- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations of tucatinib.
Locally advanced or metastatic HER2-positive breast cancer in adults who have received at least 2 prior anti-HER2 treatment regimens, in combination with trastuzumab and capecitabine.
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
300mg twice daily.
Patients with Hepatic Impairment
Severe hepatic impairment (Child-Pugh C)
Recommended starting dose: 200mg twice daily.
Additional Dosage Information
Dose reductions for adverse reactions
Recommended starting dose: 300mg twice daily
First dose reduction: 250mg twice daily
Second dose reduction: 200mg twice daily
Third dose reduction: 150mg twice daily
Dose modifications for adverse reactions
Grade 1 or 2: No dose modification required.
Grade 3 diarrhoea without anti-diarrhoeal treatment: Initiate/intensify appropriate medical therapy. Withhold tucatinib treatment until recovery to less than or equal to Grade 1, then resume tucatinib treatment at the same dose level.
Grade 3 diarrhoea with anti-diarrhoeal treatment: Initiate/intensify appropriate medical therapy. Withhold tucatinib treatment until recovery to less than or equal to Grade 1, then resume tucatinib treatment at the next lower dose level.
Increased ALT, AST or bilirubin
Grade 1 bilirubin (greater than ULN up to 1.5 time ULN): No dose modification required.
Grade 2 bilirubin (greater than 1.5 times ULN up to 3 times ULN): Withhold tucatinib until recovery to less than or equal to Grade 1, then resume tucatinib treatment at the same dose level.
Grade 3 ALT or AST (greater than 5 times ULN up to 20 times ULN) OR Grade 3 bilirubin (greater than 3 times ULN up to 10 times ULN): Withhold tucatinib until recovery to less than or equal to Grade 1, then resume tucatinib treatment at the next lower dose level.
Grade 4 ALT or AST (greater than 20 times ULN) OR Grade 4 bilirubin (greater than 10 times ULN): Permanently discontinue tucatinib treatment.
ALT or AST greater than 3 times ULN AND bilirubin greater than 2 times ULN: Permanently discontinue tucatinib treatment.
Other adverse reactions
Grade 1 or 2: No dose modification required.
Grade 3: Withhold tucatinib treatment until recovery to less than or equal to Grade 1, then resume tucatinib treatment at the next lower dose level.
Grade 4: Permanently discontinue tucatinib treatment.
Children under 18 years
Precautions and Warnings
Patients over 80 years
Restricted potassium intake
Restricted sodium intake
Severe hepatic impairment
Contains more than 1 mmol (23 mg) sodium per dose
Anti-diarrhoeals may be required during treatment
Treatment to be initiated and supervised by a specialist
Contains potassium; caution in low potassium diets
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Monitor hepatic enzymes and bilirubin levels every 3 weeks
Monitor levels of hepatic enzymes and bilirubin
Suspend/reduce dose if grade 3 diarrhoea despite anti-diahorreal treatment
Consider other markers of renal function if creatinine is constantly raised
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue permanently if AST or ALT level exceeds 20 x ULN
Discontinue permanently if grade 4 diarrhoea occurs
Discontinue treatment if total bilirubin > 10 x ULN
Interrupt treatment if ALT or AST > 5 x ULN
Suspend treatment and/or reduce dose if total bilirubin > 3 x ULN
Suspend treatment if grade 3 or greater diarrhoea occurs
Suspend treatment if total bilirubin between 1.5 and 3 times ULN
Permanently discontinue treatment if grade 4 adverse reactions occur
Suspend treatment/reduce dose if grade 3 adverse reactions occur
Advise patient not to take St John's wort concurrently
Female: May cause infertility
Female: Contraception required during and for 1 week after treatment
Male: Contraception required during and for 1 week after treatment
Breastfeeding: Do not breastfeed during & for 1 week after treatment
Increase in serum creatinine has been observed due to inhibition of renal tubular transport of creatinine without affecting glomerular filtration function. Alternative markers such as BUN, cystatin C or calculated GFR, which are not base on creatinine should be used to determine whether renal function is impaired.
If diarrhoea occurs, antidiarrhoeals should be administered as clinically relevant. If grade 3 or 4 diarrhoea or diarrhoea of any grade with complicating features such as dehydration, fever or neutropenia occurs, then diagnostic tests should be performed to exclude infectious causes.
Sensitive CYP3A substrates
Tucatinib is a strong CYP3A inhibitor and should not be administered concomitantly with CYP3A substrates. If concomitant use is unavoidable, then CYP3A substrate dosage should be reduced.
Concomitant use of tucatinib with a p-gp substrate increased the plasma concentrations of p-gp substrate. Dose reduction of p-gp substrate should be considered and p-gp substrates should be administered with caution.
Strong CYP3A/moderate CYP2C8 inducers
Concomitant use of tucatinib and strong CYP3A or moderate CYP2C8 inducers decreased tucatinib concentrations, which may reduce tucatinib activity. Concomitant use of tucatinib and strong CYP3A or moderate CYP2C8 inducers should therefore be avoided.
Strong/moderate CYP2C8 inhibitors
Concomitant use of tucatinib and strong CYP2C8 inhibitors increased tucatinib concentrations, which may increase risk of tucatinib toxicity. Concomitant use of tucatinib and strong CYP2C8 inhibitors should therefore be avoided.
No clinical data is available on the effect of moderate CYP2C8 inhibitors on the concentration of tucatinib. Monitoring for tucatinib toxicity should be increased with concomitant use of moderate CYP2C8 inhibitors.
Pregnancy and Lactation
Tucatinib is contraindicated during pregnancy.
The manufacturer recommends that tucatinib should not be used during pregnancy unless the clinical condition of the woman requires treatment. Animal studies of tucatinib have shown reproductive toxicity.
Tucatinib is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding should be discontinued during tucatinib treatment and for 1 week after treatment. It is unknown whether tucatinib or its metabolites are excreted in human milk, therefore a risk to the infant cannot be excluded.
Alanine aminotransferase increased
Aspartate aminotransferase increased
Serum bilirubin increased
Toxic skin reaction
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 ).
Last Full Review Date: December 2021
Summary of Product Characteristics: Tukysa 50mg film-coated tablets. Seagen U.K. Ltd. Revised July 2021.
Summary of Product Characteristics: Tukysa 150mg film-coated tablets. Seagen U.K. Ltd. Revised July 2021.
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