General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Genetic Implications:

Pronunciation:
er-lo-ti-nib

Trade Name(s)

• Tarceva

Ther. Class.

antineoplastics

Pharm. Class.

enzyme inhibitors

Indications

•  Treatment of metastatic non-small cell lung cancer (NSCLC) that has epidermal growth factor exon 19 deletions or exon 21 substitution mutations in patients who are receiving first-line, maintenance, or second- or greater line treatment after progression following ≥1 previous chemotherapy regimen.
• First-line therapy for locally advanced, surgically unresectable, or metastatic pancreatic cancer (in combination with gemcitabine).

Action

 Inhibits the enzyme tyrosine kinase, which is associated with human epidermal growth factor receptor (EGFR); blocks growth stimulation signals in cancer cells.

Therapeutic Effect(s):

Decreased spread of lung or pancreatic cancer with increased survival.

Pharmacokinetics

Absorption: 60% absorbed; bioavailability ↑ to 100% with food.

Distribution: Unknown.

Protein Binding: 93%.

Metabolism and Excretion: Mostly metabolized by the liver, primarily by the CYP3A4 isoenzyme. 83% excreted in feces (<1% as unchanged drug); 8% excreted in urine (<1% as unchanged drug).

Half-life: 36 hr.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• OB:  Pregnancy;
• Lactation: Lactation.

Use Cautiously in:

• Hepatic impairment;
• Previous chemotherapy/radiation, pre-existing lung disease, metastatic lung disease (may ↑ risk of interstitial lung disease);
• Rep:  Women of reproductive potential;
• Pedi:  Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: MYOCARDIAL INFARCTION/ISCHEMIA (patients with pancreatic cancer)

Derm: rash, BULLOUS AND EXFOLIATIVE SKIN DISORDERS, dry skin, pruritus

EENT: ↓ tear production, abnormal eyelash growth, conjunctivitis, corneal perforation, corneal ulceration, keratitis

GI: diarrhea, HEPATOTOXICITY, ↑ liver enzymes, abdominal pain, anorexia, GI PERFORATION, nausea, stomatitis, vomiting

GU: RENAL FAILURE

Hemat: microangiopathic hemolytic anemia with thrombocytopenia (pancreatic cancer patients)

Neuro: CEREBROVASCULAR ACCIDENT (pancreatic cancer patients), fatigue

Resp: dyspnea, cough, INTERSTITIAL LUNG DISEASE (ILD)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Strong CYP3A4 inhibitors, including  atazanavir,  clarithromycin,  itraconazole,  ketoconazole,  nefazodone,  nelfinavir,  ritonavir, or  voriconazole, may ↑ levels and risk of toxicity; consider alternative therapy or ↓ erlotinib dose.
•  Strong CYP3A4 inducers, including  rifampin,  rifabutin,  rifapentine,  phenytoin,  carbamazepine, or  phenobarbital, may ↓ levels and effectiveness; consider alternative therapy or ↑ erlotinib dose.
•  CYP1A2 inhibitors, including  ciprofloxacin, may ↑ levels and risk of toxicity; consider ↓ erlotinib dose if used with CYP3A4 inhibitor.
•  Smoking  may ↓ levels and effectiveness; avoid smoking during therapy or consider ↑ erlotinib dose if smoking continues.
•  Moderate CYP1A2 inducers, including  teriflunomide,  rifampin, or  phenytoin, may ↓ levels and effectiveness; avoid concurrent use or ↑ erlotinib dose.
• May ↓  midazolam  levels.
• May ↑ risk of bleeding with  warfarin.
•  Proton pump inhibitors,  H₂  blockers, and  antacids  may ↓ levels and effectiveness; avoid concurrent use with  proton pump inhibitors ; take 10 hr after  H₂  antagonist  and ≥2 hr before next dose of  H₂  antagonist ; separate from  antacid  by several hr.

Drug-Natural Products:

 St. John's wort  may ↓ levels and effectiveness; consider alternative therapy or ↑ erlotinib dose.

Drug-Food:

Grapefruit juice or grapefruit may ↑ levels and risk of toxicity; consider ↓ erlotinib dose.

Route/Dosage

Non-Small Cell Lung Cancer

PO (Adults): 150 mg once daily;  Concurrent use of strong CYP3A4 inhibitor or concurrent use of CYP3A4 and CYP1A2 inhibitor (e.g., ciprofloxacin):  Consider ↓ dose in 50-mg increments (avoid concurrent use if possible);  Concurrent use of strong CYP3A4 inducer:  Consider ↑ dose by 50 mg every 2 wk (max dose = 450 mg/day) (avoid concurrent use if possible);  Concurrent cigarette smoking or concurrent use of moderate CYP1A2 inducer:  ↑ dose by 50 mg every 2 wk (max dose = 300 mg/day); immediately ↓ dose to recommended initial dose for indication upon smoking cessation.

Pancreatic Cancer

PO (Adults): 100 mg once daily.  Concurrent use of strong CYP3A4 inhibitor or concurrent use of CYP3A4 and CYP1A2 inhibitor (e.g., ciprofloxacin):  Consider ↓ dose in 50-mg increments (avoid concurrent use if possible);  Concurrent use of strong CYP3A4 inducer:  Consider ↑ dose by 50 mg every 2 wk (max dose = 450 mg/day) (avoid concurrent use if possible);  Concurrent cigarette smoking or concurrent use of moderate CYP1A2 inducer:  ↑ dose by 50 mg every 2 wk (max dose = 300 mg/day); immediately ↓ dose to recommended initial dose for indication upon smoking cessation.

Availability (generic available)

Tablets: 25 mg, 100 mg, 150 mg

Assessment

• Assess respiratory status before and periodically during therapy.  If dyspnea, cough, or fever occur,  hold and evaluate until resolved to Grade ≤1; resume therapy with ↓ dose by 50 mg.  If ILD confirmed,  discontinue erlotinib.
• Assess for GI pain and diarrhea.  If diarrhea unresponsive to loperamide or dehydration occurs,  hold erlotinib.  If GI perforation occurs,  discontinue erlotinib.
• Assess skin during therapy.  If severe rash unresponsive to medical management occurs,  hold until resolved to Grade ≤1; resume therapy with ↓ dose by 50 mg.  If bullous and exfoliative skin disorders occur,  discontinue erlotinib.
• Assess for ocular changes periodically during therapy.  If Grade 3 or 4 keratitis (or Grade 2 keratitis lasting >2 wk), or acute or worsening eye pain or disorders occurs,  hold erlotinib until resolved to Grade ≤1; resume therapy with ↓ dose by 50 mg.  If corneal perforation or ulcers occur,  discontinue erlotinib.

Lab Test Considerations:

  Test patients for EGFR exon 19 deletions or exon 21 (L858R) substitution mutations in plasma or tumor specimens prior to starting therapy; presence is required for therapy. Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics.

• Monitor AST, ALT, bilirubin, and alkaline phosphatase periodically during therapy. If tripling of transaminase levels in  patients with pre-existing hepatic impairment  or total bilirubin ≥3 times upper limit of normal (ULN) and/or transaminases ≥5 times ULN in  patients without pre-existing hepatic impairment , consider dose ↓ by 50 mg.
• Monitor renal function and serum electrolytes periodically during therapy.  If Grade 3 or 4 renal toxicity occurs,  hold erlotinib and evaluate until resolved to Grade ≤1; resume therapy with ↓ dose by 50 mg or discontinue erlotinib.
• Monitor INR regularly in patients taking warfarin.

Implementation

• Do not confuse Tarceva with Tresiba.
• PO Administer at ≥1 hr before or 2 hr after food.

Patient/Family Teaching

• Explain purpose and side effects of medication. Advise patient to read  Patient Information  before starting therapy.
• Advise patient to notify health care professional if severe or persistent diarrhea, nausea, anorexia, vomiting, rash, unexplained dyspnea or cough, eye irritation, or signs and symptoms of a cerebrovascular accident (sudden weakness, paralysis or numbness of face or extremities, confusion, trouble speaking or understanding, visual changes, problems breathing, dizziness, loss of balance or coordination, unexplained falls, loss of consciousness, sudden and severe headache) occur.
• Instruct patient to avoid proton pump inhibitors. If antacids are necessary, separate antacids and erlotinib by several hr. If therapy with H₂  antagonists is required, take erlotinib 10 hr after H₂  antagonist and ≥2 hr before next H₂  antagonist dose.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patient to wear sunscreen and protective clothing to ↓ skin reactions.
• Instruct patient to discontinue smoking during therapy.
• Rep:  May cause fetal harm. Caution women of reproductive potential to use highly effective contraceptive during therapy and for ≥1 mo after last dose and to avoid breastfeeding during and for ≥2 wk following last dose. Advise women to notify health care professional if pregnancy is planned or suspected.

Evaluation/Desired Outcomes

Decrease in spread of non-small cell lung or pancreatic cancer with increased survival.