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Lapatinib: Drug information

Lapatinib: Drug information
(For additional information see "Lapatinib: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US 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.

Brand Names: US
  • Tykerb
Brand Names: Canada
  • Tykerb
Pharmacologic Category
  • Antineoplastic Agent, Anti-HER2;
  • Antineoplastic Agent, Epidermal Growth Factor Receptor (EGFR) Inhibitor;
  • Antineoplastic Agent, Tyrosine Kinase Inhibitor
Dosing: Adult

Note: Correct electrolyte (eg, potassium, magnesium) abnormalities prior to and during treatment.

Breast cancer, advanced or metastatic, HER2+, after prior anthracycline, taxane, and trastuzumab therapy

Breast cancer, advanced or metastatic, HER2+, after 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

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 previously untreated brain metastases

Breast cancer, metastatic, HER2+, with previously untreated brain metastases (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

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+, salvage therapy

Breast cancer, metastatic, HER2+, HR+, salvage therapy (off-label combination): 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.

Colorectal cancer, metastatic, HER2+, with progression on conventional chemotherapy

Colorectal cancer, metastatic, HER2+, with progression on conventional chemotherapy (off-label use): Oral: 1,000 mg once daily (in combination with trastuzumab) until disease progression or unacceptable toxicity (Sartore-Bianchi 2016).

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: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, due to the minimal renal elimination (<2%), dosage adjustments may not be necessary.

Dosing: Hepatic Impairment: Adult

Mild or moderate preexisting impairment (Child-Pugh class A or B): There are no dosage adjustments provided in the manufacturer's labeling.

Severe preexisting impairment (Child-Pugh class C): The following adjustments should be considered (and are predicted to normalize the AUC), however, there are no clinical data associated with the adjustments; use with caution (due to increased lapatinib exposure).

In combination with capecitabine: Reduce dose from 1,250 mg once daily to 750 mg once daily.

In combination with letrozole: Reduce dose from 1,500 mg once daily to 1,000 mg once daily.

Severe hepatotoxicity during treatment: Discontinue lapatinib permanently (do not rechallenge).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

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 if life-threatening dermatologic reactions such as erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis (eg, progressive skin rash often with blisters or mucosal lesions) are suspected.

Diarrhea:

First unformed stool: Promptly administer antidiarrheal agents (eg, loperamide).

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.

Severe diarrhea: May require oral or IV fluids and electrolytes (and/or antibiotics if diarrhea is persistent beyond 24 hours, if with fever or grade 3 or 4 neutropenia).

Hypert ension: If indicated, initiate appropriate antihypertensive treatment to reduce the risk for cardiotoxicity (ASCO [Armenian 2017]).

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).

Dosage Forms: US

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

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Tykerb: 250 mg [contains polysorbate 80]

Administration: Adult

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.

Use: Labeled Indications

Breast cancer, advanced or metastatic: 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.

Use: Off-Label: Adult

Breast cancer, metastatic, HER2 overexpressing, with previously untreated brain metastases; Breast cancer, metastatic, HER2 overexpressing, with progression on prior trastuzumab-containing therapy; Colorectal cancer, metastatic, HER2 overexpressing, with progression on conventional chemotherapy

Medication Safety Issues
Sound-alike/look-alike issues:

Lapatinib may be confused with dasatinib, enasidenib, erlotinib, imatinib, larotrectinib, lenvatinib, lorlatinib, neratinib, regorafenib, SUNItinib, tucatinib, vandetanib.

Tykerb may be confused with Tukysa.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences reported for combination therapy with either capecitabine or letrozole in adults.

>10%:

Dermatologic: Alopecia (with letrozole: 13%), nail disease (with letrozole: 11%), palmar-plantar erythrodysesthesia (with capecitabine: 53%), pruritus (with letrozole: 12%), skin rash (with capecitabine: 28%; with letrozole: 44%), xeroderma (10% to 13%)

Gastrointestinal: Anorexia (with letrozole: 11%), diarrhea (64% to 65%; grades 3/4: ≤13%), dyspepsia (with capecitabine: 11%), nausea (with capecitabine: 44%; with letrozole: 31%; grade 3: ≤2%), stomatitis (with capecitabine: 14% to 15%), vomiting (17% to 26%; grades 3/4: ≤2%)

Hematologic & oncologic: Decreased hemoglobin (with capecitabine: 56%; grade 3: <1%), decreased neutrophils (with capecitabine: 22%; grades 3/4: ≤3%), decreased platelet count (with capecitabine: 18%; grade 3: <1%)

Hepatic: Increased serum alanine aminotransferase (37% to 46%), increased serum aspartate aminotransferase (49% to 53%), increased serum bilirubin (with letrozole: 22%; with capecitabine: 45%)

Nervous system: Asthenia (with letrozole: 12%), fatigue (with letrozole: 20%), headache (with letrozole: 14%)

Neuromuscular & skeletal: Back pain (with capecitabine: 11%), limb pain (with capecitabine: 12%)

Respiratory: Dyspnea (with capecitabine: 12%), epistaxis (with letrozole: 11%)

1% to 10%:

Cardiovascular: Decreased left ventricular ejection fraction (with letrozole: 4%, grades 3/4: <1%; with capecitabine: grade 2: 2%, grade 3: <1%)

Nervous system: Insomnia (with capecitabine: 10%)

<1%: Hepatic: Hepatotoxicity

Frequency not defined: Respiratory: Interstitial pulmonary disease, pneumonitis

Postmarketing:

Cardiovascular: Prolonged QT interval on ECG, torsades de pointes, ventricular arrhythmia

Dermatologic: Paronychia, skin fissure, Stevens-Johnson syndrome, toxic epidermal necrolysis

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Contraindications

Known severe hypersensitivity (eg, anaphylaxis) to lapatinib or any component of the formulation

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. 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]).

• Dermatologic toxicity: Severe cutaneous reactions have been reported with lapatinib.

• 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.

• Hepatotoxicity: 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.

• Pulmonary toxicity: Interstitial lung disease (ILD) and pneumonitis have been reported (with lapatinib monotherapy and combination chemotherapy). Pulmonary symptoms indicative of ILD or pneumonitis include dyspnea and 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).

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.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, CYP3A4 (weak), P-glycoprotein/ABCB1

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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. Risk D: Consider therapy modification

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: 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. Risk D: Consider therapy modification

ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy

Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: 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. Risk D: Consider therapy modification

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: 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. Risk D: Consider therapy modification

CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP2C8 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Lapatinib may increase the serum concentration of CYP2C8 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Lapatinib. Risk C: 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. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Lapatinib. Risk C: 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, a reduced lapatinib dose of 500 mg daily should be considered. The previous lapatinib dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: 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. Risk X: Avoid combination

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. Risk D: Consider therapy modification

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy

Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy

Grapefruit Juice: May increase the serum concentration of Lapatinib. Risk X: Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: 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. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification

Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy

Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Lapatinib. Risk C: Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: 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. Risk C: Monitor therapy

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy

Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification

Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification

RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy

RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy

Rosuvastatin: BCRP/ABCG2 Inhibitors may increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy

Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy

Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). 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. Risk D: Consider therapy modification

Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination

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. Risk X: Avoid combination

Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy

Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Risk C: Monitor therapy

Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy

Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy

Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy

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. Risk D: 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. Risk D: Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination

Food Interactions

Systemic exposure of lapatinib is increased when administered with food (AUC three- to fourfold higher). Grapefruit juice may increase the levels/effects of lapatinib. Management: Administer once daily on an empty stomach, 1 hour before or 1 hour after a meal at the same time each day. Avoid grapefruit juice. Maintain adequate hydration, unless instructed to restrict fluid intake.

Reproductive Considerations

Pregnancy status should be determined prior to initiation of lapatinib. Patients who could become pregnant and patients with partners who could become pregnant 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]).

Breastfeeding Considerations

It is not known if lapatinib is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends discontinuing breastfeeding during treatment with lapatinib and for 1 week after the last lapatinib dose.

Dietary Considerations

Avoid grapefruit juice.

Monitoring Parameters

CBC with differential, LFT, including transaminases, bilirubin, and alkaline phosphatase (baseline and every 4 to 6 weeks during treatment and as clinically indicated); electrolytes, including potassium and magnesium. Monitor left ventricular ejection fraction (baseline and periodic), ECG monitoring if at risk for QTc prolongation. Evaluate pregnancy status prior to treatment in patients who could become pregnant. Monitor BP routinely during lapatinib treatment (ASCO [Armenian 2017]). Monitor for fluid retention and signs/symptoms of ILD or pneumonitis, diarrhea (instruct patients to report any changes in bowel habits immediately; early identification and intervention is critical for optimal management), and dermatologic toxicity. Monitor adherence.

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, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen 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.

Mechanism of Action

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.

Pharmacokinetics

Absorption: Incomplete and variable

Protein binding: >99% to albumin and alpha1-acid glycoprotein

Metabolism: Hepatic; extensive via CYP3A4 and 3A5, and to a lesser extent via CYP2C19 and 2C8 to oxidized metabolites

Half-life elimination: ~24 hours

Time to peak, plasma: ~4 hours (Burris 2009)

Excretion: Feces (27% as unchanged drug; range 3% to 67%); urine (<2%)

Pharmacokinetics: Additional Considerations

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.

Pricing: US

Tablets (Lapatinib Ditosylate Oral)

250 mg (per each): $60.14

Tablets (Tykerb Oral)

250 mg (per each): $70.17

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Brand Names: International
  • Tykerb (AE, AR, AU, BB, BH, BR, CL, CO, CR, DO, EG, HK, HN, ID, IL, IN, JO, JP, KR, KW, LB, LK, MY, NZ, PA, PE, PH, QA, SA, SG, SV, TH, TW, UY);
  • Tyverb (AT, BE, CH, CY, CZ, DE, DK, EE, ES, FR, GB, GR, HR, IE, IS, IT, LT, LU, LV, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR, UA)


For country abbreviations used in Lexicomp (show table)
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  2. Bachelot T, Romieu G, Campone M, et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study. Lancet Oncol. 2013;14(1):64-71. doi:10.1016/S1470-2045(12)70432-1 [PubMed 23122784]
  3. Baselga J, Bradbury I, Eidtmann H, et al, “Lapatinib With Trastuzumab for HER2-Positive Early Breast Cancer (NeoALTTO): A Randomised, Open-Label, Multicentre, Phase 3 Trial,” Lancet, 2012, 379(9816):633-40. [PubMed 22257673]
  4. Blackwell KL, Burstein HJ, Storniolo AM, et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 study. J Clin Oncol. 2012;30(21):2585-2592. doi:10.1200/JCO.2011.35.6725 [PubMed 22689807]
  5. Blackwell KL, Burstein HJ, Storniolo AM, et al. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010;28(7):1124-1130. doi:10.1200/JCO.2008.21.4437 [PubMed 20124187]
  6. Burris HA 3rd, Taylor CW, Jones SF, et al, “A Phase I and Pharmacokinetic Study of Oral Lapatinib Administered Once or Twice Daily in Patients With Solid Malignancies,” Clin Cancer Res, 2009, 15(21):6702-8. [PubMed 19825948]
  7. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355(26):2733-2743. doi:10.1056/NEJMoa064320 [PubMed 17192538]
  8. Giordano SH, Temin S, Chandarlapaty S, et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018;36(26):2736-2740. doi:10.1200/JCO.2018.79.2697 [PubMed 29939838]
  9. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. Published online July 27, 2020. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  10. Johnston S, Pippen J Jr, Pivot X, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009;27(33):5538-5546. doi:10.1200/JCO.2009.23.3734 [PubMed 19786658]
  11. Johnston SRD, Hegg R, Im SA, et al. Phase III, randomized study of dual human epidermal growth factor receptor 2 (HER2) blockade with lapatinib plus trastuzumab in combination with an aromatase inhibitor in postmenopausal women with HER2-positive, hormone receptor-positive metastatic breast cancer: updated results of ALTERNATIVE. J Clin Oncol. Published online August 21, 2020. doi:10.1200/JCO.20.01894 [PubMed 32822287]
  12. Kelly H, Graham M, Humes E, et al. Delivery of a healthy baby after first-trimester maternal exposure to lapatinib. Clin Breast Cancer. 2006;7(4):339-341. doi:10.3816/CBC.2006.n.048 [PubMed 17092403]
  13. Lambertini M, Martel S, Campbell C, et al. Pregnancies during and after trastuzumab and/or lapatinib in patients with human epidermal growth factor receptor 2-positive early breast cancer: analysis from the NeoALTTO (BIG 1-06) and ALTTO (BIG 2-06) trials. Cancer. 2019;125(2):307-316. doi:10.1002/cncr.31784 [PubMed 30335191]
  14. 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. [PubMed 27543577]
  15. Page RL 2nd, O'Bryant CL, Cheng D, et al; American Heart Association Clinical Pharmacology and Heart Failure and Transplantation Committees of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association [published correction appears in Circulation. 2016;134(12):e261]. Circulation. 2016;134(6):e32-e69. [PubMed 27400984]
  16. Peccatori FA, Azim HA Jr, Orecchia R, et al; ESMO Guidelines Working Group. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(suppl 6):vi160-170. [PubMed 23813932]
  17. Ramakrishna N, Temin S, Chandarlapaty S, et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: ASCO clinical practice guideline update. J Clin Oncol. 2018;36(27):2804-2807. doi:10.1200/JCO.2018.79.2713 [PubMed 29939840]
  18. Sartore-Bianchi A, Trusolino L, Martino C, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016;17(6):738-746. doi:10.1016/S1470-2045(16)00150-9 [PubMed 27108243]
  19. Sharma A, Nguyen HS, Lozen A, Sharma A, Mueller W. Brain metastases from breast cancer during pregnancy. Surg Neurol Int. 2016;7(suppl 23):S603-S606. doi:10.4103/2152-7806.189730 [PubMed 27656319]
  20. Tykerb (lapatinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; February 2021.
  21. Tykerb (lapatinib) [product monograph]. Dorval, Quebec, Canada: Novartis Pharmaceuticals Canada Inc; March 2022.
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