Posology : מינונים

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 administered in an environment where full resuscitation facilities are available.


Posology

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 (see section 4.4).

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 (see section 4.4).

Dose modifications for adverse reactions

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


Table 1: Recommended dose modifications for adverse reactions

Adverse reaction                                                Occurrence   Dose modification Severe neutropenia
Grade 4 neutropenia ≥ 7 days or less if clinically indicated,   First        Administer granulocyte- OR                                                                           colony stimulating factor Grade 3-4 febrile neutropenia                                                (GCSF), as soon as OR                                                                           clinically indicated At time of scheduled treatment, Grade 3-4 neutropenia which     Second       25% dose reduction: delays dosing by 2 or 3 weeks for recovery to ≤ Grade 1                      administer G-CSF as soon as clinically indicated
Third        50% dose reduction: administer G-CSF as soon as clinically indicated
Fourth       Discontinue treatment: administer G-CSF as soon as clinically indicated
At time of scheduled treatment, Grade 3-4 neutropenia which     First        Discontinue treatment: delays dosing beyond 3 weeks for recovery to ≤ Grade 1                       administer G-CSF as soon as clinically indicated
Severe non-neutropenic toxicity
Grade 4 non-hematologic toxicity of any duration,               First        25% dose reduction OR                                                              Second       50% dose reduction Any Grade 3-4 nausea, vomiting or diarrhoea due to treatment    Third        Discontinue treatment that is not controlled with antiemetics and anti-diarrhoeal agents,
OR
Other Grade 3-4 non-hematologic toxicity persisting > 48 hours despite optimal medical management,
OR
At time of scheduled treatment, Grade 3-4 non-neutropenic hematologic or non-hematologic toxicity, which delays dose by
2 or 3 weeks for recovery to ≤ Grade 1
In the event of Grade 3-4 non-neutropenic hematologic or non-   First        Discontinue treatment hematologic toxicity, Grade 3 nausea or Grade 3-4 vomiting,
which does not recover to ≤ Grade 1 within 3 weeks

Special populations

Elderly
No overall differences in efficacy of sacituzumab govitecan were observed in patients ≥ 65 and < 65 years old. 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 any of the following: 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 or moderate renal impairment.

Sacituzumab govitecan has not been studied in patients with 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.

Method of administration

Sacituzumab govitecan is for intravenous use only. It must 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.

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 each infusion and for at least 30 minutes after each infusion for signs or symptoms of infusion-related reactions (see section 4.4).

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