erlotinib

High Alert

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).

Contraind./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.

Adv. 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)

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.

Availability ⬆ ⬇

(Generic available)

Tablets: 25 mg; 100 mg; 150 mg

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.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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

Therapeutic effects:

Decreased spread of lung or pancreatic cancer with increased survival.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors

Pharmacokinetics ⬆ ⬇

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

Distribution: Unknown.

Protein Binding: 93%.

Metabolism/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)

ROUTE		ONSET		PEAK		DURATION
PO		unknown		4 hr		24 hr

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.

section name header

Indications ⬇