- First-line treatment of metastatic non-small cell lung cancer (NSCLC) where the tumor has non-resistant epidermal growth factor receptor (EGFR) mutations detectable by an FDA-approved test.
- Treatment of metastatic squamous NSCLC progressing after platinum chemotherapy.
Inhibits tyrosine kinases which results in slowed proliferation of specific tumor cell lines.
Decreased spread of NSCLC.
Absorption: Well absorbed (92%) following oral administration; absorption is decreased by high fat meal.
Metabolism and Excretion: Metabolites occur partly as protein-bound products. Excretion is primarily fecal (85%) as parent drug; 4% excreted in urine.
Half-life: 37 hr
TIME/ACTION PROFILE (improved progression-free survival)
|PO||3 mo||12 mo||20 mo|
- Tumors with resistant EGFR mutations;
- Lactation: Discontinue drug or discontinue breastfeeding;
- OB: May cause fetal harm.
Use Cautiously in:
- Severe renal impairment (↓ dose);
- Severe hepatic impairment (dose adjustment may be necessary);
- Asian ethnicity (may be ↑ susceptible to interstitial lung disease);
- Rep: Women of reproductive potential;
- Pedi: Safety and effectiveness not established.
Adverse Reactions/Side Effects
Derm: STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, cutaneous reactions (including bullous/blistering/exfoliating reactions, acneiform eruptions and palmar-plantar erythrodysesthesia), dry skin, paronychia, pruritus, rash
EENT: conjunctivitis, epistaxis, keratitis, rhinorrhea
GI: HEPATOTOXICITY, PANCREATITIS, diarrhea, ↓ appetite, ↓ weight, nausea, stomatitis, vomiting
F and E: hypokalemia
Resp: INTERSTITIAL LUNG DISEASE
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Concurrent use of P-gp inhibitors including amiodarone, cyclosporine, erythromycin, itraconazole, ketoconazole, quinidine ritonavir, saquinavir, tacrolimus, or verapamil ↑ blood levels and the risk of toxicity; dosage adjustment may be necessary (ritonavir may be given concurrently or 6 hr after).
- Concurrent use of P-gp inducers including carbamazepine, phenobarbital, phenytoin, or rifampin↓ blood levels and may ↓ effectiveness; dosage adjustment may be necessary.
PO (Adults) 40 mg once daily; concurrent use of P-gp inhibitors–↓ dose by 10 mg/day if necessary; concurrent use of P-gp inducers–↑ dose by 10 mg/day if necessary. Continue until disease progression or occurrence of unacceptable toxicity.
PO (Adults) eGFR 15–29 mL/min–30 mg once daily.
Tablets: 20 mg, 30 mg, 40 mg
- Monitor for diarrhea; occurs frequently. Provide patient with an antidiarrheal agent (loperamide) at the onset of diarrhea and until diarrhea ceases for 12 hrs. If diarrhea is severe and lasts more than 48 hr despite use of antidiarrheal agent (Grade 2 or higher), withhold afatinib until diarrhea resolves to Grade 1 or less, then resume with reduced dose of 10 mg/day.
- Assess for cutaneous reactions (bullous, blistering, exfoliative lesions; rash, erythema, acneiform rash) periodically during therapy. Discontinue afatinib if life-threatening lesions or prolonged Grade 2 cutaneous lesions lasting ≥7 days, intolerable Grade 2, or Grade 3 cutaneous reactions occur. Withhold afatinib until reaction resolves to Grade 1 or less and resume at 10 mg/day.
- Monitor for signs and symptoms of interstitial lung disease (lung infiltration, pneumonitis, acute respiratory distress syndrome, allergic alveolitis); may occur more commonly in patients of Asian ethnicity. Withhold afatinib if symptoms occur; discontinue if interstitial lung disease is confirmed.
Lab Test Considerations:
Monitor liver function tests periodically during therapy. If severe decline in liver function occurs, discontinue afatinib. May cause ↑ AST and ALT.
- May cause hypokalemia.
- Diarrhea (Side Effects)
- PO Administer once daily on an empty stomach, at least 1 hr before or 2 hrs after meals.
- Instruct patient to take afatinib as directed. Take missed dose as soon as remembered unless within 12 hrs of next dose, then omit and take next dose at scheduled time; do not double doses.
- Caution patient to notify health care professional if signs and symptoms of keratitis (acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, and/or red eye) occur. Withhold if symptoms occur; if ulcerative keratitis is confirmed, discontinue afatinib. Advise patient that use of contact lenses is also a risk factor.
- Advise patient to wear sunscreen and protective clothing during therapy to minimize risk of skin disorders.
- Inform patient that diarrhea occurs in most patients and may cause dehydration and renal impairment. Notify health care professional if diarrhea is severe or persistent, if new or worsening lung symptoms (difficulty breathing, shortness of breath, cough, fever), symptoms of liver problems (yellow skin or whites of eyes, dark brown urine, pain on right side of abdomen, unusual bleeding or bruising, lethargy) or if symptoms of left ventricular dysfunction (shortness of breath, exercise intolerance, cough, fatigue, swelling or ankles or feet, palpitations, sudden weight gain) occur.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Rep: Advise female patients to use highly effective contraception during and for at least 2 wks after last dose and to avoid breast feeding. If pregnancy occurs, instruct patient to notify health care professional immediately.
Decreased spread of non-small cell lung cancer.
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