Trodelvy

/ Gilead Sciences Israel Ltd.

This medicinal product must only be prescribed and administered to patients by healthcare professionals experienced in the use of anti-cancer therapies and administered in an environment where full resuscitation facilities are available.
The recommended dose of sacituzumab govitecan is 10 mg/kg body weight administered as an intravenous infusion once weekly on Day 1 and Day 8 of 21-day treatment cycles. Treatment should be continued until disease progression or unacceptable toxicity.
Prevention treatment:
Prior to each dose of sacituzumab govitecan, treatment for prevention of infusion-related reactions and prevention of chemotherapy-induced nausea and vomiting (CINV) is recommended.
Dose modifications for infusion-related reactions:
The infusion rate of sacituzumab govitecan should be slowed down or infusion interrupted if the patient develops an infusion-related reaction. Sacituzumab govitecan should be permanently discontinued if life-threatening infusion-related reactions occur.
Dose modifications for adverse reactions:
See prescribing information for dose modifications to manage adverse reactions of sacituzumab govitecan. The sacituzumab govitecan dose should not be re-escalated after a dose reduction for adverse reactions has been made.
Elderly:
No dose adjustment is required in patients ≥ 65 years old. Data from sacituzumab govitecan in patients ≥ 75 years are limited.
Hepatic impairment:
No adjustment to the starting dose is required when administering sacituzumab govitecan to patients with mild hepatic impairment (bilirubin ≤ 1.5 upper limit of normal [ULN] and aspartate aminotransferase [AST]/alanine aminotransferase [ALT] < 3 ULN). The safety of sacituzumab govitecan in patients with moderate or severe hepatic impairment has not been established. Sacituzumab govitecan has not been studied in patients with serum bilirubin > 1.5 ULN, or AST or ALT > 3 ULN in patients without liver metastases, or AST or ALT > 5 ULN, in patients with liver metastases. The use of sacituzumab govitecan should be avoided in these patients.
Renal impairment:
No adjustment to the starting dose is required when administering sacituzumab govitecan to patients with mild renal impairment.
Sacituzumab govitecan has not been studied in patients with moderate renal impairment, severe renal impairment or end-stage renal disease (Creatinine Clearance [CrCl] ≤ 15 mL/min).
Paediatric population:
The safety and efficacy of sacituzumab govitecan in children aged 0 to 18 years have not been established. No data are available.

Treatment of adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, including at least one of them for advanced disease.

Hypersensitivity to the active substance or to any of the excipients.

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:
Sacituzumab govitecan can cause severe or life-threatening neutropenia. Sacituzumab govitecan 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 monitored as clinically indicated during treatment. Sacituzumab govitecan should not be administered in case of neutropenic fever. Treatment with granulocyte-colony stimulating factor and dose modifications may be required due to severe neutropenia.
Diarrhoea:
Sacituzumab govitecan can cause severe diarrhoea. Sacituzumab govitecan 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. At the onset of diarrhoea, and if no infectious cause can be identified, treatment with loperamide should be initiated. Additional supportive measures (e.g. fluid and electrolyte substitution) may also be employed as clinically indicated.
Patients who exhibit an excessive cholinergic response to treatment with sacituzumab govitecan (e.g. abdominal cramping, diarrhoea, salivation, etc.) can receive appropriate treatment (e.g. atropine) for subsequent treatments with sacituzumab govitecan.
Hypersensitivity:
Sacituzumab govitecan can cause severe and life-threatening hypersensitivity. Anaphylactic reactions have been observed in clinical trials with sacituzumab govitecan and the use of sacituzumab govitecan is contraindicated in patients with a known hypersensitivity to sacituzumab govitecan.
Pre-infusion treatment, including antipyretics, H1 and H2 blockers, or corticosteroids (e.g. 50 mg hydrocortisone or equivalent, orally or intravenously), for patients receiving sacituzumab govitecan is recommended. Patients should be closely observed for infusion-related reactions during each sacituzumab govitecan infusion and for at least 30 minutes after completion of each infusion. The infusion rate of sacituzumab govitecan should be slowed down or infusion interrupted if the patient develops an infusion-related reaction. Sacituzumab govitecan should be permanently discontinued if life-threatening infusion-related reactions occur.
Nausea and vomiting:
Sacituzumab govitecan is emetogenic. Antiemetic preventive treatment with two or three medicinal products (e.g. dexamethasone with either a 5-hydroxytryptamine 3 [5-HT3] receptor antagonist or a Neurokinin-1 [NK-1] receptor antagonist as well as other medicinal products as indicated) is recommended for prevention of chemotherapy-induced nausea and vomiting (CINV).
Sacituzumab govitecan 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. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medicinal products with clear instructions for prevention and treatment of nausea and vomiting.
Use in patients with reduced UGT1A1 activity:
SN-38 (the small molecule moiety of sacituzumab govitecan) is metabolised via uridine diphosphate-glucuronosyl transferase (UGT1A1). Genetic variants of the UGT1A1 gene such as the UGT1A1*28 allele lead to reduced UGT1A1 enzyme activity. Individuals who are homozygous for UGT1A1*28 allele are potentially at increased risk for neutropenia, febrile neutropenia, and anaemia and may be at increased risk for other adverse reactions following initiation of sacituzumab govitecan treatment. Approximately 20% of the Black 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. Patients with known reduced UGT1A1 activity should be closely monitored for adverse reactions. When unknown, no testing of UGT1A1 status is required as the management of adverse reactions including the recommended dose modifications will be the same for all patients.
Embryo-foetal toxicity:
Based on its mechanism of action, sacituzumab govitecan can cause teratogenicity and/or embryo-foetal lethality when administered to a pregnant woman. Sacituzumab govitecan contains a genotoxic component, SN-38, and targets rapidly dividing cells. Pregnant women and women of childbearing potential should be informed of the potential risk to the foetus. The pregnancy status of females of reproductive potential should be verified prior to the initiation of sacituzumab govitecan.
Sodium:
This medicinal product will be further prepared for administration with sodium-containing solution and this should be considered in relation to the total sodium intake to the patient from all sources per day.

Very common: Urinary tract infection, upper respiratory tract infection, neutropenia, anaemia, leukopenia, lymphopenia, hypersensitivity, decreased appetite, hypokalaemia, hypomagnesaemia, hyperglycaemia, insomnia, headache, dizziness, cough, diarrhoea, nausea, vomiting, constipation, abdominal pain, alopecia , rash, pruritus, back pain, arthralgia, fatigue, weight decreased.
Common: Nasopharyngitis, sinusitis, bronchitis, influenza, oral herpes, febrile neutropenia, hypophosphataemia, hypocalcaemia, anxiety, dysgeusia, rhinorrhoea, nasal congestion, epistaxis, dyspnoea exertional, productive cough, upper airway cough syndrome, stomatitis, abdominal pain upper, gastrooesophageal reflux disease, abdominal distension, dry skin, rash maculopapular, musculoskeletal chest pain, muscle spasms, dysuria, haematuria, pain, chills, blood alkaline phosphatase increased, blood alkaline phosphatase increased.
See prescribing information for full details.

No interaction studies have been performed. Inhibitors or inducers of UGT1A1 are expected to increase or decrease SN-38 exposure, respectively.
UGT1A1 inhibitors:
Concomitant administration of sacituzumab govitecan with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inhibitors (e.g. propofol, ketoconazole, EGFR tyrosine kinase inhibitors).
UGT1A1 inducers:
Exposure to SN-38 may be substantially reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inducers (e.g. carbamazepine, phenytoin, rifampicin, ritonavir, tipranavir).

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 sacituzumab govitecan and for 3 months after the last dose.
Pregnancy:
There are no available data on the use of sacituzumab govitecan in pregnant women. However, based on its mechanism of action, sacituzumab govitecan can cause teratogenicity and/or embryo-foetal lethality when administered during pregnancy. Sacituzumab govitecan contains a genotoxic component, SN-38, and targets rapidly dividing cells.
Sacituzumab govitecan should not be used during pregnancy unless the clinical condition of the woman requires treatment with sacituzumab govitecan.
The pregnancy status of women of childbearing potential should be verified prior to the initiation of sacituzumab govitecan.
Women who become pregnant must immediately contact their doctor.
Breast-feeding:
It is unknown whether sacituzumab govitecan or its metabolites are excreted in human milk. A risk to breastfed newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with sacituzumab govitecan and for 1 month after the last dose.
Fertility:
Based on findings in animals, sacituzumab govitecan may impair fertility in females of reproductive potential. No human data on the effect of sacituzumab govitecan on fertility are available.

In clinical studies, doses of up to 18 mg/kg (approximately 1.8 times the maximum recommended dose of 10 mg/kg body weight) led to a higher incidence of severe neutropenia.
In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, in particular severe neutropenia, and appropriate treatment instituted.

This is a cytotoxic medicinal product. Applicable special handling and disposal procedures have to be followed.
Store in a refrigerator (2°C – 8°C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
See prescribing information for storage conditions after reconstitution and dilution of the medicinal product.