er-LO-ti-nib

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors

• 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).

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

• Decreased spread of lung or pancreatic cancer with increased survival.

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

Distribution: Unknown.

Protein Binding: 93% protein bound.

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

Half-life: 36 hr.

(plasma concentrations)

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)
• Women of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: MYOCARDIAL INFARCTION/ISCHEMIA (PANCREATIC CANCER PATIENTS).

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.

Drug-Drug:

• Strong CYP3A4 inhibitors, including atazanavir, clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, or voriconazole↑ levels and the risk of toxicity; consider alternative therapy or ↓ erlotinib dose.
• Strong CYP3A4 inducers, including rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, or phenobarbital, ↓ levels and may ↓ response; consider alternative therapy or ↑ erlotinib dose.
• CYP1A2 inhibitors, including ciprofloxacin, may ↑ levels and the risk of toxicity; consider ↓ erlotinib dose if used with CYP3A4 inhibitor.
• Smoking may ↓ levels and may ↓ response; avoid smoking during therapy or consider ↑ erlotinib dose if smoking continues.
• Moderate CYP1A2 inducers, including teriflunomide, rifampin, or phenytoin; avoid concurrent use or ↑ erlotinib dose.
• May ↓ midazolam levels.
• May ↑ risk of bleeding with warfarin.
• ↓levels with proton pump inhibitors, H₂ blockers, and antacids; 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 may ↓ response; alternative therapy or ↑ dose should be considered.

Drug-Food:

• Grapefruit juice or grapefruit, a strong CYP3A4 inhibitor, ↑ levels and the risk of toxicity; consider dose ↓

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 concomitant use, if possible); Concurrent use of strong CYP3A4 inducer: consider ↑ dose by 50 mg every 2 wk (max dose = 450 mg/day) (avoid concomitant 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 concomitant use, if possible); Concurrent use of strong CYP3A4 inducer: consider ↑ dose by 50 mg every 2 wk (max dose = 450 mg/day) (avoid concomitant 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.

(Generic available)

• Tablets: 25 mg; 100 mg; 150 mg;

• Assess respiratory status prior to and periodically during therapy. If dyspnea, cough, or fever occur, discontinue erlotinib, assess for interstitial lung disease, and institute treatment as needed.
• Assess for diarrhea. Usually responds to loperamide but may require dose reduction or discontinuation of therapy if unresponsive to therapy or patient becomes dehydrated.
• Assess skin during therapy. If bullous, blistering, and exfoliative skin conditions, including Stevens-Johnson syndrome/toxic epidermal necrolysis, occur, interrupt or discontinue treatment. Skin rash may require treatment with corticosteroids or anti-infectives with anti-inflammatory properties; acne treatments may aggravate dry skin and erythema.
• Assess eyes periodically during therapy. Discontinue erlotinib if corneal ulceration occurs. Hold erlotinib if Grade 3 or 4 keratitis, or Grade 2 lasting >2 wk, or if acute or worsening eye pain or disorders occur.
• Assess for GI pain. Patients receiving concomitant antiangiogenic agents, corticosteroids, NSAIDs, and/or taxane-based chemotherapy, or who have prior history of peptic ulceration or diverticular disease, are at increased risk for GI perforation. Permanently discontinue erlotinib in patients who develop gastrointestinal perforation.

• 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 for the detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.
  • Monitor liver function tests (AST, ALT, bilirubin, alkaline phosphatase) periodically during therapy. Consider dose reduction or discontinuation of therapy if severe changes in liver function (doubling or tripling of transaminase levels in patients with pre-existing hepatic impairment or total bilirubin 3 times upper limit of normal and/or transaminases 5 times upper limit of normal in patients without pre-existing hepatic impairment) occur.
  • Monitor renal function and electrolytes in patients at risk for dehydration. Withhold therapy if dehydration or Grade 3 or 4 renal toxicity occurs.
  • Monitor INR regularly in patients taking warfarin. May cause ↑ INR.

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

• Instruct patient to take erlotinib as directed.
• Advise patient to notify health care professional if severe or persistent diarrhea, nausea, anorexia, vomiting, onset or worsening of skin rash, unexplained dyspnea or cough, eye irritation, or signs and symptoms of a cerebrovascular accident (sudden weakness; paralysis [an inability to move] or numbness of the face, arms, or legs, especially on one side of the body; confusion; trouble speaking or understanding speech; trouble seeing in one or both eyes; problems breathing; dizziness, trouble walking, loss of balance or coordination, unexplained falls; loss of consciousness; sudden and severe headache) occur.
• Instruct patient to avoid proton pump inhibitors and if antacids are necessary, separate antacids and erlotinib dose by several hr. If therapy with H₂ antagonists is required, take erlotinib 10 hr after H₂ antagonist and at least 2 hr before next dose of H₂ antagonist.
• 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 decrease skin reactions.
• Instruct patient to discontinue smoking during therapy; smoking decreases blood levels of erlotinib.
• May cause fetal harm. Caution females of reproductive potential to use highly effective contraceptive during and for at least 1 mo after completion of therapy and to avoid breastfeeding during and for at least 2 wk following last dose. Advise female patients to notify health care professional if pregnancy is planned or suspected.

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

Tarceva