erlotinib

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; maintenance treatment in patients whose disease hasn't progressed after four cycles of platinumbased first-line chemotherapy

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)

• concomitant use of anti-angiogenic agents, corticosteroids, nonsteroidal anti-inflammatory drugs, or taxane-based chemotherapy; prior history of peptic ulceration or diverticular disease

• 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.

See 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.

See Be aware that some cases of hepatorenal syndrome, acute renal failure, and renal insufficiency may be secondary to baseline hepatic impairment while others may be associated with severe dehydration. Interrupt therapy and take appropriate measures to intensively rehydrate patient, as needed.

See Discontinue drug if total bilirubin level is above three times upper limit of normal (ULN) or transaminase levels are above five times ULN versus pretreatment values; signs and symptoms of GI perforation occur; severe bullous, blistering, or exfoliating conditions develop; or acute or worsening ocular disorders such as eye pain occur.

Adverse reactions

CNS: fatigue

EENT: conjunctivitis, keratoconjunctivitis sicca corneal perforation and ulceration

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

GU: renal insufficiency, acute renal failure

Hepatic: hepatorenal syndrome, hepatic failure

Respiratory: dyspnea, cough, interstitial lung disease

Skin: rash, pruritus, dry skin, Stevens-Johnson syndrome, toxic epidermal necrolysis-like reactions

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

International Normalized Ratio: 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

Drug-behaviors. Smoking: decreased erlotinib plasma concentration

Patient monitoring

See Perform periodic serum electrolyte measurements and renal and liver function testing.

• Advise patient not to smoke while taking drug.

• Monitor INR and prothrombin time regularly in patients receiving warfarin, other coumarin anticoagulants, or nonsteroidal anti-inflammatory drugs.

See Monitor for signs and symptoms of respiratory disorders and GI perforation.

Patient teaching

See Advise patient to seek immediate medical attention for severe or persistent diarrhea, nausea, vomiting, anorexia, severe rash, eye pain, eye irritation, or onset or worsening of unexplained shortness of breath or cough.

• Advise patient not to smoke while taking drug.

• 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.