afatinib

Absorption: Well absorbed (92%) following oral administration; absorption is ↓ by high-fat meal.

Distribution: Unknown

Metabolism/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)

ROUTE	ONSET	PEAK	DURATION
PO	3 mo	12 mo	20 mo

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Tumors with resistant EGFR mutations;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Concurrent use of corticosteroids, NSAIDs, or antiangiogenic drugs, history of GI ulceration, history of diverticular disease, or history of bowel metastases (↑ risk of GI perforation);
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 in children;
Geri: risk of GI perforation in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: cutaneous reactions (including bullous/blistering/exfoliating reactions, acneiform eruptions and palmar-plantar erythrodysesthesia)dry skin, paronychia, pruritus, rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

EENT: conjunctivitis, epistaxis, keratitis, rhinorrhea

F and E: hypokalemia

GI: ↓appetite, ↓weight, diarrhea, nausea, stomatitis, vomiting, GI PERFORATION, HEPATOTOXICITY, PANCREATITIS

Resp: INTERSTITIAL LUNG DISEASE (ILD)

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

P-glycoprotein (P-gp) inhibitors, including amiodarone, cyclosporine, erythromycin, itraconazole, ketoconazole, quinidineritonavir, tacrolimus, or verapamil, may ↑ levels and risk of toxicity; dosage adjustment may be necessary (ritonavir may be given concurrently or 6 hr after).
P-gp inducers, including carbamazepine, phenobarbital, phenytoin, or rifampin may ↓ levels and effectiveness; dosage adjustment may be necessary.

Route/Dosage ⬆ ⬇

PO (Adults ): 40 mg once daily until disease progression or unacceptable toxicity. 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.

Renal Impairment

PO (Adults ): eGFR 15–29 mL/min: 30 mg once daily until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Tablets: 20 mg; 30 mg; 40 mg

Assessment ⬆ ⬇

Monitor for diarrhea; occurs frequently. Provide patient with an antidiarrheal agent (loperamide) at the onset of diarrhea and until diarrhea ceases for 12 hr. 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 ILD (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 ILD is confirmed.
Monitor for signs and symptoms of GI perforation (severe abdominal pain) during therapy. Permanently discontinue afatinib if perforation occurs.
Monitor for signs and symptoms of keratitis (acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, red eye) during therapy. May require interruption or discontinuation of afatinib.

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.

Implementation ⬆ ⬇

PO: Administer once daily on an empty stomach, at least 1 hr before or 2 hr after meals.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take afatinib as directed. Take missed dose as soon as remembered unless within 12 hr of next dose, then omit and take next dose at scheduled time; do not double doses. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
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), severe abdominal pain, 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: May be teratogenic. Advise females of reproductive potential to use highly effective contraception and to avoid breastfeeding during and for at least 2 wk after last dose. If pregnancy occurs, instruct patient to notify health care professional immediately. May impair fertility in males and females.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇