Drug information of Afatinib

Afatinib

Drug group:

 Antineoplastic agent; a second-generation inhibitor of receptor tyrosine kinases. Afatinib is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Afatinib is used to treat a certain type of non-small cell lung cancer that has spread to other parts of the body. Afatinib is used for this condition only if your tumor has a specific genetic marker for which your doctor will test.

Afatinib is also used to treat squamous non-small cell lung cancer that has spread to other parts of the body after other cancer medicine has been tried without successful treatment.

Mechanism of effect

 Covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB smutation.

In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2.

Pharmacodynamic

Inhibits phosphorylation and in vitro proliferation of cell lines expressing wild-type EGFR and cell lines expressing del19 or L858R mutations, including some with the secondary T790M mutation. (which confers resistance to the first-generation tyrosine kinase inhibitors erlotinib and gefitinib)

Pharmacokinetics

  • Bioavailability: 92%
  • Peak plasma time: 2-5 hr
  • High fat meal decreases Cmax by 50% and AUC by 39% relative to the fasted condition (take on empty stomach)
  • Protein bound: 95%
  • Covalent adducts to proteins are the major circulating metabolites of afatinib and enzymatic metabolism of afatinib is minimal.
  • Afatinib is a P-gp substrate and an inhibitor; BCRP substrate and an inhibitor.
  • Half-life: 37 hr
  • Excretion: 85% (feces); 4% (urine)

Dosage

Metastatic Non-Small Cell Lung Cancer

Indicated for first-line treatment in metastatic non-small cell lung cancer (NSCLC) whose tumors have nonresistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test

40 mg PO q Day until disease progression or no longer tolerated by the patient.

Metastatic Squamous Non-Small Cell Lung Cancer

Indicated for metastatic squamous NSCLC progressing after platinum-based chemotherapy.

40 mg PO qDay until disease progression or no longer tolerated by the patient.

Alerts

May cause diarrhea that results in dehydration with or without renal impairment; some reported cases were fatal; withhold therapy for severe and prolonged diarrhea not responsive to antidiarrheal agents.

Postmarketing cases consistent with toxic epidermal necrolysis (TEN), including bullous and exfoliative skin disorders, and Stevens Johnson syndrome (SJS) reported; discontinue if life-threatening bullous, blistering, or exfoliating lesions occur; withhold therapy for severe and prolonged cutaneous reactions .

May increase risk for sunburn/phototoxicity; may worsen rash or acne; caution patients to limit sun exposure and where sunscreen and protective clothing. 

Interstitial lung disease (ILD) or ILD-like adverse reactions reported (eg, lung infiltration, pneumonitis, acute respiratory distress syndrome, alveolitis allergy) occurred in 1%, of these, 0.4% were fatal; discontinue therapy if ILD diagnosed.

Hepatotoxicity reported; monitor with periodic liver testing; withhold or discontinue therapy for severe or worsening liver tests.

Keratitis, characterized as acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, and/or red eye occurred in 0.8%; withhold or discontinue therapy for confirmed ulcerative keratitis.

Based on its mechanism of action, afatinib can cause fetal harm; advise pregnant women and females of reproductive potential of potential risk to fetus and to use effective contraception. 

Hepatic impairment: Use in severe hepatic impairment (Child-Pugh class C) has not been studied; closely monitor patients with severe impairment, may require dosage adjustments if not tolerated. 

Renal impairment: Dosage reduction is recommended in patients with severe renal impairment (estimated glomerular filtration rate 15 to 29 mL/minute/1.73 m2).

Points of recommendation

To make sure this medicine is safe for you, tell your doctor if you have:

  • If you have an allergy to this medicine or any other part of it.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

Have blood work checked as you have been told by the doctor. Talk with the doctor.

If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.

If you get diarrhea, you will need to make sure to avoid getting dehydrated. Drink plenty of fluids and watch for weight loss. Talk with your doctor.

You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.

Very bad and sometimes deadly skin rashes have happened with afatinib. Talk to your doctor about any skin changes you may have.

This medicine may affect fertility. Fertility problems may lead to not being able to get pregnant or father a child. Talk with the doctor.

This medicine may cause harm to the unborn baby if you take it while you are pregnant.

Use birth control that you can trust to prevent pregnancy while taking this medicine and for at least 2 weeks after stopping the drug.

If you get pregnant while taking afatinib or within 2 weeks after your last dose, call your doctor right away.

Take this medication by mouth as directed by your doctor, usually once daily at least 1 hour before or 2 hours after a meal.

Take on an empty stomach. Take 1 hour before or 2 hours after meals. Avoid wearing contacts unless told to wear them by your doctor.

To gain the most benefit, do not miss doses.

Take a missed dose as soon as you think about it. If it is less than 12 hours until the next dose, skip the missed dose and go back to your normal time. Do not take 2 doses at the same time or extra doses.

Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.

Pregnancy level

D


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