these patients.

Renal impairment

No adjustment to the starting dose is required when administering TRODELVY to patients with mild renal impairment. TRODELVY has not been studied in patients with moderate renal impairment, severe renal impairment, or end-stage renal disease.

Paediatric population

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

Method of administration

TRODELVY should only be administered as an intravenous infusion, not as an intravenous push or bolus.

First infusion: the infusion should be administered over a period of 3 hours. Patients have to be observed during the infusion and for at least 30 minutes following the initial dose, for signs or symptoms of infusion-related reactions.

Subsequent infusions: the infusion should be administered over a period of 1 to 2 hours if prior infusions were tolerated. Patients have to be observed during the infusion and for at least 30 minutes after the infusion.

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

4.3 Contraindications

Hypersensitivity to the active substance, to any of the excipients listed in section 6.1, or to previous irinotecan therapy

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 clearly recorded.

Neutropenia

TRODELVY can cause severe or life-threatening neutropenia. TRODELVY should not be administered if the absolute neutrophil count is below 1500/mm3 on Day 1 of any cycle or if the neutrophil count is below 1000/mm3 on Day 8 of any cycle.

Therefore, it is recommended that patients’ blood counts are routinely tested prior to each dose of TRODELVY and as clinically indicated. TRODELVY should not be administered in case of neutropenic fever. Administration of G-CSF and dose reduction are required due to severe neutropenia or febrile neutropenia (see section 4.2). Consider G-CSF for secondary prophylaxis.

Diarrhoea

TRODELVY can cause severe diarrhoea. TRODELVY should not be administered in case of Grade 3–4 diarrhoea at the time of scheduled treatment and treatment should only be continued when resolved to < Grade 1 (see section 4.2).

Patients should be advised of the risk of diarrhoea and be closely monitored. Instruct patients to immediately contact their healthcare provider if they experience diarrhoea for the first-time during treatment.

At the onset of diarrhoea, and if no infectious cause can be identified, promptly initiate loperamide 4 mg initially followed by 2 mg with every episode of diarrhoea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhoea resolves. In patients with infectious diarrhoea, initiate anti-infective treatment as clinically indicated. Additional supportive measures (e.g. fluid and electrolyte substitution) may also be employed as clinically indicated.

Instruct patients to immediately contact their healthcare provider if they experience melena, haematochezia, dehydration, an inability to tolerate oral fluids or an inability to manage diarrhoea within 24 hours.

Patients who exhibit an excessive cholinergic response to treatment with TRODELVY (e.g. abdominal cramping, diarrhoea, salivation, etc.) can receive appropriate premedication (e.g. atropine) for subsequent treatments.

Hypersensitivity

TRODELVY can cause severe and life-threatening hypersensitivity. Anaphylactic reactions have been observed in clinical trials with TRODELVY and the use of TRODELVY is contraindicated in patients with a known hypersensitivity to sacituzumab govitecan (see section 4.3). Other hypersensitivity events observed during and within 24 hours following the infusion included dyspnoea; rash; pruritus; hypotension; rash; wheezing; oedema including facial and tongue; urticaria; and bronchospasm. Inform patients of the risk of serious infusion reactions and anaphylaxis. Instruct patients to immediately contact their healthcare provider if they experience these signs and symptoms. Medication to treat life-threatening hypersensitivity, as well as emergency equipment, should be available for immediate use.

Infusion-related reactions

Pre-infusion medication for patients receiving TRODELVY is recommended (see section 4.2). Patients should be closely observed for infusion-related reactions during each TRODELVY infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use. The infusion rate of TRODELVY should be slowed down or infusion interrupted if the patient develops an infusion-related reaction. TRODELVY should be permanently discontinued if life-threatening infusion-related reactions occur (see section 4.2).

Nausea and vomiting

TRODELVY is emetogenic. Premedication with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) is recommended for prevention of chemotherapy-induced nausea and vomiting (CINV).

TRODELVY should not be administered in case of Grade 3 nausea or Grade 3–4 vomiting at the time of scheduled treatment administration and treatment should only be continued with additional supportive measures when resolved to < Grade 1 (see section 4.2).

Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased risk of adverse reactions in patients with reduced UGT1A1 activity

Individuals who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk of severe neutropenia, severe diarrhoea, febrile neutropenia, and anaemia and may be at increased risk for other adverse reactions following initiation of TRODELVY treatment (see section 4.8). Patients with known reduced UGT1A1 activity should be closely monitored for adverse reactions. Withhold or permanently discontinue TRODELVY based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 activity (see section 4.2).

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed. SN-38 (the small molecule moiety of sacituzumab govitecan) is primarily metabolised via UGT1A1. Inhibitors or inducers of UGT1A1 are expected to increase or decrease SN-38 exposure, respectively.

UGT1A1 inhibitors

Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. TRODELVY should be used with caution with UGT1A1 inhibitors (e.g. propofol, ketoconazole, EGFR tyrosine kinase inhibitors), and patients should be closely monitored.

UGT1A1 inducers

Exposure to SN-38 may be substantially reduced in patients concomitantly receiving UGT1A1 enzyme inducers. TRODELVY should be used with caution with UGT1A1 inducers (e.g. carbamazepine, phenytoin, rifampicin, protease inhibitors), and patients should be closely monitored.

CYP3A

SN-38 (the small molecule moiety of sacituzumab govitecan) is primarily metabolised via UGT1A1. Inhibitors or inducers of CYP3A are not anticipated to impact SN-38 exposure.

4.6 Fertility, pregnancy and lactation

Pregnancy

Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-foetal lethality when administered during pregnancy. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells. TRODELVY is not recommended during pregnancy. Advise female patients to contact their healthcare provider if they are pregnant or become pregnant. Inform female patients of the risk to the foetus and potential loss of the pregnancy.

Women of Childbearing Potential / Contraception in Males and Females

Women of childbearing potential have to use effective contraception during treatment and for 6 months after the last dose. Male patients with female partners of childbearing potential have to use effective contraception during treatment with TRODELVY and for 3 months after the last dose. The pregnancy status of women of childbearing potential should be verified prior to the initiation of TRODELVY.

Breast-feeding

It is unknown whether TRODELVY or metabolites are excreted in human milk. Breast-feeding should be discontinued during treatment with TRODELVY and for 1 month after the last dose.

Fertility

Based on findings in animals, TRODELVY may impair fertility in females of reproductive potential.

4.7 Effects on ability to drive and use machines

TRODELVY has minor influence on the ability to drive and use machines. Dizziness has been reported. Advise patients to use caution when driving or using machines.

4.8 Undesirable effects

Summary of the safety profile

The safety profile for TRODELVY is derived from pooled data from two clinical studies (IMMU-132–01 and IMMU-132–05 [N=258; ASCENT]) involving 366 patients who received TRODELVY 10 mg/kg for the treatment of TNBC (the Overall TNBC population). The median exposure to TRODELVY in this data set was 4.9 months.

The most common adverse drug reactions (ADRs) (reported at a frequency of >20%) in the overall TNBC population were diarrhoea (64.5%), nausea (64.2%), neutropenia (64.2%), fatigue (52.5%), alopecia (44.3%), anaemia (43.2%), vomiting (38.0%), constipation (36.3%), decreased appetite (28.1%), cough (22.7%), and abdominal pain (20.8%).

The most common serious adverse reactions (reported at a frequency of > 3%) were febrile neutropenia (4.5%), diarrhoea (3.8%), and pneumonia (3%). Fatal adverse reactions occurred in 0.5% of patients who received TRODELVY, including respiratory failure (0.3%).

The most common Grade 3 or higher ADRs (reported at a frequency of > 2%) were neutropenia (49.5%), leukopenia (12.0%), diarrhoea (10.7%), anaemia (10.1%), febrile neutropenia (6.6%), fatigue (5.2%), hypophosphataemia (5.2%), nausea (4.1%), dyspnoea (3.6%), pneumonia (3.3%), vomiting (3.0%), hypokalaemia (2.5%), lymphopenia (2.5%), abdominal pain (2.2%), and aspartate aminotransferase increased (2.2%). A higher proportion of patients with body weight > 95 kg experienced Grade 3 or higher ADRs on TRODELVY 10 mg/kg.

The most common ADRs leading to treatment interruption (reported at a frequency of > 2%) were neutropenia (41.8%), leukopenia (6.0%), diarrhoea (4.4%), anaemia (3.8%), pyrexia (2.5%), and febrile neutropenia (2.2%).

The most common ADRs leading to dose reduction reported (at a frequency of > 2%) were neutropenia (6.3%) and diarrhoea (3.3%).

The most common ADRs leading to treatment discontinuation (reported in >1 patient) were fatigue (0.8%) and pneumonia (0.5%).

Adverse reactions in patients with reduced UGT1A1 activity

In 91.0% (333/366) of patients the Overall TNBC population had retrospective UGT1A1 genotype results available, the incidence of Grade 3 or higher neutropenia in IMMU-132–05 and anaemia were 56.1% (23/41) and 19.5% (8/41), respectively, in patients homozygous for the UGT1A1*28 allele, 46.7% (63/135) and 6.7% (9/135), respectively, in patients heterozygous for the UGT1A1*28 allele, and 52.9% (83/157) and 8.3% (13/157), respectively, in patients homozygous for the wild-type allele. (See sections 4.2 and 4.4)

Tabulated list of adverse reactions

Table 2 lists adverse reactions from the Overall TNBC population. The adverse reactions are classified by System Organ Class and sorted by frequencies calculated from all reported events, using the following convention: very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1,000 to < 1/100); rare (> 1/10,000 to < 1/1,000); very rare (< 1/10,000) or not known (cannot be estimated from available data).

Table 2: Adverse reactions observed in the Overall TNBC Population, comprising of patients treated with TRODELVY in studies IMMU-132–01 and IMMU-132–05

1: No frequency is provided for those events for which a Grade >3 event was not observed among the pooled safety data.

2: Includes the following preferred terms: neutropenia; neutrophil count decreased.

3: Includes the following preferred terms: anaemia; haemoglobin decreased; red blood cell count decreased.

4: Includes the following preferred terms: leukopenia; white blood cell count decreased.

5: Includes the following preferred terms: lymphopenia; lymphocyte count decreased.

6: Hypersensitivity events reported up to the end of the day after treatment was administered. Includes events coded to the following preferred terms: Cough; dyspnoea; rash; pruritus; stomatitis; hypotension; rash maculopapular; flushing; erythema; chest discomfort; hypersensitivity; rhinitis allergic; wheezing; localized oedema; dermatitis acneiform; conjunctivitis; rash pruritic; oedema; rash macular; rash pustular; swelling; swelling face; urticaria; anaphylactic reaction; asthma; bronchospasm; conjunctivitis allergic; dermatitis; dermatitis contact; eye pruritus; mouth ulceration; periorbital oedema; rash erythematous; scrotal oedema; seasonal allergy; skin exfoliation; swollen tongue; tachypnoea; throat tightness; Type IV hypersensitivity reaction; choking.

Description of selected adverse reactions

Neutropenia

In IMMU-132–05, neutropenia occurred in 64.0% (165/258) of patients in the TRODELVY arm compared to 43.8% (98/224) of patients in the Treatment of Physician’s Choice (TPC; chosen from one of the following single-agent chemotherapies: eribulin, vinorelbine, gemcitabine or capecitabine) arm. Grade 3–4 neutropenia occurred in 51.9% (134/258) of patients in the TRODELVY arm compared to 33.9% (76/224) of patients in the TPC arm. The incidence of neutropenia in the Overall TNBC population was similar (64.2%). In the Overall TNBC population, no patients in the TRODELVY arm had neutropenia leading to permanent discontinuation.

Granulocyte-colony stimulating factor (G-CSF) was used beyond treatment cycle 1 in 43.2% (158/366) of patients who received TRODELVY; for prophylaxis for neutropenia (23.5%; 86/366) and/or treatment of neutropenia (27.0%; 99/366).

The median time to onset of neutropenia following the start of the first treatment cycle was 15 days [1–302 days]. Neutropenia was reversible with a median duration of 8 days [1–200 days].

In IMMU-132–05, febrile neutropenia (all were Grade 3–4) occurred in 5.8% (15/258) of patients treated with TRODELVY compared to 2.7% (6/224) of patients in the TPC arm. Of the patients homozygous for the UGT1A1*28 allele, the incidence of febrile neutropenia was 17.6% (6/34). No patients had febrile neutropenia leading to permanent discontinuation.

Diarrhoea

In IMMU-132–05, diarrhoea occurred in 65.1% (168/258) of patients in the TRODELVY arm compared to 17.0% (38/224) of patients in the TPC arm. Grade 3 diarrhoea occurred in 11.2% (29/258) of patients in the TRODELVY arm compared to 0.9% (2/224) of patients in the TPC arm. No Grade 4 events were reported.

The incidence of diarrhoea in the Overall TNBC population was similar (64.5%). In the Overall TNBC population, 1 patient (< 1%) discontinued treatment because of diarrhoea, and neutropenic colitis was observed in 1 patient.

The median time to onset of diarrhoea following the start of the first treatment cycle was 13 days [1–364 days]. The median duration of diarrhoea was 8 days [1–183 days].

Hypersensitivity

In IMMU-132–05, hypersensitivity reactions within 24 hours of dosing occurred in 34.1% (88/258) of patients in the TRODELVY arm compared to 20.5% (46/224) of patients in the TPC arm. Grade 3–4 hypersensitivity occurred in 1.2% (3/258) of patients in the TRODELVY arm compared to 1.3% (3/224) of patients in the TPC arm. In the Overall TNBC population, the incidence of hypersensitivity was similar, and 1 patient discontinued treatment because of a hypersensitivity reaction.

Nausea and vomiting

In IMMU-132–05, nausea occurred in 62.4% (161/258) of patients in the TRODELVY arm compared to 30.4% (68/224) of patients in the TPC arm. Grade 3–4 nausea occurred in 3.1% (8/258) of patients compared to 0.4% (1/224) of patients in the TPC arm.

Vomiting occurred in 33.3% (86/258) of patients in the TRODELVY arm compared to 16.1% (36/224) of patients in the TPC arm. Grade 3–4 vomiting occurred in 1.6% (4/258) of patients in the TRODELVY arm compared to 1.3% (3/224) of patients in the TPC arm.

In the Overall TNBC population, the incidences of nausea and vomiting were similar.

Alopecia

In IMMU-132–05, alopecia occurred in 46.9% (121/258) of patients in the TRODELVY arm compared to 16.1% (36/224) of patients in the TPC arm.

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies may be misleading.

The immunogenicity of TRODELVY was evaluated in serum samples from 106 patients with mTNBC using an electrochemilu­minescence (ECL)-based immunoassay to test for anti-sacituzumab govitecan antibodies. Detection of the anti-sacituzumab govitecan antibodies was done using a 3-tier approach: screen, confirm, and titre. Anti-sacituzumab govitecan antibodies developed in 2% (2/106) of patients. The effect of immunogenicity on PK, safety, and efficacy is not yet known.

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

5   PHARMACOLOGICAL PROPERTIES

5.1   Pharmacodynamic properties

5.2 Pharmacokinetic properties

The serum pharmacokinetics of sacituzumab govitecan and SN-38 were evaluated in study IMMU-132–05 in a population of mTNBC patients who received sacituzumab govitecan as a single agent at a dose of 10 mg/kg. The pharmacokinetic parameters of sacituzumab govitecan and free SN-38 are presented in Table 6.

Table 5: Summary of Mean PK Parameters (CV%) of Sacituzumab Govitecan and Free SN-38

Cmax: maximum plasma concentration

AUC0–168: area under plasma concentration curve through 168 hours

Distribution

Based on population pharmacokinetic analyses, the central volume distribution of sacituzumab govitecan is 2.96 L.

Elimination

The mean half-life of sacituzumab govitecan and free SN-38 was 15.3 and 19.7 hours, respectively. Based on population pharmacokinetic analyses, the clearance of the sacituzumab govitecan is 0.14 L/h.

Metabolism

No metabolism studies with sacituzumab govitecan have been conducted. The glucuronide metabolite of SN-38 (SN-38G) was detectable in the serum of patients.

SN-38 (the small molecule moiety of sacituzumab govitecan) is metabolised via UGT1A1. Genetic variants of the UGT1A1 gene such as the UGT1A1*28 allele lead to reduced UGT1A1 enzyme activity. Individuals who are homozygous for the UGT1A1*28 allele are at increased risk for neutropenia, febrile neutropenia, and anaemia from TRODELVY (see sections 4.4 & 4.5). Approximately 20% of the Black or African American population, 10% of the White population, and 2% of the East Asian population are homozygous for the UGT1A1*28 allele. Decreased function alleles other than UGT1A1*28 may be present in certain populations.

Special Populations

Pharmacokinetic analyses in patients treated with TRODELVY (n = 527) did not identify an effect of age, race, or mild renal impairment on the pharmacokinetics of sacituzumab govitecan. Renal elimination is known to contribute minimally to the excretion of SN-38, the small molecule moiety of sacituzumab govitecan. There are no data on the pharmacokinetics of sacituzumab govitecan in patients with moderate or severe renal impairment or end-stage renal disease.

The exposure of sacituzumab govitecan is similar in patients with mild hepatic impairment (bilirubin < ULN and AST > ULN, or bilirubin > 1.0 to < 1.5 ULN and AST of any level; n = 59) to patients with normal hepatic function (bilirubin and AST < ULN; n = 191).

Sacituzumab govitecan exposure is unknown in patients with moderate or severe hepatic impairment. SN-38 exposure may be elevated in such patients due to decreased hepatic UGT1A1 activity.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional nonclinical safety studies. Effects in non-clinical studies were observed at levels considered sufficiently in excess of the maximum human exposure, those with possible relevance to clinical use were as follows.

SN-38 was clastogenic in an in vitro mammalian cell micronucleus test in Chinese hamster ovary cells and was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay.

In a repeat-dose toxicity study in cynomolgus monkeys, intravenous administration of sacituzumab govitecan resulted in endometrial atrophy, uterine haemorrhage, increased follicular atresia of the ovary, and atrophy of vaginal epithelial cells at doses > 60 mg/kg (1.9 times the human recommended dose of 10 mg/kg based on body weight allometric scaling).

No toxicity was attributed to the novel excipient, MES, upon evaluation in two in vitro cellular cytotoxicity assays either alone or in combination with sacituzumab govitecan at dose levels which exceed clinical exposure. In addition, the toxicity of MES was assessed in a mouse toxicity study and two repeat dose toxicity studies in monkeys. No adverse or toxicologically significant findings were observed for MES in repeat-dose toxicity studies at concentrations that exceeded clinical exposure.

6.1 List of excipients

2-(N-morpholino) ethane sulfonic acid (MES)

Polysorbate 80

Trehalose dihydrate

6.2 Incompatibilities

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

6.3

Unopened vial

24 months

After reconstitution

The infusion bag containing TRODELVY solution can be stored in a refrigerator (2°C-8°C) for up to 4 hours.

6.4 Special precautions for storage

Store in a refrigerator (2°C-8°C).

Do not freeze.

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

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

6.5 Nature and contents of container

Type 1 clear glass single-dose 50 mL vials, with a dark grey butyl rubber stopper and crimp-sealed with an aluminum flip-off cap.

Each pack contains one vial.

6.6 Special precautions for disposal

TRODELVY is a cytotoxic drug. Applicable special handling and disposal procedures have to be followed.

Reconstitution

Calculate the required dose (mg) of TRODELVY based on the patient’s body weight at the beginning of each treatment cycle (or more frequently if the patient’s body weight changed by more than 10% since the previous administration).

Allow the required number of vials to warm to room temperature.

Using a sterile syringe, slowly inject 20 mL of sodium chloride 0.9% solution for injection, into each 180 mg TRODELVY vial. The resulting concentration will be 10 mg/mL.

Gently swirl vials and allow to dissolve for up to 15 minutes. Do not shake. The product should be inspected visually for particulate matter and discoloration prior to administration. The solution should be free of visible particulates, clear and yellow. Do not use the reconstituted solution if it is cloudy or discoloured.

Use immediately to prepare a diluted TRODELVY solution for infusion.

Dilution

Calculate the required volume of the reconstituted TRODELVY solution needed to obtain the appropriate dose according to patient’s body weight. Withdraw this amount from the vial(s) using a syringe. Discard any unused portion remaining in the vial(s).

Adjust the volume in the infusion bag as needed with sodium chloride 0.9% solution for injection, to obtain a concentration of 1.1 mg/mL to 3.4 mg/mL (the total volume should not exceed 500 mL). For patients whose body weight exceeds 170 kg, divide the total dosage of TRODELVY equally between two 500 mL infusion bags and infuse sequentially via slow infusion.

Slowly inject the required volume of reconstituted TRODELVY solution into a polyvinyl chloride, polypropylene, or polypropylene copolymer infusion bag to minimise foaming. Do not shake the contents.

Only sodium chloride 0.9% solution for injection should be used since the stability of the reconstituted product has not been determined with other infusionbased solutions. Use the diluted solution in the infusion bag immediately. If not used immediately, the infusion bag containing TRODELVY solution can be stored refrigerated 2°C to 8°C for up to 4 hours. After refrigeration, administer diluted solution within 4 hours (including infusion time).

Do not freeze or shake. Protect from light.

Administration

Administer TRODELVY as an intravenous infusion. Protect infusion bag from light.

An infusion pump may be used.

Do not mix TRODELVY, or administer as an infusion, with other medicinal products.

Upon completion of the infusion, flush the intravenous line with 20 mL sodium chloride 0.9% solution for injection.

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