Lapatinib
Medically reviewed by Drugs.com. Last updated on May 24, 2020.
Pronunciation
(la PA ti nib)
Index Terms
- GW572016
- Lapatinib Ditosylate
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Tykerb: 250 mg [contains fd&c yellow #6 (sunset yellow), fd&c yellow #6 aluminum lake]
Generic: 250 mg
Brand Names: U.S.
- Tykerb
Pharmacologic Category
- Antineoplastic Agent, Anti-HER2
- Antineoplastic Agent, Epidermal Growth Factor Receptor (EGFR) Inhibitor
- Antineoplastic Agent, Tyrosine Kinase Inhibitor
Pharmacology
Tyrosine kinase (dual kinase) inhibitor; inhibits EGFR (ErbB1) and HER2 (ErbB2) by reversibly binding to tyrosine kinase, blocking phosphorylation and activation of downstream second messengers (Erk1/2 and Akt), regulating cellular proliferation and survival in ErbB- and ErbB2-expressing tumors. Combination therapy with lapatinib and endocrine therapy may overcome endocrine resistance occurring in HER2+ and hormone receptor positive disease.
Absorption
Incomplete and variable
Metabolism
Hepatic; extensive via CYP3A4 and 3A5, and to a lesser extent via CYP2C19 and 2C8 to oxidized metabolites
Excretion
Feces (27% as unchanged drug; range 3% to 67%); urine (<2%)
Time to Peak
~4 hours (Burris 2009)
Half-Life Elimination
~24 hours
Protein Binding
>99% to albumin and alpha1-acid glycoprotein
Special Populations: Hepatic Function Impairment
AUC increased (after a single 100 mg oral dose) by ~14% and 63% in patients with moderate (Child-Pugh class B) and severe (Child-Pugh class C) hepatic impairment, respectively.
Use: Labeled Indications
Breast cancer: Treatment of human epidermal growth receptor type 2 (HER2) overexpressing advanced or metastatic breast cancer (in combination with capecitabine) in patients who have received prior therapy (with an anthracycline, a taxane, and trastuzumab); HER2 overexpressing hormone receptor-positive metastatic breast cancer in postmenopausal women where hormone therapy is indicated (in combination with letrozole)
Limitations of use: Patients should have disease progression on trastuzumab prior to initiation of treatment with lapatinib in combination with capecitabine.
Off Label Uses
HER2 overexpressing metastatic breast cancer (in combination with trastuzumab) with progression on prior trastuzumab-containing therapy
Data from a phase 3 randomized, controlled study support the use of lapatinib in combination with trastuzumab in the management of metastatic breast cancer that has progressed on prior trastuzumab therapy [Blackwell 2012].
Based on the American Society of Clinical Oncology (ASCO) guidelines for systemic therapy for advanced HER2-positive breast cancer, lapatinib in combination with trastuzumab is a third-line treatment option in patients whose disease has progressed during or after second-line or greater HER2-targeted therapy and have already received pertuzumab and ado-trastuzumab emtansine [ASCO [Giordano 2018]].
HER2 overexpressing metastatic breast cancer with brain metastases (in combination with capecitabine)
Data from a small phase 2 study support the use of lapatinib in combination with capecitabine in the management of HER2-positive metastatic breast cancer with brain metastases [Bachelot 2013].
ASCO guidelines for disease management in patients with advanced HER2-positive breast cancer and brain metastases suggest lapatinib plus capecitabine as a systemic treatment option for patients with low-volume brain metastases and who have not received radiation therapy [ASCO [Ramakrishna 2018]].
Contraindications
Known severe hypersensitivity (eg, anaphylaxis) to lapatinib or any component of the formulation
Dosing: Adult
Breast cancer, metastatic, HER2+ (with prior anthracycline, taxane, and trastuzumab therapy): Oral: 1,250 mg once daily (in combination with capecitabine) until disease progression or unacceptable toxicity (Geyer 2006)
Breast cancer, metastatic, HER2+, hormonal therapy indicated: Oral: 1,500 mg once daily (in combination with letrozole) until disease progression (Johnston 2009)
Breast cancer, metastatic, HER2+ with brain metastases, first-line therapy (off-label use): Oral: 1,250 mg once daily (in combination with capecitabine) until disease progression or unacceptable toxicity (Bachelot 2013)
Breast cancer, metastatic, HER2+, with progression on prior trastuzumab therapy (off-label use): Oral: 1,000 mg once daily (in combination with trastuzumab) (Blackwell 2010; Blackwell 2012)
Breast cancer, metastatic, HER2+, HR+ (off-label combination; salvage therapy): Oral: 1,000 mg once daily (in combination with trastuzumab and an aromatase inhibitor) until disease progression or unacceptable toxicity (Johnston 2020). Note: Patients in the study had received prior endocrine therapy and had disease progression during or after a prior regimen containing trastuzumab plus chemotherapy in the neo(adjuvant) setting and/or first-line metastatic setting.
Missed doses: If a dose is missed, resume with the next scheduled daily dose; do not double the dose the next day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Adjustment for Toxicity
Cardiac toxicity: Discontinue lapatinib treatment for at least 2 weeks for left ventricular ejection fraction (LVEF) < LLN or decreased LVEF ≥ grade 2; lapatinib may be restarted at 1,000 mg once daily (in combination with capecitabine) or 1,250 mg once daily (in combination with letrozole) if LVEF recovers to normal and patient is asymptomatic.
Dermatologic toxicity: Discontinue lapatinib treatment for suspected erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis.
Diarrhea:
Grade 3 diarrhea or grade 1 or 2 diarrhea with complicating features (moderate to severe abdominal cramping, ≥ grade 2 nausea/vomiting, decreased performance status, fever, sepsis, neutropenia, frank bleeding, or dehydration): Interrupt lapatinib treatment; may restart lapatinib at a reduced dose (from 1,500 mg once daily to 1,250 mg once daily or from 1,250 mg once daily to 1,000 mg once daily) when diarrhea resolves to ≤ grade 1.
Grade 4 diarrhea: Permanently discontinue lapatinib.
Pulmonary toxicity: Discontinue lapatinib treatment with pulmonary symptoms indicative of interstitial lung disease or pneumonitis that are ≥ grade 3.
Other toxicities: Withhold lapatinib for any toxicity (other than cardiac) ≥ grade 2 until toxicity resolves to ≤ grade 1 and reinitiate lapatinib at the standard dose of 1,250 or 1,500 mg once daily; for persistent toxicity, reduce lapatinib dosage to 1,000 mg once daily (in combination with capecitabine) or 1,250 mg once daily (in combination with letrozole).
Extemporaneously Prepared
A 50 mg/mL oral suspension may be prepared using lapatinib 250 mg tablets and Ora-Plus:Ora-Sweet (1:1 vehicle). Determine necessary quantity of lapatinib 250 mg tablets; crush the tablets in a glass mortar and triturate to a fine powder (estimated powder volume for each lapatinib 250 mg tablet is 0.6 mL). Measure the necessary volume of Ora-Plus and add to the powder by geometric dilution until a smooth suspension is created. Measure the necessary volume of Ora-Sweet and add to the suspension. Transfer to an amber plastic bottle and label “Shake Well Before Use”, “Do Not Refrigerate” and “Use by (date)”. Suspension is stable for at least 28 days at room temperature; do not refrigerate due to potential for increased viscosity.
Li Q, Liu Z, Kolli S, et al. Stability of extemporaneous erlotinib, lapatinib, and imatinib oral suspension. Am J Health Syst Pharm. 2016;73(17):1331-1337.27543577Administration
Oral: Administer on an empty stomach, 1 hour before or 1 hour after a meal. Administer the full dose once a day (tablets administered all at once); dividing dose throughout the day is not recommended.
Note: For combination treatment with capecitabine, capecitabine should be administered in 2 doses (approximately 12 hours apart) and taken with food or within 30 minutes after a meal.
Dietary Considerations
Avoid grapefruit juice.
Storage
Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).
An oral suspension (50 mg/mL) prepared using lapatinib 250 mg tablets and Ora-Plus:Ora-Sweet (1:1 vehicle) is stable for at least 28 days at room temperature; do not refrigerate due to potential increased viscosity (Li 2016).
Drug Interactions
Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Consider therapy modification
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Monitor therapy
Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Consider therapy modification
Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-gp inhibitor. Avoid concomitant use of betrixaban and P-gp inhibitors in patients with severe renal impairment (CrCL less than 30 mL/min). Consider therapy modification
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Avoid combination
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Monitor therapy
Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Consider therapy modification
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a P-gp inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Lapatinib. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Lapatinib. Management: If concomitant use cannot be avoided, titrate lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Lapatinib. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Lapatinib. Management: Avoid use of lapatinib and strong CYP3A4 inhibitors when possible. If combined, reduce lapatinib dose to 500 mg daily. The previous lapatinib dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to concomitant therapy when possible. If concomitant therapy cannot be avoided, monitor for reduced clinical effects of the CYP3A4 substrate. Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
DexAMETHasone (Systemic): May decrease the serum concentration of Lapatinib. Management: If therapy overlap cannot be avoided, consider titrating lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Avoid combination
Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digitoxin. Monitor therapy
Digoxin: Lapatinib may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with lapatinib. Reduce digoxin concentrations by either reducing the digoxin dose by 30% to 50% or by modifying the dosing frequency. Consider therapy modification
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Avoid combination
Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Monitor therapy
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy
Grapefruit Juice: May increase the serum concentration of Lapatinib. Avoid combination
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Monitor therapy
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Consider therapy modification
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Monitor therapy
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy
Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy
Ozanimod: BCRP/ABCG2 Inhibitors may increase serum concentrations of the active metabolite(s) of Ozanimod. Avoid combination
Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Lapatinib. Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Avoid combination
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Monitor therapy
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Monitor therapy
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Sirolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus. Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Consider therapy modification
St John's Wort: May decrease the serum concentration of Lapatinib. Management: If therapy overlap cannot be avoided, consider titrating lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Avoid combination
Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy
Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy
Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Monitor therapy
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Tolvaptan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tolvaptan. Monitor therapy
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Consider therapy modification
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Consider therapy modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
Adverse Reactions
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Percentages reported for combination therapy.
>10%:
Central nervous system: Fatigue (≤20%), headache (14%)
Dermatologic: Palmar-plantar erythrodysesthesia (with capecitabine: 53%), skin rash (28% to 44%), alopecia (13%), xeroderma (10% to 13%), pruritus (12%), nail disease (11%)
Gastrointestinal: Diarrhea (64% to 65%), nausea (31% to 44%), vomiting (17% to 26%), mucositis (15%), stomatitis (14%), anorexia (11%), dyspepsia (11%)
Hematologic & oncologic: Decreased hemoglobin (with capecitabine: 56%; grade 3: <1%), decreased neutrophils (with capecitabine: 22%; grade 3: 3%; grade 4: <1%), decreased platelet count (with capecitabine: 18%; grade 3: <1%)
Hepatic: Increased serum aspartate aminotransferase (49% to 53%), increased serum alanine aminotransferase (37% to 46%), increased serum bilirubin (22% to 45%)
Neuromuscular & skeletal: Asthenia (12%), limb pain (12%), back pain (11%)
Respiratory: Dyspnea (12%), epistaxis (11%)
1% to 10%:
Cardiovascular: Decreased left ventricular ejection fraction (with letrozole: 5%; with capecitabine: grade 2: 2%; grade 3: <1%)
Central nervous system: Insomnia (10%)
<1%, postmarketing, and/or case reports: Anaphylaxis, hepatotoxicity, hypersensitivity reaction, interstitial pulmonary disease, paronychia, pneumonitis, prolonged QT interval on ECG, severe dermatological reaction, Stevens-Johnson syndrome, torsades de pointes, toxic epidermal necrolysis, ventricular arrhythmia
ALERT: U.S. Boxed Warning
Hepatotoxicity:Hepatotoxicity has been observed in clinical trials and postmarketing experience. The hepatotoxicity may be severe, and deaths have been reported. Causality of the deaths is uncertain.
Warnings/Precautions
Concerns related to adverse effects:
• Cardiotoxicity: Decreases in left ventricular ejection fraction (LVEF) have been reported (usually within the first 3 months of treatment); baseline and periodic LVEF evaluations are recommended. Interrupt treatment with decreased LVEF ≥ grade 2 or LVEF < LLN; may reinitiate with a reduced dose after a minimum of 2 weeks if the LVEF recovers and the patient is asymptomatic. Use with caution in conditions that may impair left ventricular function and in patients with a history of or predisposed to (prior treatment with anthracyclines, chest wall irradiation) left ventricular dysfunction. In a scientific statement from the American Heart Association, lapatinib has been determined to be an agent that may either cause reversible direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate/major) (AHA [Page 2016]). Monitor BP routinely during lapatinib treatment; if indicated, initiate appropriate antihypertensive treatment to reduce the risk for cardiotoxicity (ASCO [Armenian 2017]).
• Dermatologic toxicity: Severe cutaneous reactions have been reported with use. Discontinue therapy if life-threatening dermatologic reactions (eg, progressive skin rash with blisters or mucosal lesions) such as erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis occur.
• Diarrhea: Diarrhea is common (onset is generally within 6 days and duration is 4 to 5 days); may be severe and/or fatal. Diarrhea is best managed with early intervention; instruct patients to immediately report any bowel pattern changes. After first unformed stool, administer antidiarrheal agents; severe diarrhea may require hydration, electrolytes, antibiotics (if duration >24 hours, fever, or grade 3/4 neutropenia), and/or treatment interruption, dose reduction, or discontinuation.
• Hepatitis B virus reactivation: The American Society of Clinical Oncology hepatitis B screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends hepatitis B virus (HBV) screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow up.
• Hepatotoxicity: [US Boxed Warning]: Hepatotoxicity has been observed in clinical trials and postmarketing experience. Hepatotoxicity may be severe; deaths have been reported (causality of the deaths is uncertain). ALT or AST elevations >3 times ULN and total bilirubin >2 times ULN have been reported. Onset may occur within days to several months after treatment initiation. Monitor transaminases, bilirubin, and alkaline phosphatase (at baseline and every 4 to 6 weeks during treatment, and as clinically indicated); discontinue with severe changes in liver function during treatment; do not reinitiate.
• Pulmonary toxicity: Interstitial lung disease (ILD) and pneumonitis have been reported (with lapatinib monotherapy and combination chemotherapy); monitor for pulmonary symptoms that may indicate ILD or pneumonitis; discontinue treatment for grade 3 (or higher) pulmonary symptoms indicative of ILD or pneumonitis (eg, dyspnea, dry cough).
• QT prolongation: Concentration-dependent QT prolongation has been observed with lapatinib. Monitor patients who have or may develop QT prolongation during treatment (eg, hypokalemia or hypomagnesemia, congenital long QT syndrome, patients taking antiarrhythmics or other medications known to prolong the QT interval, cumulative high-dose anthracycline therapy). Correct electrolyte (potassium, calcium, and magnesium) abnormalities prior to and during treatment.
Disease related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; dose reductions should be considered in patients with preexisting severe (Child-Pugh class C) hepatic impairment.
Special populations:
• Pharmacogenomics: Patients who carry the HLA alleles DQA1*02:01 and DRB1*07:01 may experience a greater incidence of severe liver injury than patients who are noncarriers. These alleles are present in ~15% to 25% of Caucasian, Asian, African, and Hispanic patient populations and 1% in Japanese populations.
Monitoring Parameters
CBC with differential, LFT, including transaminases, bilirubin, and alkaline phosphatase (baseline and every 4 to 6 weeks during treatment); electrolytes, including calcium, potassium, magnesium. Hepatitis B virus screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning systemic anticancer therapy (ASCO [Hwang 2020]). Monitor left ventricular ejection fraction (baseline and periodic), ECG monitoring if at risk for QTc prolongation. Evaluate pregnancy status in females of reproductive potential prior to therapy. Monitor for fluid retention and signs/symptoms of ILD or pneumonitis, diarrhea, and dermatologic toxicity. Monitor adherence.
Reproductive Considerations
Pregnancy status should be determined prior to initiation of lapatinib. Females of reproductive potential and male patients with female partners of reproductive potential should be advised to use effective contraception during treatment and for 1 week after the last lapatinib dose.
Pregnancy Considerations
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to lapatinib may cause fetal harm. Outcome information following maternal use of lapatinib during pregnancy or pregnancies that occurred following completion of lapatinib therapy is limited (Kelly 2006; Lambertini 2019; Sharma 2016).
European Society for Medical Oncology guidelines for cancer during pregnancy recommend delaying treatment with HER-2 targeted agents until after delivery in pregnant patients with HER-2 positive disease (ESMO [Peccatori 2013]).
Patient Education
What is this drug used for?
• It is used to treat breast cancer.
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
• Dry skin
• Itching
• Headache
• Hair loss
• Back pain
• Nosebleed
• Nail changes
• Mouth sores
• Mouth irritation
• Loss of strength and energy
• Lack of appetite
• Painful extremities
• Trouble sleeping
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin
• Lung problems like shortness of breath or other trouble breathing, cough that is new or worse
• Shortness of breath
• Excessive weight gain
• Swelling of arms or legs
• Abnormal heartbeat
• Fast heartbeat
• Dizziness
• Passing out
• Severe abdominal pain
• Severe diarrhea
• Diarrhea with abdominal cramps
• Severe nausea
• Vomiting
• Fever
• Fluid loss
• Redness of irritation on palms or soles of feet
• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
More about lapatinib
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- Drug class: EGFR inhibitors
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Other brands: Tykerb