afatinib

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

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);
Asian ethnicity (↑ risk of interstitial lung disease [ILD]);
Severe renal impairment (↓ dose);
Severe hepatic impairment (dose adjustment may be necessary);
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, diarrhea, nausea, stomatitis, vomiting, weight loss, GI PERFORATION, HEPATOTOXICITY, PANCREATITIS

Resp: 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; continue until disease progression or unacceptable toxicity. Concurrent use of P-gp inhibitors: If combination not tolerated, ↓ dose by 10 mg/day. Concurrent use of P-gp inducers:↑ dose by 10 mg/day as tolerated.

Renal Impairment

PO (Adults ): eGFR 15–29 mL/min: 30 mg once daily; continue 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 >48 hr despite use of antidiarrheal agent (Grade ≥2), hold until diarrhea resolves to Grade ≤1: then resume with ↓ dose of 10 mg/day. Permanently discontinue afatinib for severe or intolerable adverse reactions occurring at 20 mg/day.
Monitor for development of severe cutaneous adverse reactions, including signs/symptoms of prodrome of fever, malaise, mucosal lesions, progressive skin rash, blisters, lymphadenopathy, conjunctivitis, myalgias, hepatitis, and/or eosinophilia. If Grade 2 cutaneous lesions last ≥7 days, are intolerable, or are Grade ≥3: Hold therapy until reaction resolves to Grade ≤1 and resume at 10 mg/day less than dosage at which the adverse event occurred. If life-threatening bullous, blistering, or exfoliating skin lesions occur: permanently discontinue afatinib.
Monitor for signs/symptoms of ILD (lung infiltration, pneumonitis, acute respiratory distress syndrome, allergic alveolitis); If ILD confirmed: Permanently discontinue afatinib.
Monitor for signs/symptoms of ileus (abdominal distention, constipation, decreased or absent bowel sounds) or GI perforation (nausea, abdominal pain, tarry stools, coffee ground emesis, pallor, anemia). If GI perforation occurs: Permanently discontinue afatinib.
Monitor for signs/symptoms of keratitis (acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, red eye) during therapy. If persistent ulcerative keratitis occurs: Permanently discontinue afatinib.
Monitor for signs/symptoms of hepatotoxicity such as fatigue, nausea, upper abdominal pain, jaundice, scleral icterus, dark urine, or clay-colored stools.

Lab Test Considerations:

Screen for the presence of EGFR exon 19 deletions or exon 21 (L858R) substitution mutations in tumor specimens with an FDA-approved companion diagnostic test.
Monitor liver function tests periodically during therapy. May cause ↑ AST and ALT. If severe decline in liver function occurs: Permanently discontinue afatinib. .
- May cause hypokalemia.

Implementation ⬆ ⬇

During administration and when preparing or handling tablets, wear double chemotherapy gloves, protective gown, and hair and shoe covers; optimally prepare in a ventilated control device. Respiratory (N95) protection and eye/face protection is needed if there is risk of patient vomiting or spitting up. Single chemotherapy gloves are appropriate if handling and administering intact tablets from a unit-dose package. Healthcare providers who are actively trying to conceive, who are pregnant or may become pregnant, and who are breastfeeding should avoid handling.
PO: Administer once daily on an empty stomach, ≥1 hr before or 2 hr after meals.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of afatinib. Instruct patient to take 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/symptoms of keratitis occur. 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 cause fetal harm. Advise women of reproductive potential to notify health care professional if pregnancy is planned, to use highly effective contraception, and to avoid breastfeeding during and for ≥2 wk after last dose. May impair fertility in men and women.

Evaluation/Desired Outcomes ⬆ ⬇

Decreased spread of NSCLC.

US Brand Names ⬆ ⬇

Canadian Brand Names ⬆ ⬇

Code ⬆

NDC Code

0597- Boehringer Ingelheim Pharmaceuticals, Inc.
- 0597-0137- Gilotrif
  - 0597-0137-30- 1 BOTTLE in 1 CARTON (0597-0137-30) / 30 TABLET, FILM COATED in 1 BOTTLE

0597- Boehringer Ingelheim Pharmaceuticals, Inc.
- 0597-0137- Gilotrif
  - 0597-0137-90- 1 BOTTLE in 1 CARTON (0597-0137-90) / 30 TABLET, FILM COATED in 1 BOTTLE

0597- Boehringer Ingelheim Pharmaceuticals, Inc.
- 0597-0138- Gilotrif
  - 0597-0138-30- 1 BOTTLE in 1 CARTON (0597-0138-30) / 30 TABLET, FILM COATED in 1 BOTTLE

0597- Boehringer Ingelheim Pharmaceuticals, Inc.
- 0597-0138- Gilotrif
  - 0597-0138-95- 1 BOTTLE in 1 CARTON (0597-0138-95) / 30 TABLET, FILM COATED in 1 BOTTLE

0597- Boehringer Ingelheim Pharmaceuticals, Inc.
- 0597-0141- Gilotrif
  - 0597-0141-30- 1 BOTTLE in 1 CARTON (0597-0141-30) / 30 TABLET, FILM COATED in 1 BOTTLE

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇