Drugs List

Therapeutic Indications

Uses

Combined with aromatase inhibitor for ErbB2 positive breast cancer
Combined with capecitabine for advanced/metastatic ErbB2 +ve breast cancer
Combined with trastuzumab in hormone receptor-negative breast cancer

In combination with capecitabine for the treatment of advanced or metastatic breast cancer for tumours that over express ErbB2 (HER2), following prior treatment with anthracyclines and taxanes and with trastuzumab in the metastatic setting.

In combination with trastuzumab for patients with hormone receptor negative metastatic disease that has progressed on prior trastuzumab therapy(ies) in combination with chemotherapy.

In combination with an aromatase inhibitor for postmenopausal women with hormone receptor positive metastatic breast cancer, not currently intended for chemotherapy.

Administration

Lapatinib should be taken either at least 1 hour before or at least 1 hour after food. To minimise variability to the patient administration should be standardised in relation to food intake.

Contraindications

Children under 18 years
Breastfeeding
Long QT syndrome
Pregnancy
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Electrolyte imbalance
History of torsade de pointes
Moderate hepatic impairment
Reduced left ventricular function
Severe renal impairment

Correct electrolyte disorders before treatment
Anti-diarrhoeals may be required during treatment
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of oral anti-cancer drugs
HER2 testing is mandatory prior to initiation of therapy
Measurement of LV ejection fraction recommended before and during treatment
Monitor ECG before, 1-2 weeks after treatment initiation and as indicated
Monitor hepatic function before initiating and at monthly intervals
Monitor for signs of pulmonary toxicity on long term therapy
Monitor serum electrolytes
Advise patient to report bowel dysfunction immediately
Advise patient to report skin reaction, pain, erythema, pruritus
Discontinue if pulmonary symptom grade 3 or worse occur
Discontinue treatment if Stevens-Johnson Syndrome suspected
Discontinue treatment if toxic epidermal necrolysis is suspected
Consider suspending treatment for any grade 2 or worse toxicity
Discontinue if severe hepatic changes occur
Discontinue permanently if grade 4 diarrhoea occurs
Interrupt treatment if diarrhoea grade 3 or grades 1 or 2 with complication
Suspend treatment if LVEF falls below 40%
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Female: Contraception required during and at least 5 days after treatment
Advise patient to avoid exposure to direct sunlight

Pregnancy and Lactation

Pregnancy

Contraindicated in pregnancy.

Animal studies have shown no teratogenic effects in rats or rabbits at 30, 60 and 120 mg/kg/day. There were minor foetal abnormalities and increased abortions in rats and rabbits at maternally toxic doses.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org )

Lactation

Lapatinib is contraindicated in breastfeeding.

Breastfeeding should be discontinued during and for 5 days after the last dose of lapatinib.

It is unknown whether lapatinib is excreted in human breast milk. In rats, growth retardation was observed in pups that were exposed to lapatinib via breast milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acne-like rash
Alopecia
Anaphylaxis
Anorexia
Arthralgia
Asthenia
Back pain
Cardiac failure
Constipation
Cough
Decreased ejection fraction
Dehydration
Diarrhoea
Dry skin
Dyspepsia
Dyspnoea
Epistaxis
Erythema multiforme
Extremity pain
Fatigue
Headache
Hepatotoxicity
Hot flushes
Hyperbilirubinaemia
Hypersensitivity reactions
Insomnia
Interstitial lung disease
Mucosal inflammation
Nail disorders
Nausea
Palmar-plantar erythrodysaesthesia
Palpitations
Paronychia
Pneumonitis
Pruritus
Pulmonary hypertension
Rash
Stevens-Johnson syndrome
Stomatitis
Toxic epidermal necrolysis
Vomiting

Presentation

Tablets containing lapatinib

Drugs List

Therapeutic Indications

Uses

Combined with aromatase inhibitor for ErbB2 positive breast cancer
Combined with capecitabine for advanced/metastatic ErbB2 +ve breast cancer
Combined with trastuzumab in hormone receptor-negative breast cancer

In combination with capecitabine for the treatment of advanced or metastatic breast cancer for tumours that over express ErbB2 (HER2), following prior treatment with anthracyclines and taxanes and with trastuzumab in the metastatic setting.

In combination with trastuzumab for patients with hormone receptor negative metastatic disease that has progressed on prior trastuzumab therapy(ies) in combination with chemotherapy.

In combination with an aromatase inhibitor for postmenopausal women with hormone receptor positive metastatic breast cancer, not currently intended for chemotherapy.

Dosage

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

Treatment should be initiated and supervised by physicians experienced in cancer chemotherapy.

The dose should not be divided.

Adults

Elderly

Additional Dosage Information

Administration

Lapatinib should be taken either at least 1 hour before or at least 1 hour after food. To minimise variability to the patient administration should be standardised in relation to food intake.

Contraindications

Children under 18 years
Breastfeeding
Long QT syndrome
Pregnancy
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Electrolyte imbalance
History of torsade de pointes
Moderate hepatic impairment
Reduced left ventricular function
Severe renal impairment

Correct electrolyte disorders before treatment
Anti-diarrhoeals may be required during treatment
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of oral anti-cancer drugs
HER2 testing is mandatory prior to initiation of therapy
Measurement of LV ejection fraction recommended before and during treatment
Monitor ECG before, 1-2 weeks after treatment initiation and as indicated
Monitor hepatic function before initiating and at monthly intervals
Monitor for signs of pulmonary toxicity on long term therapy
Monitor serum electrolytes
Advise patient to report bowel dysfunction immediately
Advise patient to report skin reaction, pain, erythema, pruritus
Discontinue if pulmonary symptom grade 3 or worse occur
Discontinue treatment if Stevens-Johnson Syndrome suspected
Discontinue treatment if toxic epidermal necrolysis is suspected
Consider suspending treatment for any grade 2 or worse toxicity
Discontinue if severe hepatic changes occur
Discontinue permanently if grade 4 diarrhoea occurs
Interrupt treatment if diarrhoea grade 3 or grades 1 or 2 with complication
Suspend treatment if LVEF falls below 40%
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Female: Contraception required during and at least 5 days after treatment
Advise patient to avoid exposure to direct sunlight

Pregnancy and Lactation

Pregnancy

Contraindicated in pregnancy.

Animal studies have shown no teratogenic effects in rats or rabbits at 30, 60 and 120 mg/kg/day. There were minor foetal abnormalities and increased abortions in rats and rabbits at maternally toxic doses.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org )

Lactation

Lapatinib is contraindicated in breastfeeding.

Breastfeeding should be discontinued during and for 5 days after the last dose of lapatinib.

It is unknown whether lapatinib is excreted in human breast milk. In rats, growth retardation was observed in pups that were exposed to lapatinib via breast milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acne-like rash
Alopecia
Anaphylaxis
Anorexia
Arthralgia
Asthenia
Back pain
Cardiac failure
Constipation
Cough
Decreased ejection fraction
Dehydration
Diarrhoea
Dry skin
Dyspepsia
Dyspnoea
Epistaxis
Erythema multiforme
Extremity pain
Fatigue
Headache
Hepatotoxicity
Hot flushes
Hyperbilirubinaemia
Hypersensitivity reactions
Insomnia
Interstitial lung disease
Mucosal inflammation
Nail disorders
Nausea
Palmar-plantar erythrodysaesthesia
Palpitations
Paronychia
Pneumonitis
Pruritus
Pulmonary hypertension
Rash
Stevens-Johnson syndrome
Stomatitis
Toxic epidermal necrolysis
Vomiting

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 2013

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 21 July 2015.

Summary of Product Characteristics: Tyverb 250mg tablets. GlaxoSmithKline UK. Revised May 2019.