Special Warning : אזהרת שימוש

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

Sacituzumab govitecan can cause severe or life-threatening neutropenia (see section 4.8). Fatal infections in the setting of neutropenia have been observed in clinical studies with sacituzumab govitecan. 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 (see sections 4.2 and 4.8).


Diarrhoea

Sacituzumab govitecan can cause severe diarrhoea (see section 4.8). Diarrhoea in some cases was observed to have led to dehydration and subsequent acute kidney injury. 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 (see section 4.2 and 4.8). 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 (see section 4.8).
Anaphylactic reactions have been observed in clinical studies with sacituzumab govitecan and the use of sacituzumab govitecan is contraindicated in patients with a known hypersensitivity to sacituzumab govitecan (see section 4.3).

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 (see section 4.2).

Nausea and vomiting

Sacituzumab govitecan is emetogenic (see section 4.8). 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 (see section 4.2). 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 at increased risk for neutropenia, febrile neutropenia, and anaemia and are at increased risk for other adverse reactions following initiation of sacituzumab govitecan treatment (see section 4.8). 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 (see section 4.6).

Sodium

This medicinal product will be further prepared for administration with sodium-containing solution (see section 6.6) and this should be considered in relation to the total sodium intake to the patient from all sources per day.

Effects on Driving

4.7    Effects on ability to drive and use machines

Sacituzumab govitecan has minor influence on the ability to drive and use machines, e.g. dizziness, fatigue (see section 4.8).