Version May 2024
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.
Note: Correct electrolyte (eg, potassium, magnesium) abnormalities prior to and during treatment. Actively manage modifiable cardiac risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) before initiating treatment (ASCO [Armenian 2017]).
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: Oral: 1,500 mg once daily (in combination with letrozole) until disease progression (Johnston 2009).
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 (off-label use): Oral: 1,000 mg once daily (in combination with trastuzumab) (Blackwell 2010; Blackwell 2012).
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 (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.
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.
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).
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.
Asymptomatic heart disease: Consider initiating heart failure medications (eg, angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker, and/or beta-blockers) in patients with asymptomatic (stage B) heart disease (ASCO [Armenian 2017], ESC [Lyon 2022]).
Mild cardiac dysfunction: Continue treatment with close cardiovascular monitoring (ESC [Lyon 2022]).
Moderate cardiac dysfunction: Consider continuing treatment with close cardiovascular monitoring. Initiation of heart failure medications is recommended (ESC [Lyon 2022]).
Severe cardiac dysfunction: Interrupt treatment and utilize a multidisciplinary approach when deciding if/when to restart. Initiation of heart failure medications is recommended (ESC [Lyon 2022]).
Symptomatic heart disease: Initiate heart failure medications (ESC [Lyon 2022]).
Mild cardiac dysfunction: Consider a multidisciplinary approach for decisions regarding treatment interruption versus continuation (ESC [Lyon 2022]).
Moderate or severe cardiac dysfunction: Interrupt treatment; consider a multidisciplinary approach for decisions regarding treatment reinitiation (ESC [Lyon 2022]).
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).
Refer to adult dosing.
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
Known severe hypersensitivity (eg, anaphylaxis) to lapatinib or any component of the formulation.
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.
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
Yes
Tablets (Lapatinib Ditosylate Oral)
250 mg (per each): $60.14
Tablets (Tykerb Oral)
250 mg (per each): $79.43
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Tykerb: 250 mg [contains polysorbate 80]
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.
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.
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
Lapatinib may be confused with dasatinib, enasidenib, erlotinib, imatinib, larotrectinib, lenvatinib, lorlatinib, neratinib, regorafenib, SUNItinib, tucatinib, vandetanib.
Tykerb may be confused with Tukysa.
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.
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
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: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. 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
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification
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
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
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 (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). 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
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.
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.
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]).
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.
Avoid grapefruit juice.
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.
Additional cardiovascular monitoring (guideline recommendations): Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017], ESC [Lyon 2022]). Obtain a baseline echocardiography (transthoracic preferred) and repeat every 3 months during treatment (may reduce to every 4 to 6 months if normal and asymptomatic), assess more frequently if clinically indicated and obtain echocardiography within 12 months after completion; in high- and very high-risk patients, assess troponin and natriuretic peptide at baseline and consider assessing every 2 to 3 cycles, and at 3 and 12 months after completion of therapy; in low- and moderate-risk patients, consider troponin and natriuretic peptide at baseline (post-anthracycline), every 3 months and 12 months after completion of therapy (ESC [Lyon 2022]).
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.
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
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%)
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.
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