Sacituzumab govitecan parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of sacituzumab govitecan.
Drugs List
Therapeutic Indications
Uses
Breast cancer
Treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received at least two prior lines of systemic therapy, with at least one of them given for unresectable locally advanced metastatic disease.
Dosage
Adults
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
10mg/kg once weekly on days 1 and 8 of 21-day treatment cycles.
Additional Dosage Information
Premedication
Prior to each dose of sacituzumab govitecan, premedication for infusion reactions and prevention of chemotherapy induced nausea and vomiting is recommended:
Premedicate with antipyretics, and H1 and H2 blockers prior to the sacituzumab govitecan infusion. Corticosteroids may be used for patients who have 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).
Dose modification
Infusion related reactions
If infusion related reaction occurs, reduce infusion rate or interrupt infusion. If life-threatening infusion related reaction occurs, permanently discontinue the infusion.
Severe neutropenia
Grade 4 neutropenia for greater than or equal to 7 days, or Grade 3 febrile neutropenia, or Grade 3/4 neutropenia which delays dosing by 2 or 3 weeks for recovery to less than or equal to Grade 1: Upon first occurrence, reduce dose by 25% and administer granulocyte-colony stimulating factor (G-CSF). Upon second occurrence, reduce dose by 50%. Upon third occurrence, discontinue treatment.
Grade 3/4 neutropenia which delays dosing by more than 3 weeks for recovery to less than or equal to Grade 1: Upon first occurrence, discontinue treatment.
Severe non-neutropenic toxicity
Grade 4 non-haematologic toxicity which recovers to less than or equal to Grade 1 within 3 weeks, or any Grade 3/4 nausea, vomiting or diarrhoea due to treatment that is not controlled with antiemetics and anti-diarrhoeal agents, or any Grade 3/4 non-haematologic toxicity persisting for greater than 48 hours despite optical medical management, or Grade 3/4 non-neutropenic haematologic or non-haematologic toxicity, which delays dosing by 2 or 3 weeks for recovery to less than or equal to Grade 1: Upon first occurrence, reduce dose by 25%. Upon second occurrence, reduce dose by 50%. Upon third occurrence, discontinue treatment.
Grade 3/4 non-neutropenic haematologic or non-haematologic toxicity, Grade 3 nausea or Grade 3/4 vomiting, which does not recover to less than or equal to Grade 1 within 3 weeks: Upon first occurrence, discontinue treatment.
Administration
For intravenous infusion only. First infusion should be administered over 3 hours, if this infusion is tolerated then the subsequent infusion should be administered over 1 to 2 hours.
Contraindications
Children under 18 years
Grade 3 nausea
Grade 3 vomiting
Neutrophil count below 1.5 x 10 to the power of 9 / L at baseline
Breastfeeding
Moderate hepatic impairment
Moderate renal impairment
Neutropenic fever
Pregnancy
Serum bilirubin above 1.5 times upper limit of normal
Serum transaminases above 3 times upper limit of normal
Serum transaminases above 5x ULN with concurrent liver metastasis
Severe diarrhoea
Precautions and Warnings
UGT1A1*28 homozygous genotype
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Consider pre-medication with antihistamines and/or antipyretics
Consider premedication with a corticosteroid
Prophylactic G-CSF should be considered
Treatment to be initiated and supervised by a specialist
Contains polysorbate
Consult local policy on the safe use of anti-cancer drugs
Must be diluted before use
Record name and batch number of administered product
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Consider the use of fluid and electrolyte replacement
Monitor complete blood counts before each dose
Monitor patient for 30 minutes after administration
Advise patient to report diarrhoea
Consider G-CSF in severe neutropenia / agranulocytosis
Consider prophylactic atropine to prevent acute severe cholinergic syndrome
Interrupt therapy/reduce infusion rate if infusion-related reactions occur
Suspend/reduce dose if grade 3 diarrhoea despite anti-diahorreal treatment
Suspend/reduce dose if grade 3 nausea despite anti-emetic treatment
Advise patient to seek advice at first indications of pregnancy
Consider dose interruption & reduction in non-haematological toxicity
Discontinue permanently if life threatening infusion reactions occur
Suspend treatment if grade 3 vomiting unresponsive to antiemetic occurs
Female: May cause infertility
Female: Contraception required during and for 6 months after treatment
Male: Contraception required during and for 3 months after treatment
Breastfeeding: Do not breastfeed during & for 1 month after treatment
Advise patient to report signs / symptoms of infusion related reactions
Patients should be observed during the infusion and for 30 minutes following the infusion for any signs or symptoms of infusion-related reactions.
Neutropenia
Sacituzumab govitecan can cause severe or life-threatening. Sacituzumab govitecan should not be administered if the absolute neutrophil count (ANC) is below 1500/mm cubed on Day 1 of any cycle, or if the ANC is below 1000/mm cubed on Day 8 of any cycle. Administration of granulocyte-colony stimulating factor (G-CSF) and dose reduction are required due to severe neutropenia or febrile neutropenia.
Diarrhoea
Sacituzumab govitecan can cause severe diarrhoea and should not be administered in cases of Grade 3/4 diarrhoea at the time of scheduled treatment. Patients should contact their healthcare provider immediately if they experience diarrhoea for the first time during treatment. If no infectious cause can be identified as the cause for the onset of diarrhoea, then loperamide 4mg initially, followed by 2mg with every episode of diarrhoea for a maximum of 16mg daily should be promptly initiated. Fluid and electrolyte substitution may also be required as additional supportive measures. Patients should contact their healthcare provider immediately if they experience melena, haematochezia, dehydration, an inability to tolerate oral fluids or manage diarrhoea within 24 hours. Patients who exhibit an excessive cholinergic response to treatment with sacituzumab govitecan can receive appropriate premedication (e.g. atropine) for subsequent treatments.
Nausea and vomiting
Sacituzumab govitecan is emetogenic should not be administered in cases of Grade 3 nausea or Grade 3/4 vomiting at the time of scheduled treatment, and should only be continued with additional supportive measures when resolved to less than or equal to Grade 1. Premedication with a two or three drug combination regimen (e.g. dexamethasone with either a 5-HT3 receptor antagonist or an NK-1 receptor) is recommended for prevention of chemotherapy induced nausea and vomiting.
Reduced UGT1A1 activity
Patients 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 sacituzumab govitecan treatment. Patients with known reduced UGT1A1 should be closely monitored for adverse reactions. Withhold or permanently discontinue sacituzumab govitecan based on clinical assessment of the observed adverse reactions in patients with evidence of acute early onset or unusually severe adverse reactions which may indicate reduced UGT1A1 activity.
Pregnancy and Lactation
Pregnancy
Sacituzumab govitecan is contraindicated during pregnancy.
The manufacturer recommends that sacituzumab is not recommended during pregnancy. Based on the mechanism of action, sacituzumab govitecan can cause teratogenicity and/or embryo-foetal lethality when administered during pregnancy.
Lactation
Sacituzumab govitecan is contraindicated during breastfeeding.
The manufacturer recommends that sacituzumab is not recommended during breastfeeding and for 1 month after the last dose. It is not known whether sacituzumab govitecan or its metabolites are excreted in human milk.
Side Effects
Abdominal distension
Abdominal pain
Allergic conjunctivitis
Alopecia
Anaemia
Anaphylactic reaction
Arthralgia
Aspartate aminotransferase increased
Asthma
Back pain
Bronchitis
Bronchospasm
Chest discomfort
Choking
Conjunctivitis
Constipation
Contact dermatitis
Cough
Decrease in haemoglobin
Decreased appetite
Dehydration
Dermatitis
Dermatitis acneiform
Diarrhoea
Dizziness
Dry skin
Dysgeusia
Dyspnoea
Epistaxis
Erythema
Erythematous rash
Eye pruritus
Fatigue
Febrile neutropenia
Flushing
Headache
Hyperglycaemia
Hypersensitivity reactions
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Hypophosphataemia
Hypotension
Insomnia
Leukopenia
Localised oedema
Lymphopenia
Macular rash
Maculopapular rash
Mouth ulcers
Nausea
Neutropenia
Oedema
Periorbital oedema
Pneumonia
Pruritic rash
Pruritus
Pustular rash
Pyrexia
Rash
Reduced lymphocyte count
Reduced neutrophil count
Respiratory failure
Rhinitis
Scrotal oedema
Seasonal allergy
Skin exfoliation
Stomatitis
Swelling
Tachypnoea
Throat tightness
Tongue swelling
Upper respiratory tract infection
Urinary tract infections
Urticaria
Vomiting
Weight loss
Wheezing
White blood cell count decreased
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: November 2021
Reference Sources
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 19 November 2021
Summary of Product Characteristics: Trodelvy 180 mg powder for concentrate for solution for infusion. Gilead Sciences Ltd. Revised September 2021.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.