Drugs List

Therapeutic Indications

Uses

Breast cancer

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.

Contraindications

Children under 18 years
Breastfeeding
Pregnancy

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

Laboratory tests
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.

Diarrhoea
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.

P-gp substrates
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

Pregnancy

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.

Lactation

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.

Side Effects

Alanine aminotransferase increased
Allergic dermatitis
Aphthous ulcers
Arthralgia
Aspartate aminotransferase increased
Dermatitis acneiform
Diarrhoea
Dysaesthesia
Epistaxis
Erythema
Erythematous rash
Glossodynia
Hyperbilirubinaemia
Lip blister
Lip ulceration
Macular rash
Maculopapular rash
Mouth ulcers
Nausea
Oral pain
Oropharyngeal pain
Papular eruption
Pruritic rash
Pustular rash
Rash
Serum bilirubin increased
Skin exfoliation
Stomatitis
Tongue blistering
Tongue ulceration
Toxic skin reaction
Urticaria
Vomiting
Weight loss

Presentation

Oral formulations of tucatinib.

Drugs List

Therapeutic Indications

Uses

Breast cancer

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.

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Breastfeeding
Pregnancy

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

Laboratory tests
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.

Diarrhoea
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.

P-gp substrates
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

Pregnancy

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.

Lactation

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.

Side Effects

Alanine aminotransferase increased
Allergic dermatitis
Aphthous ulcers
Arthralgia
Aspartate aminotransferase increased
Dermatitis acneiform
Diarrhoea
Dysaesthesia
Epistaxis
Erythema
Erythematous rash
Glossodynia
Hyperbilirubinaemia
Lip blister
Lip ulceration
Macular rash
Maculopapular rash
Mouth ulcers
Nausea
Oral pain
Oropharyngeal pain
Papular eruption
Pruritic rash
Pustular rash
Rash
Serum bilirubin increased
Skin exfoliation
Stomatitis
Tongue blistering
Tongue ulceration
Toxic skin reaction
Urticaria
Vomiting
Weight loss

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: December 2021

Reference Sources

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.