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Drug overview for GILOTRIF (afatinib dimaleate):
Generic name: AFATINIB DIMALEATE (a-FA-ti-nib)
Drug class: Antineoplastic - Protein-Tyrosine Kinase Inhibitors
Therapeutic class: Antineoplastics
Afatinib dimaleate, a second-generation inhibitor of receptor tyrosine kinases, is an antineoplastic agent.
No enhanced Uses information available for this drug.
Generic name: AFATINIB DIMALEATE (a-FA-ti-nib)
Drug class: Antineoplastic - Protein-Tyrosine Kinase Inhibitors
Therapeutic class: Antineoplastics
Afatinib dimaleate, a second-generation inhibitor of receptor tyrosine kinases, is an antineoplastic agent.
No enhanced Uses information available for this drug.
DRUG IMAGES
GILOTRIF 20 MG TABLET
GILOTRIF 30 MG TABLET
GILOTRIF 40 MG TABLET
The following indications for GILOTRIF (afatinib dimaleate) have been approved by the FDA:
Indications:
Epidermal growth factor receptor positive non-small cell lung cancer
Squamous cell carcinoma of lung
Professional Synonyms:
EGFR positive NSCLC
Epidermoid carcinoma of lung
SCC of lung
Squamous cell lung carcinoma
Squamous non-small cell lung cancer
Squamous NSCLC
Indications:
Epidermal growth factor receptor positive non-small cell lung cancer
Squamous cell carcinoma of lung
Professional Synonyms:
EGFR positive NSCLC
Epidermoid carcinoma of lung
SCC of lung
Squamous cell lung carcinoma
Squamous non-small cell lung cancer
Squamous NSCLC
The following dosing information is available for GILOTRIF (afatinib dimaleate):
Dosage of afatinib dimaleate is expressed in terms of afatinib.
If adverse effects occur during afatinib therapy, temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug may be necessary.
Permanently discontinue afatinib in patients who develop life-threatening bullous, blistering, or exfoliative skin lesions; interstitial lung disease; severe drug-induced hepatic impairment; GI perforation; persistent ulcerative keratitis; or symptomatic left ventricular dysfunction. The drug also should be permanently discontinued in patients who experience severe or intolerable adverse reactions to an afatinib dosage of 20 mg daily.
If adverse effects occur during afatinib therapy, temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug may be necessary.
Permanently discontinue afatinib in patients who develop life-threatening bullous, blistering, or exfoliative skin lesions; interstitial lung disease; severe drug-induced hepatic impairment; GI perforation; persistent ulcerative keratitis; or symptomatic left ventricular dysfunction. The drug also should be permanently discontinued in patients who experience severe or intolerable adverse reactions to an afatinib dosage of 20 mg daily.
Administer orally once daily. Administer on an empty stomach, at least 1 hour before or 2 hours after a meal. If a dose of afatinib is missed, the prescribed dose should be taken as soon as possible unless the next dose is within 12 hours; an additional dose should not be administered to replace the missed dose.
Store at 25oC (excursions permitted between 15-30oC). Store in original container and protect from excessive humidity and light.
Store at 25oC (excursions permitted between 15-30oC). Store in original container and protect from excessive humidity and light.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| GILOTRIF 30 MG TABLET | Maintenance | Adults take 1 tablet (30 mg) by oral route once daily at least 1 hour before or 2 hours after meals |
| GILOTRIF 40 MG TABLET | Maintenance | Adults take 1 tablet (40 mg) by oral route once daily at least 1 hour before or 2 hours after meals |
| GILOTRIF 20 MG TABLET | Maintenance | Adults take 2 tablets (40 mg) by oral route once daily at least 1 hour before or 2 hours after meals |
No generic dosing information available.
The following drug interaction information is available for GILOTRIF (afatinib dimaleate):
There are 0 contraindications.
There are 3 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Selected P-glycoprotein (P-gp) Substrates/Capmatinib SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Capmatinib is an inhibitor of the P-glycoprotein (P-gp) system. P-gp substrates with a narrow therapeutic index may be increased.(1) CLINICAL EFFECTS: Concurrent use of capmatinib with narrow therapeutic index P-gp substrates may result in elevated levels of the substrate, increasing the risk for adverse effects.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of capmatinib states that the concurrent use of narrow therapeutic index P-gp substrates should be avoided. If concurrent therapy cannot be avoided, the dosage of the narrow therapeutic index P-gp substrate should be decreased according to the substrate prescribing information.(1) DISCUSSION: In a study, capmatinib increased digoxin's area-under-curve (AUC) by 47% and maximum concentration (Cmax) by 74%.(1) Selected narrow therapeutic index P-gp substrates include: afatinib, betrixaban, digoxin, etoposide, everolimus, loperamide, sirolimus, and ubrogepant.(1,2) |
TABRECTA |
| Selected P-glycoprotein (P-gp) Substrates/Sotorasib SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sotorasib is an inhibitor of the P-glycoprotein (P-gp) system. P-gp substrates with a narrow therapeutic index may be increased.(1) CLINICAL EFFECTS: Concurrent use of sotorasib with narrow therapeutic index P-gp substrates may result in elevated levels of the substrate, increasing the risk for adverse effects.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sotorasib states that the concurrent use of narrow therapeutic index P-gp substrates should be avoided. If concurrent therapy cannot be avoided, the dosage of the narrow therapeutic index P-gp substrate should be decreased according to the substrate prescribing information.(1) DISCUSSION: In a study, sotorasib increased digoxin's area-under-curve (AUC) by 21% and maximum concentration (Cmax) by 91%.(1) Selected narrow therapeutic index P-gp substrates include: afatinib, betrixaban, digoxin, edoxaban, etoposide, and loperamide.(1,2) |
LUMAKRAS |
| Selected P-glycoprotein (P-gp) Substrates/Selpercatinib SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Selpercatinib is an inhibitor of the P-glycoprotein (P-gp) transporter and may increase the plasma concentrations of P-gp substrates.(1) CLINICAL EFFECTS: Concurrent use of selpercatinib with P-gp substrates may result in elevated levels of the substrate, increasing the risk for adverse effects.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of selpercatinib states that the concurrent use of narrow therapeutic index P-gp substrates should be avoided. If concurrent therapy cannot be avoided, follow recommendations for the narrow therapeutic index P-gp substrate according to the substrate's prescribing information.(1) DISCUSSION: In a study, selpercatinib increased dabigatran's area-under-curve (AUC) by 38% and maximum concentration (Cmax) by 43%.(1) Selected narrow therapeutic index P-gp substrates include: afatinib, betrixaban, bilastine, dabigatran, digoxin, edoxaban, etoposide, everolimus, loperamide, rimegepant, rivaroxaban, sirolimus, and ubrogepant.(1,2) |
RETEVMO |
There are 2 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Afatinib/P-glycoprotein (P-gp) Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibitors of P-glycoprotein (P-gp) may increase the absorption of afatinib.(1) CLINICAL EFFECTS: The concurrent administration of afatinib with an inhibitor of P-glycoprotein may result in elevated levels of afatinib and signs of toxicity. These signs may include but are not limited to worsening diarrhea, stomatitis, skin rash/exfoliation/bullae or paronychia.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of afatinib states the afatinib dose should be reduced by 10 mg if the addition of a P-glycoprotein inhibitor is not tolerated.(1) If afatinib dose was reduced due to addition of a P-gp inhibitor, resume the previous dose after the P-gp inhibitor is discontinued.(1) The manufacturer of vimseltinib states concurrent use with P-gp substrates should be avoided. If concurrent use cannot be avoided, take vimseltinib at least 4 hours prior to afatinib.(2) DISCUSSION: A drug interaction study evaluated the effects of ritonavir 200 mg twice daily on afatinib exposure. Administration of ritonavir 1 hour before afatinib administration increased systemic exposure by 48%. Afatinib exposure was not changed when ritonavir was administered simultaneously with or 6 hours after afatinib dose.(1) P-glycoprotein inhibitors linked to this monograph are: amiodarone, asunaprevir, azithromycin, belumosudil, carvedilol, cimetidine, clarithromycin, cobicistat, cyclosporine, danicopan, daridorexant, diosmin, dronedarone, erythromycin, flibanserin, fostamatinib, ginseng, glecaprevir/pibrentasvir, hydroquinidine, isavuconazonium, itraconazole, ivacaftor, josamycin, ketoconazole, lapatinib, ledipasvir, lonafarnib, mavorixafor, neratinib, osimertinib, propafenone, quinidine, ranolazine, ritonavir, saquinavir, sofosbuvir/velpatasvir/voxilaprevir, telaprevir, tepotinib, tezacaftor, tucatinib, valbenazine, vemurafenib, verapamil, vimseltinib and voclosporin.(1-3) |
ADDYI, ALYFTREK, AMIODARONE HCL, AMIODARONE HCL-D5W, ASPRUZYO SPRINKLE, AZITHROMYCIN, CARVEDILOL, CARVEDILOL ER, CIMETIDINE, CLARITHROMYCIN, CLARITHROMYCIN ER, COREG, COREG CR, CRESEMBA, CYCLOSPORINE, CYCLOSPORINE MODIFIED, E.E.S. 200, E.E.S. 400, ERY-TAB, ERYPED 200, ERYPED 400, ERYTHROCIN LACTOBIONATE, ERYTHROCIN STEARATE, ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE, EVOTAZ, FLIBANSERIN, GENGRAF, GENVOYA, HARVONI, INGREZZA, INGREZZA INITIATION PK(TARDIV), INGREZZA SPRINKLE, ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KALETRA, KALYDECO, KETOCONAZOLE, LANSOPRAZOL-AMOXICIL-CLARITHRO, LAPATINIB, LEDIPASVIR-SOFOSBUVIR, LOPINAVIR-RITONAVIR, LUPKYNIS, MAVYRET, MULTAQ, NEORAL, NERLYNX, NEXTERONE, NORVIR, NUEDEXTA, OMECLAMOX-PAK, PACERONE, PAXLOVID, PREZCOBIX, PROPAFENONE HCL, PROPAFENONE HCL ER, QUINIDINE GLUCONATE, QUINIDINE SULFATE, QUVIVIQ, RANOLAZINE ER, REZUROCK, RITONAVIR, ROMVIMZA, SANDIMMUNE, SPORANOX, STRIBILD, SYMDEKO, SYMTUZA, TAGRISSO, TAVALISSE, TEPMETKO, TOLSURA, TRANDOLAPRIL-VERAPAMIL ER, TRIKAFTA, TUKYSA, TYBOST, TYKERB, VERAPAMIL ER, VERAPAMIL ER PM, VERAPAMIL HCL, VERAPAMIL SR, VOQUEZNA TRIPLE PAK, VOSEVI, VOYDEYA, XOLREMDI, ZELBORAF, ZITHROMAX, ZITHROMAX TRI-PAK, ZOKINVY |
| Afatinib/P-glycoprotein (P-gp) Inducers; Phenobarbital SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Afatinib is a substrate of the intestinal efflux transporter P-glycoprotein (P-gp). Apalutamide, carbamazepine, efavirenz, lorlatinib, phenytoin, rifabutin, rifampin, rifapentine, and St. John's wort induce production of P-gp which may lead to decreased exposure to afatinib.(1,2) Phenobarbital may also induce the metabolism of afatinib.(1) Primidone is metabolized to phenobarbital. CLINICAL EFFECTS: Concurrent or recent use of P-glycoprotein inducers (apalutamide, carbamazepine, efavirenz, lorlatinib, phenytoin, rifabutin, rifampin, rifapentine, or St. John's wort), phenobarbital, or primidone may result in decreased levels and effectiveness of afatinib. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of afatinib recommends an increase of afatinib dose by 10 mg per day as tolerated in patients receiving chronic therapy with a P-gp inducer or phenobarbital.(1) Onset of induction is gradual and maximal induction may be delayed for many days or longer, depending upon the inducing agent and dose. If the P-gp inducer, phenobarbital, or primidone is stopped, the manufacturer of afatinib recommends resumption of previous afatinib dose 2 to 3 days after discontinuation of the inducing agent.(1) DISCUSSION: In a drug interaction study, co-administration of rifampin 600 mg once daily for 7 days decreased afatinib exposure 34%.(1) P-gp inducers include apalutamide, carbamazepine, efavirenz, lorlatinib, phenytoin, rifabutin, rifampin, rifapentine, and St. John's wort.(1,2) Based on 2 case reports(3,4) and in vitro studies,(5,6) the manufacturer of afatinib also includes phenobarbital as a P-gp inducer.(1) |
CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DILANTIN, DILANTIN-125, DONNATAL, EFAVIRENZ, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, EPITOL, EQUETRO, ERLEADA, FOSPHENYTOIN SODIUM, LORBRENA, MYSOLINE, PHENOBARBITAL, PHENOBARBITAL SODIUM, PHENOBARBITAL-BELLADONNA, PHENOBARBITAL-HYOSC-ATROP-SCOP, PHENOHYTRO, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, PRIFTIN, PRIMIDONE, RIFABUTIN, RIFADIN, RIFAMPIN, SEZABY, SYMFI, SYMFI LO, TALICIA, TEGRETOL, TEGRETOL XR |
The following contraindication information is available for GILOTRIF (afatinib dimaleate):
Drug contraindication overview.
The manufacturer states there are no known contraindications to the use of afatinib.
The manufacturer states there are no known contraindications to the use of afatinib.
There are 1 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Lactation |
There are 8 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Diverticulitis of gastrointestinal tract |
| Drug-induced hepatitis |
| Gastrointestinal ulcer |
| Interstitial lung disease |
| Left ventricular failure |
| Pregnancy |
| Severe diarrhea |
There are 1 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Keratitis |
The following adverse reaction information is available for GILOTRIF (afatinib dimaleate):
Adverse reaction overview.
The most common adverse reactions (>=20%) in patients receiving afatinib include diarrhea, rash/acneiform dermatitis, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, and pruritus.
The most common adverse reactions (>=20%) in patients receiving afatinib include diarrhea, rash/acneiform dermatitis, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, and pruritus.
There are 26 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Abnormal hepatic function tests |
Anemia Cellulitis Dehydration Gastrointestinal perforation Increased alanine transaminase Interstitial lung disease Left ventricular failure Leukopenia Myocardial dysfunction Palmar-plantar erythrodysesthesia Severe diarrhea |
| Rare/Very Rare |
|---|
|
Acute respiratory failure Bacterial sepsis Bullous dermatitis Dyspnea Exfoliative dermatitis Hepatic failure Hypersensitivity pneumonitis Hypokalemia Interstitial pneumonitis Keratitis Pancreatitis Pneumonia Stevens-johnson syndrome Toxic epidermal necrolysis |
There are 46 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acneiform eruption Anorexia Diarrhea Dry skin Erythema Nausea Paronychia Pruritus of skin Skin rash Stomatitis Vomiting |
Abdominal distension Acute abdominal pain Alopecia Arthralgia Back pain Blepharitis Cheilitis Conjunctivitis Constipation Cough Cystitis Dizziness Dysesthesia Dysphagia Epistaxis Fever Gastritis Gastroesophageal reflux disease Glossitis Headache disorder Hirsutism Muscle spasm Musculoskeletal pain Myalgia Nail disorders Pharyngitis Phototoxicity Proteinuria Rectal pain Rhinorrhea Skin fissure Skin pigmentation enhancement Upper respiratory infection Weight loss |
| Rare/Very Rare |
|---|
|
Fatigue |
The following precautions are available for GILOTRIF (afatinib dimaleate):
Safety and efficacy of afatinib have not been established in pediatric patients.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Afatinib may cause fetal harm if administered to pregnant women based on its mechanism of action and animal findings.
Afatinib is distributed into milk in rats; it is not known whether the drug is distributed into milk in humans or if the drug has any effect on milk production or the nursing infant. Because of the potential for serious adverse reactions to afatinib in nursing infants, women should be advised to discontinue nursing while receiving the drug and for 2 weeks after the drug is discontinued.
The LUX-Lung 3 study evaluating afatinib in patients with previously untreated metastatic NSCLC did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger adults. In subgroup analyses of 3 clinical studies, including LUX-Lung 3, evaluating afatinib as first-line therapy in patients with EGFR mutation-positive NSCLC, efficacy of afatinib in patients 65 years of age and older was consistent with that observed in the overall study population. In the LUX-Lung 8 study evaluating afatinib in patients with previously treated metastatic squamous NSCLC, 53% of patients were 65 years of age or older and 11% were 75 years of age or older.
In an exploratory subgroup analysis, afatinib reduced the risk of death by 5% in patients 65 years of age and older and 32% in those younger than 65 years of age. No overall differences in safety were observed between geriatric patients and younger adults.
In an exploratory subgroup analysis, afatinib reduced the risk of death by 5% in patients 65 years of age and older and 32% in those younger than 65 years of age. No overall differences in safety were observed between geriatric patients and younger adults.
The following prioritized warning is available for GILOTRIF (afatinib dimaleate):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for GILOTRIF (afatinib dimaleate)'s list of indications:
| EGFR positive non-small cell lung cancer | |
| C34 | Malignant neoplasm of bronchus and lung |
| C34.0 | Malignant neoplasm of main bronchus |
| C34.00 | Malignant neoplasm of unspecified main bronchus |
| C34.01 | Malignant neoplasm of right main bronchus |
| C34.02 | Malignant neoplasm of left main bronchus |
| C34.1 | Malignant neoplasm of upper lobe, bronchus or lung |
| C34.10 | Malignant neoplasm of upper lobe, unspecified bronchus or lung |
| C34.11 | Malignant neoplasm of upper lobe, right bronchus or lung |
| C34.12 | Malignant neoplasm of upper lobe, left bronchus or lung |
| C34.2 | Malignant neoplasm of middle lobe, bronchus or lung |
| C34.3 | Malignant neoplasm of lower lobe, bronchus or lung |
| C34.30 | Malignant neoplasm of lower lobe, unspecified bronchus or lung |
| C34.31 | Malignant neoplasm of lower lobe, right bronchus or lung |
| C34.32 | Malignant neoplasm of lower lobe, left bronchus or lung |
| C34.8 | Malignant neoplasm of overlapping sites of bronchus and lung |
| C34.80 | Malignant neoplasm of overlapping sites of unspecified bronchus and lung |
| C34.81 | Malignant neoplasm of overlapping sites of right bronchus and lung |
| C34.82 | Malignant neoplasm of overlapping sites of left bronchus and lung |
| C34.9 | Malignant neoplasm of unspecified part of bronchus or lung |
| C34.90 | Malignant neoplasm of unspecified part of unspecified bronchus or lung |
| C34.91 | Malignant neoplasm of unspecified part of right bronchus or lung |
| C34.92 | Malignant neoplasm of unspecified part of left bronchus or lung |
| C39.9 | Malignant neoplasm of lower respiratory tract, part unspecified |
| Squamous cell carcinoma of lung | |
| C34 | Malignant neoplasm of bronchus and lung |
| C34.0 | Malignant neoplasm of main bronchus |
| C34.00 | Malignant neoplasm of unspecified main bronchus |
| C34.01 | Malignant neoplasm of right main bronchus |
| C34.02 | Malignant neoplasm of left main bronchus |
| C34.1 | Malignant neoplasm of upper lobe, bronchus or lung |
| C34.10 | Malignant neoplasm of upper lobe, unspecified bronchus or lung |
| C34.11 | Malignant neoplasm of upper lobe, right bronchus or lung |
| C34.12 | Malignant neoplasm of upper lobe, left bronchus or lung |
| C34.2 | Malignant neoplasm of middle lobe, bronchus or lung |
| C34.3 | Malignant neoplasm of lower lobe, bronchus or lung |
| C34.30 | Malignant neoplasm of lower lobe, unspecified bronchus or lung |
| C34.31 | Malignant neoplasm of lower lobe, right bronchus or lung |
| C34.32 | Malignant neoplasm of lower lobe, left bronchus or lung |
| C34.8 | Malignant neoplasm of overlapping sites of bronchus and lung |
| C34.80 | Malignant neoplasm of overlapping sites of unspecified bronchus and lung |
| C34.81 | Malignant neoplasm of overlapping sites of right bronchus and lung |
| C34.82 | Malignant neoplasm of overlapping sites of left bronchus and lung |
| C34.9 | Malignant neoplasm of unspecified part of bronchus or lung |
| C34.90 | Malignant neoplasm of unspecified part of unspecified bronchus or lung |
| C34.91 | Malignant neoplasm of unspecified part of right bronchus or lung |
| C34.92 | Malignant neoplasm of unspecified part of left bronchus or lung |
Formulary Reference Tool