erlotinib

erlotinib,

a miscellaneous antineoplastic.

indication This drug is used in the treatment of non-small cell lung cancer.

contraindications Pregnancy and known hypersensitivity to this drug prohibit its use.

adverse effects A life-threatening side effect of this drug is interstitial lung disease. Common side effects include nausea, diarrhea, vomiting, anorexia, mouth ulceration, rash, conjunctivitis, eye pain, fatigue, infection, cough, and dyspnea.

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erlotinib Warning - High-alert drug!

Tarceva

Pharmacologic class: Epidermal growth factor receptor (EGFR) inhibitor

Therapeutic class: Antineoplastic

Pregnancy risk category D

Action

Unclear. Drug inhibits intracellular phosphorylation of tyrosine kinase associated with EGFR, which is expressed on cell surface of both normal cells and cancer cells.

Availability

Tablets: 25 mg, 100 mg, 150 mg

⊘Indications and dosages

➣ Locally advanced or metastatic non-small-cell lung cancer after failure of at least one chemotherapy regimen

Adults: 150 mg P.O. at least 1 hour before or 2 hours after food ingestion, continued until disease progresses or unacceptable toxicity occurs

➣ First-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer (given with gemcitabine)

Adults: 100 mg P.O. daily at least 1 hour before or 2 hours after food ingestion, continued until disease progresses or unacceptable toxicity occurs

Dosage adjustment

• Severe diarrhea
• Pretreatment with CYP3A4 inducers
• Concurrent use of potent CYP3A4 inhibitors (such as ketoconazole)
• Acute onset of new or progressing pulmonary symptoms

Off-label uses

• Colorectal and renal cell cancer
• Malignant glioma

Contraindications

None

Precautions

Use cautiously in:
• hepatic impairment, diarrhea, pulmonary symptoms, suspected interstitial lung disease (such as pneumonitis, interstitial pneumonia, obliterative bronchiolitis, pulmonary fibrosis, adult respiratory distress syndrome, or lung filtration)
• concurrent warfarin therapy
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• Give at least 1 hour before or 2 hours after food ingestion.
• Know that concurrent administration with platinum-based chemotherapy has no clinical benefit and isn't recommended in patients with locally advanced or metastatic non-small-cell lung cancer.
• Reduce dosage in 50-mg decrements in patients with severe diarrhea who don't respond to loperamide or become dehydrated, those with severe skin reactions, and those receiving strong CYP3A4 inhibitors.
• Interrupt therapy if patient develops acute onset of new or progressing pulmonary symptoms pending diagnostic evaluation. If interstitial lung disease develops, discontinue drug and administer appropriate interventions.

Route	Onset	Peak	Duration
P.O.	Unknown	4 hr	Unknown

Adverse reactions

CNS: fatigue

EENT: conjunctivitis, keratoconjunctivitis sicca

GI: nausea, vomiting, diarrhea, abdominal pain, anorexia, stomatitis

Respiratory: dyspnea, cough, interstitial lung disease

Skin: rash, pruritus, dry skin

Other: infection

Interactions

Drug-drug. CYP3A4 inhibitors (such as clarithromycin, indinavir, itraconazole, ketoconazole, ritonavir, saquinavir, telithromycin): increased erlotinib blood level

CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, rifampin): decreased erlotinib blood level

Warfarin, other coumarin anticoagulants: elevated INR, increased bleeding risk

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, bilirubin: increased

Liver function tests: abnormal

Drug-food. Any food: increased erlotinib bioavailability

Drug-herb. Coenzyme Q10: decreased chemotherapy efficacy

St. John's wort: decreased erlotinib blood level

Patient monitoring

• Perform periodic liver function testing.
• Monitor INR and prothrombin time regularly in patients receiving warfarin, other coumarin anticoagulants, or nonsteroidal anti-inflammatory drugs.
• Monitor for signs and symptoms of respiratory disorders.

Patient teaching

☞ Advise patient to seek immediate medical attention for severe or persistent diarrhea, nausea, vomiting, anorexia, eye irritation, or onset or worsening of unexplained shortness of breath or cough.
• Caution female with childbearing potential to avoid pregnancy during therapy.
• Advise breastfeeding patient to stop breastfeeding during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.