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Erlotinib: Drug information

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

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Tarceva
Brand Names: Canada
  • APO-Erlotinib;
  • NAT-Erlotinib;
  • PMS-Erlotinib;
  • Tarceva;
  • TEVA-Erlotinib
Pharmacologic Category
  • Antineoplastic Agent, Epidermal Growth Factor Receptor (EGFR) Inhibitor;
  • Antineoplastic Agent, Tyrosine Kinase Inhibitor
Dosing: Adult
Non–small cell lung cancer, metastatic, in patients with epidermal growth factor receptor exon 19 deletions or exon 21 substitution mutations

Non–small cell lung cancer, metastatic, in patients with epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations (as first-line therapy, maintenance treatment, or for progressive disease): Oral: 150 mg once daily until disease progression or unacceptable toxicity (Cappuzzo 2010; Rosell 2012; Shepherd 2005).

Off-label combinations:

First-line treatment, advanced disease: Oral: 150 mg once daily (in combination with ramucirumab) until disease progression or unacceptable toxicity (Nakagawa 2019).

Nonsquamous non–small cell lung cancer (advanced or recurrent disease): Oral: 150 mg once daily (in combination with bevacizumab) until disease progression or unacceptable toxicity (Saito 2019).

Pancreatic cancer, locally advanced, unresectable or metastatic

Pancreatic cancer, locally advanced, unresectable or metastatic: Oral: 100 mg once daily (in combination with gemcitabine); continue until disease progression or unacceptable toxicity (Moore 2007).

Renal cell carcinoma, papillary

Renal cell carcinoma, papillary (advanced) (off-label use): Oral: 150 mg once daily (in combination with bevacizumab) until disease progression or unacceptable toxicity (Srinivasan 2014) or 150 mg once daily (as monotherapy) until disease progression or unacceptable toxicity (Gordon 2009).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosage adjustment for concomitant smoking: Avoid tobacco smoking if possible. If unavoidable, increase erlotinib dose at 2-week intervals in 50 mg increments to a maximum dose of 300 mg (with careful monitoring); immediately reduce erlotinib dose to recommended starting dose (based on indication) upon smoking cessation.

Dosing: Kidney Impairment: Adult

Renal impairment at treatment initiation: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied), although ~8% of a single dose is excreted in the urine.

Renal toxicity during treatment:

Grades 3/4 renal toxicity: Withhold erlotinib and consider discontinuing. If erlotinib is resumed, reinitiate with a 50 mg dose reduction after toxicity has resolved to baseline or ≤ grade 1.

Renal failure associated with hepatorenal syndrome or due to dehydration: Withhold erlotinib until renal toxicity is resolved. If erlotinib is resumed, reinitiate with a 50 mg dose reduction after toxicity has resolved.

Dosing: Hepatic Impairment: Adult

Hepatic impairment at treatment initiation:

Total bilirubin > ULN or Child-Pugh classes A, B, and C: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution and monitor closely during treatment.

Total bilirubin >3 times ULN: Use extreme caution.

The following adjustments have also been studied: A reduced starting dose (75 mg once daily) has been recommended in patients with hepatic dysfunction (AST ≥3 times ULN or direct bilirubin 1 to 7 mg/dL), with individualized dosage escalation if tolerated (Miller 2007); another study determined that pharmacokinetic and safety profiles were similar between patients with normal hepatic function and moderate hepatic impairment (O’Bryant 2012).

Hepatotoxicity during treatment:

Patients with normal hepatic function at baseline: If total bilirubin >3 times ULN or transaminases >5 times ULN: Interrupt erlotinib and consider discontinuing. If erlotinib is resumed, reinitiate with a 50 mg dose reduction after bilirubin and transaminases return to baseline or ≤ grade 1. Discontinue if hepatotoxicity does not improve within 3 weeks.

Patients with baseline hepatic impairment or biliary obstruction: If bilirubin doubles or transaminases triple over baseline: Interrupt erlotinib and consider discontinuing. If erlotinib is resumed, reinitiate with a 50 mg dose reduction after bilirubin and transaminases return to baseline or ≤ grade 1. Discontinue if hepatotoxicity does not improve within 3 weeks.

Severe hepatotoxicity that does not significantly improve or resolve within 3 weeks: Discontinue erlotinib.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

Dermatologic toxicity: Note: Management of skin rashes that are not serious should include alcohol-free lotions, topical antibiotics, or topical corticosteroids, or if necessary, oral antibiotics and systemic corticosteroids; avoid exposure to sunlight (Kiyohara 2013).

Bullous, blistering, or exfoliative skin toxicity (severe): Discontinue erlotinib.

Severe rash (unresponsive to medical management): Withhold erlotinib; may reinitiate with a 50 mg dose reduction after toxicity has resolved to baseline or ≤ grade 1.

GI toxicity:

Diarrhea: Manage with loperamide; in persistent, severe diarrhea (unresponsive to loperamide) or dehydration due to diarrhea, withhold erlotinib; may reinitiate with a 50 mg dose reduction after toxicity has resolved to baseline or ≤ grade 1.

GI perforation: Discontinue erlotinib.

Ocular toxicities:

Acute or worsening ocular toxicities (eg, eye pain): Interrupt erlotinib and consider discontinuing. If erlotinib is resumed, reinitiate with a 50 mg dose reduction after toxicity has resolved to baseline or ≤ grade 1.

Corneal perforation or severe ulceration: Discontinue erlotinib.

Keratitis (grade 3 or 4 or grade 2 persisting >2 weeks): Withhold erlotinib; may reinitiate with a 50 mg dose reduction after toxicity has resolved to baseline or ≤ grade 1.

Pulmonary symptoms: Acute onset (or worsening) of pulmonary symptoms (eg, dyspnea, cough, fever): Withhold erlotinib while evaluating for drug-induced interstitial lung disease; if resuming erlotinib, reinitiate with a 50 mg dose reduction after symptoms resolve to ≤ grade 1 or baseline. Discontinue erlotinib permanently with development/confirmation of interstitial lung disease.

Dosage Forms: US

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

Tablet, Oral, as hydrochloride:

Tarceva: 25 mg [contains fd&c yellow #6 (sunset yellow)]

Tarceva: 100 mg, 150 mg

Generic: 25 mg, 100 mg, 150 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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

Tablet, Oral, as hydrochloride:

Tarceva: 25 mg, 100 mg, 150 mg

Generic: 25 mg, 100 mg, 150 mg

Administration: Adult

Oral: The manufacturer recommends administration on an empty stomach (at least 1 hour before or 2 hours after the ingestion of food).

Acid-reducing agents: Avoid concomitant use with proton pump inhibitors (if possible). If taken with an H2-receptor antagonist, administer erlotinib 10 hours after the H2-receptor antagonist dose and ≥2 hours prior to the next H2- receptor dose. If an antacid is necessary, separate dosing by several hours.

If necessary, an oral suspension may be prepared if patients are unable to swallow tablets whole (see Extemporaneously Prepared).

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Non–small cell lung cancer, metastatic: Treatment of metastatic non–small cell lung cancer (NSCLC) in tumors with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an approved test either as first-line, maintenance, or as second or greater line treatment after progression following at least 1 prior chemotherapy regimen.

Limitations of use: Use in combination with platinum-based chemotherapy is not recommended. Safety and efficacy of treatment for metastatic NSCLC with EGFR mutations other than exon 19 deletion or exon 21 (L858R) substitution have not been established.

Guideline recommendations:

Based on the American Society of Clinical Oncology (ASCO) and Ontario Health (Cancer Care Ontario) guidelines for therapy for stage IV NSCLC with driver mutations, erlotinib (either as monotherapy or in combination with either ramucirumab or bevacizumab) may be offered to patients with stage IV NSCLC and EGFR driver alterations if osimertinib is not available (ASCO/CCO [Hanna 2021]).

Pancreatic cancer, locally advanced, unresectable or metastatic: First-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer (in combination with gemcitabine).

Guideline recommendations:

According to ASCO guidelines for locally advanced, unresectable pancreatic cancer, if disease progression occurs following induction with an initial systemic combination therapy regimen, treatment according to guidelines for metastatic pancreatic cancer should be offered (in appropriate patients) (ASCO [Balaban 2016]).

The updated ASCO guidelines for metastatic pancreatic cancer recommend gemcitabine monotherapy as first-line therapy (when there is a preference for cancer-directed treatment) in patients with an ECOG performance status of 2 or a comorbidity profile that prohibits more aggressive therapy; erlotinib may be added to gemcitabine (with proactive dose/schedule adjustments to minimize toxicities) in this setting (ASCO [Sohal 2020]).

Use: Off-Label: Adult

Renal cell carcinoma, papillary (advanced)

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

Erlotinib may be confused with afatinib, crizotinib, dacomitinib, enasidenib, encorafenib, entrectinib, erdafitinib, eribulin, gefitinib, imatinib, lapatinib, lorlatinib, neratinib, nintedanib, osimertinib, regorafenib, SUNItinib, vandetanib.

Tarceva may be confused with Tresiba.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices includes among its list of drug classes which 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. Adverse reactions reported with monotherapy in adults.

>10%:

Cardiovascular: Chest pain (18%)

Dermatologic: Paronychia (14%), pruritus (13% to 16%), skin rash (60% to 85%; including acne vulgaris, bullous dermatitis [≤1%], dermal ulcer, desquamation, eczema, exfoliative dermatitis [≤1%], folliculitis, furuncle, hyperpigmentation, palmar-plantar erythrodysesthesia, skin fissure), xeroderma (12% to 21%)

Gastrointestinal: Anorexia (52%), decreased appetite (≥30%), diarrhea (20% to 62%; grades 3/4: ≤6%), mucosal swelling (18%), nausea (33%; grade 3: 3%), stomatitis (17%; grade 3: <1%), vomiting (≥20%)

Infection: Infection (24%)

Nervous system: Asthenia (≥30%), fatigue (52%)

Neuromuscular & skeletal: Arthralgia (13%), back pain (19%), musculoskeletal pain (11%)

Ophthalmic: Conjunctivitis (12% to 18%), eye disease (≤18%; including abnormal eyelash growth, decreased lacrimation, dry eye syndrome [12%], keratitis)

Respiratory: Cough (48%), dyspnea (41% to 45%)

1% to 10%: Hepatic: Abnormal hepatic function tests (including increased serum alanine aminotransferase [grades ≥2: 3% to 4%], increased serum aspartate aminotransferase, increased serum bilirubin [grades ≥2: 5%])

<1%:

Gastrointestinal: Gastrointestinal perforation

Hepatic: Hepatic failure

Nervous system: Cerebrovascular accident

Renal: Severe renal disease

Frequency not defined: Renal: Renal insufficiency

Postmarketing:

Cardiovascular: Cardiomyopathy (Nagashio 2021)

Dermatologic: Alopecia (Costa 2007)

Gastrointestinal: Acute peptic ulcer with hemorrhage (gastritis, peptic ulcer) (Kim 2010), gastrointestinal hemorrhage, hematemesis, hematochezia, melena

Hepatic: Hepatitis (acute) (Saif 2008), hepatorenal syndrome (Gunturu 2010), hepatotoxicity (Kunimasa 2012, Yamanaka 2017)

Ophthalmic: Corneal ulcer (Tamura 2020), ophthalmic inflammation, uveitis (including anterior uveitis [Ali 2011])

Renal: Interstitial nephritis (Cho 2020)

Respiratory: Interstitial pulmonary disease (Tsubata 2012), pneumonitis (Vahid 2007)

Miscellaneous: Radiation recall phenomenon (Graziani 2014)

Contraindications

There are no contraindications listed in the manufacturer’s US labeling.

Canadian labeling: Hypersensitivity to erlotinib or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular events: Cerebrovascular accidents, MI, and myocardial ischemia have been reported (some fatal).

• Dermatologic toxicity: Bullous, blistering, and/or exfoliating skin conditions, some suggestive of Stevens-Johnson or toxic epidermal necrolysis (TEN), have been reported (some fatal). An acne-like rash commonly appears on the face, back, and upper chest. Generalized or severe acneiform, erythematous or maculopapular rash may occur. Skin rash may correlate with treatment response (Kiyohara 2013; Wacker 2007).

• GI perforation: GI perforation (including fatalities) has been reported; risk for perforation is increased with concurrent anti-angiogenic agents, corticosteroids, NSAIDs, and/or taxane based-chemotherapy, and patients with history of peptic ulcers or diverticular disease.

• Hematologic effects: Microangiopathic hemolytic anemia (MAHA) with thrombocytopenia has been reported (rarely) with erlotinib in combination with gemcitabine.

• Hemorrhage: Elevated INR and bleeding events (including fatal hemorrhage) have been reported when erlotinib was administered concomitantly with warfarin.

• Hepatotoxicity: Hepatic failure and hepatorenal syndrome have been reported (some fatal), particularly in patients with baseline hepatic impairment (although have also been observed in patients with normal hepatic function).

• Ocular toxicity: Corneal perforation and ulceration have been reported; decreased tear production, abnormal eyelash growth, keratoconjunctivitis sicca, or keratitis have also been reported and are known risk factors for corneal ulceration/perforation.

• Pulmonary toxicity: Rare, sometimes fatal, interstitial lung disease (ILD) has occurred; symptoms include acute respiratory distress syndrome, interstitial pneumonia, obliterative bronchiolitis, pneumonitis (including radiation and hypersensitivity), pulmonary fibrosis, and pulmonary infiltrates. The onset of symptoms has been within 5 days to more than 9 months after treatment initiation (median: 39 days).

• Renal impairment: Acute renal failure (some fatal), renal insufficiency, and hepatorenal syndrome have been reported, either secondary to hepatic impairment at baseline or due to severe dehydration; use with caution in patients with or at risk for renal impairment.

Disease-related concerns:

• NSCLC: Some factors which correlate positively with response to EGFR-tyrosine kinase inhibitor (TKI) therapy in NSCLC include patients who have never smoked, EGFR mutation, and patients of Asian origin. EGFR mutations, specifically exon 19 deletions and exon 21 mutation (L858R), are associated with better response to erlotinib in patients with NSCLC (Riely 2006). Erlotinib treatment is not recommended in patients with NSCLC with K-ras mutations; they are not likely to benefit from erlotinib treatment (Eberhard 2005; Miller 2008). K-ras mutations correlated with poorer outcome with EGFR-TKI therapy in patients with NSCLC (Jackman 2009; Masarelli 2007; Shepherd 2005). The cobas EGFR mutation test has been approved to detect EGFR mutation for NSCLC treatment.

Special populations:

• Smokers: Erlotinib levels may be lower in patients who smoke; advise patients to stop smoking. Smokers treated with 300 mg/day exhibited steady-state erlotinib levels comparable to former- and never-smokers receiving 150 mg/day (Hughes 2009).

Other warnings/precautions:

• Appropriate use: Select patients for metastatic NSCLC treatment based on EGFR exon 19 deletions and exon 21 mutation (L858R) in tumor or plasma specimens; if these mutations are not detected in plasma specimen, tumor tissue (if available) may be tested.

• Lactose intolerance: Product may contain lactose; avoid use in patients with congenital lactase deficiency, glucose-galactose malabsorption, or glucose intolerance.

Metabolism/Transport Effects

Substrate of CYP1A2 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP3A4 (weak)

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.

Antacids: May decrease the serum concentration of Erlotinib. Management: Separate the administration of erlotinib and any antacid by several hours in order to minimize the risk of a significant interaction. Risk D: Consider therapy modification

Broccoli: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy

Cannabis: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy

Ciprofloxacin (Systemic): May increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of severe adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Risk D: Consider therapy modification

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

CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy

CYP1A2 Inducers (Moderate): May decrease the serum concentration of Erlotinib. Management: Avoid the concomitant use of erlotinib and moderate CYP1A2 inducers if possible. If concomitant use is unavoidable, increase the erlotinib dose by 50 mg increments at 2-week intervals to a maximum of 300 mg. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Erlotinib. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and strong CYP3A4 inducers whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Erlotinib. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of erlotinib-associated adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Risk D: Consider therapy modification

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

FluvoxaMINE: May increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of severe adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Risk D: Consider therapy modification

Fosphenytoin-Phenytoin: Erlotinib may increase the serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease the serum concentration of Erlotinib. Management: Avoid use of erlotinib with phenytoin when possible. If required, increase erlotinib dose by 50 mg increments at 2 week intervals, as tolerated, to a max of 450 mg/day. Also monitor for increased phenytoin concentrations and toxicities. Risk D: Consider therapy modification

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

Grapefruit Juice: May increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of erlotinib-associated adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Risk D: Consider therapy modification

Histamine H2 Receptor Antagonists: May decrease the serum concentration of Erlotinib. Management: Avoid H2-antagonists in patients receiving erlotinib when possible. If concomitant treatment cannot be avoided, erlotinib should be dosed once daily, 10 hours after and at least 2 hours before H2-antagonist dosing. Risk D: Consider therapy modification

Hormonal Contraceptives: CYP3A4 Inducers (Weak) may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Erlotinib. Risk X: Avoid combination

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

Rifabutin: May decrease the serum concentration of Erlotinib. Management: Avoid concomitant use of erlotinib with rifabutin when possible. If such a combination cannot be avoided, consider increasing the erlotinib dose by 50 mg increments at 2 week intervals as tolerated, to a maximum of 450 mg/day. Risk D: Consider therapy modification

Rifapentine: May decrease the serum concentration of Erlotinib. Management: Avoid concomitant use of erlotinib with rifapentine when possible. If such a combination cannot be avoided, consider increasing the erlotinib dose by 50 mg increments at 2 week intervals as tolerated, to a maximum of 450 mg/day. Risk D: Consider therapy modification

Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Risk C: Monitor therapy

Sirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: Monitor therapy

St John's Wort: May decrease the serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and St John's wort whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider therapy modification

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

Tobacco (Smoked): May decrease the serum concentration of Erlotinib. Management: Avoid cigarette smoking during treatment with erlotinib whenever possible. If combined, increase erlotinib dose by 50 mg increments at 2-week intervals to a maximum of 300 mg daily. Risk D: Consider therapy modification

Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider therapy modification

Warfarin: Erlotinib may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy

Food Interactions

Erlotinib bioavailability is increased with food. Grapefruit or grapefruit juice may decrease metabolism and increase erlotinib plasma concentrations. Management: Administer on an empty stomach at least 1 hour before or 2 hours after the ingestion of food. Avoid grapefruit and grapefruit juice. Maintain adequate nutrition and hydration, unless instructed to restrict fluid intake.

Reproductive Considerations

Females of reproductive potential should use effective contraception during treatment and for at least 1 month after the last erlotinib dose.

Pregnancy Considerations

Erlotinib crosses the placenta (Ji 2015; Jovelet 2015). Information related to the use of erlotinib in pregnancy is limited (Ji 2015; Rivas 2012; Zambelli 2008). Based on the mechanism of action and data from animal reproduction studies, erlotinib may cause fetal harm if administered in pregnancy.

Breastfeeding Considerations

It is not known if erlotinib is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant (including bullous and exfoliative skin disorders, diarrhea, hepatotoxicity, interstitial lung disease, microangiopathic hemolytic anemia with thrombocytopenia, and ocular disorders) lactating women should not breastfeed during treatment and for 2 weeks after the final erlotinib dose.

Dietary Considerations

Avoid grapefruit and grapefruit juice.

Monitoring Parameters

LFTs (transaminases, bilirubin, and alkaline phosphatase [periodic], monitor more frequently in patients with hepatic impairment, biliary obstruction, or worsening liver function); renal function tests (periodic) and serum electrolytes (in patients at risk for dehydration; periodic); prothrombin time and INR (in patients on concomitant warfarin therapy); EGFR mutation status in patients with NSCLC adenocarcinoma (Keedy 2011); the cobas EGFR mutation test has been approved to detect EGFR mutation for first-line NSCLC treatment. Assess smoking status.

Consider a baseline ophthalmologic exam and reassess for ocular toxicities at 4 to 8 weeks after treatment initiation (Renouf 2012).

Monitor hydration status (for dehydration); monitor for signs/symptoms of pulmonary toxicity, dermatologic toxicity, and ocular toxicity. Monitor adherence.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends 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

Erlotinib reversibly inhibits overall epidermal growth factor receptor (HER1/EGFR) - tyrosine kinase activity. Intracellular phosphorylation is inhibited which prevents further downstream signaling, resulting in cell death. Erlotinib has higher binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations than for the wild type receptor.

Pharmacokinetics

Absorption: Oral: ~60% on an empty stomach; food increases to ~100%

Distribution: 232 L

Protein binding: 93% to albumin and alpha1-acid glycoprotein

Metabolism: Hepatic, via CYP3A4 (major), CYP1A1 (minor), CYP1A2 (minor), and CYP1C (minor)

Bioavailability: ~100% when given with food; ~60% without food

Half-life elimination: 36.2 hours

Time to peak, plasma: 4 hours

Excretion: Primarily as metabolites: Feces (83%; 1% as unchanged drug); urine (8%; <1% as unchanged drug)

Pharmacokinetics: Additional Considerations

Cigarette smoking: Smoking reduces erlotinib AUC by 64% (compared to former/never smokers); smokers had a 24% higher rate of erlotinib clearance.

Pricing: US

Tablets (Erlotinib HCl Oral)

25 mg (per each): $54.07 - $103.38

100 mg (per each): $268.87 - $283.94

150 mg (per each): $298.97 - $321.15

Tablets (Tarceva Oral)

25 mg (per each): $108.82

100 mg (per each): $298.88

150 mg (per each): $338.06

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.

Brand Names: International
  • Alvoceva (TW);
  • Birlotib (LK);
  • Erlocip-E (LB);
  • Erlonib (TH);
  • Erlonix (BD, LK);
  • Erlotaz (LK);
  • Erloter (AR);
  • Etopul (VN);
  • Lungitinib (EG);
  • Orlicert (BD);
  • Tarcenib (BD);
  • Tarceva (AE, AR, AT, AU, BB, BE, BG, BH, BR, CH, CL, CN, CO, CR, CU, CY, CZ, DE, DK, DO, EC, EE, ES, FI, FR, GB, GR, GT, HK, HN, HR, HU, IE, IL, IS, IT, JO, JP, KR, KW, LB, LK, LT, LU, LV, MT, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PL, PT, PY, QA, RO, RU, SE, SG, SI, SK, SV, TR, TW, UA, UY, VE, VN, ZA);
  • Zulenit (CR, DO, GT, HN, NI, PA, SV)


For country abbreviations used in Lexicomp (show table)
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  7. Ciuleanu T, Stelmakh L, Cicenas S, et al, “Efficacy and Safety of Erlotinib Versus Chemotherapy in Second-Line Treatment of Patients With Advanced, Non-Small-Cell Lung Cancer With Poor Prognosis (TITAN): A Randomised Multicentre, Open-Label, Phase 3 Study,” Lancet Oncol, 2012, 13(3):300-8. [PubMed 22277837]
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