afatinib

afatinib

(a-fa-ti-nib ) ,

Gilotrif

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: kinase inhibitors
Pregnancy Category: D

Indications

First-line treatment of metastatic non-small cell lung cancer (NSCLC) where the tumor has a specific epidermal growth factor receptor (EGFR) deletion or substitution mutation detectable by an FDA-approved test.

Action

Inhibits tyrosine kinases which results in slowed proliferation of specific tumor cell lines

Therapeutic effects

Decreased spread of NSCLC

Pharmacokinetics

Absorption: Well abosrbed (92%) following oral administration; absorption is decreased by high fat meal.
Distribution: Unknown
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)

ROUTEONSETPEAKDURATION
PO3 mos12 mos20 mos

Contraindications/Precautions

Contraindicated in: Lactation: Discontinue drug or discontinue breast feeding; Obstetric: May cause fetal harm.
Use Cautiously in: Moderate-severe renal or hepatic impairment (dose adjustment may be necessary);genetic implication Asian ethnicity (may be ↑ susceptible to interstitial lung disease); Obstetric: Patients with child-bearing potential (highly effective contraception should be used during and for at least 2 wks after last dose); Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Ear, Eye, Nose, Throat

  • keratitis

Respiratory

  • interstitial lung disease (life-threatening)

Gastrointestinal

  • hepatic toxicity (life-threatening)
  • diarrhea (most frequent)
  • ↓ appetite
  • stomatitis

Dermatologic

  • cutaneous reactions (including bullous/blistering/exfoliating reactions, acneiform erruptions and palmar-plantar erythrodysesthesia)
  • dry skin
  • pruritus
  • paronychia
  • rash

Fluid and Electrolyte

  • hypokalemia

Interactions

Drug-Drug interaction

Concurrent use of P-gp inhibitors including amiodarone, cyclosporine, erythromycin, itraconazole, ketoconazole, quinidineritonavir, 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, phenytoinrifampicin or rifampin ↓ blood levels and may ↓ effectiveness; dosage adjustment may be necessary.

Route/Dosage

Oral (Adults) 40 mg/day; concurrent use of P-gp inhibitors—reduce dose by 10 mg/day if necessary; concurrent use of P-gp inducers—increase dose by 10 mg/day if necessary. Dose reductions recommended for various toxicities. Continue until disease progression or occurrence of unacceptable toxicity

Availability

Tablets: 20 mg, 30 mg, 40 mg

Nursing implications

Nursing assessment

  • 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; genetic implication 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.

Potential Nursing Diagnoses

Diarrhea (Side Effects)

Implementation

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

Patient/Family Teaching

  • 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.
  • 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.

Evaluation/Desired Outcomes

  • Decreased spread of non-small cell lung cancer.
References in periodicals archive ?
Several rationally designed, targeted covalent inhibitors have recently advanced in clinical development (neratinib, afatinib, PCI-32765 and the Avlia clinical candidate, AVL-292).
Contract award: competition for the award of contracts for the provision of health care - hospital treatment - the drug program - treatment of small cell lung cancer with the use of afatinib.
Contract notice: Delivery of the medicinal product - chemotherapy custom chemical name afatinib, the character - a tablet with the trade name .
Patients who received first-line afatinib compared to standard chemotherapy lived more than one year longer, achieving a 41% reduction in the risk of death
Afatinib is the first and only EGFR targeting agent to demonstrate an overall survival benefit compared to chemotherapy in the first-line treatment of NSCLC patients with EGFR mutations.
Boehringer Ingelheim today announced data from a pre-specified subgroup-analysis of the pivotal Phase III LUX-Lung 3 trial which demonstrated that Asian non-small cell lung cancer (NSCLC) patients with the most common type of EGFR mutation, (exon 19 deletion; del19), lived significantly longer after receiving first-line treatment with afatinib compared to chemotherapy (33.
LUX-Lung 8 trial met its primary endpoint of improving progression-free survival in patients treated with afatinib versus erlotinib after failure of first-line, platinum-based chemotherapy, reducing the risk of disease progression by 18%
Crizotinib, erlotinib and afatinib are approved for first-line treatment of ALK-positive and EGFR-mutant advanced NSCLC, respectively, and have proven to be superior to standard cytotoxic chemotherapy in these molecular subsets of patients.
Boehringer will launch clinical investigation of the vaccine, called CV9202, in at least two different lung cancer settings, along with afatinib in patients with advanced or metastatic epidermal growth factor receptor (EGFR) mutated non small cell lung cancer (NSCLC) and with chemo-radiation therapy in patients with unresectable stage III NSCLC.
Boehringer Ingelheim will start clinical investigation of CV9202 in at least two different lung cancer settings, in combination with afatinib in patients with advanced or metastatic epidermal growth factor (EGFR) mutated non-small cell lung cancer (NSCLC) and in combination with chemo-radiation therapy in patients with unresectable stage III NSCLC.
Clinical investigation of CV9202 will be initiated in at least two different lung cancer treatment settings, in combination with Boehringer Ingelheim's afatinib, and in the chemo-radiation therapy setting