Afatinib is an orally bioavailable anilino-quinazoline derivative and inhibitor of the receptor tyrosine kinase (RTK) epidermal growth factor receptor (ErbB; EGFR) family, with antineoplastic activity. Afatinib is a maleate salt obtained by combining afatinib with two molar equivalents of maleic acid. Upon administration, afatinib selectively and irreversibly binds to and inhibits the epidermal growth factor receptors 1 (ErbB1; EGFR), 2 (ErbB2; HER2), and 4 (ErbB4; HER4), and certain EGFR mutants, including those caused by EGFR exon 19 deletion mutations or exon 21 (L858R) mutations. This may result in the inhibition of tumor growth and angiogenesis in tumor cells overexpressing these RTKs. Additionally, afatinib inhibits the EGFR T790M gatekeeper mutation which is resistant to treatment with first-generation EGFR inhibitors. EGFR, HER2, and HER4 are RTKs that belong to the EGFR superfamily; they play major roles in both tumor cell proliferation and tumor vascularization and are overexpressed in many cancer cell types.
Afatinib is a tyrosine kinase receptor inhibitor that is used in the therapy of selected forms of metastatic non-small cell lung cancer. Afatinib is associated with transient elevations in serum aminotransferase levels during therapy and has been reported to cause clinically apparent acute liver injury and rare instances of death.
Afatinib dimaleate is the dimaleate salt form of afatinib, an orally bioavailable anilino-quinazoline derivative and inhibitor of the receptor tyrosine kinase (RTK) epidermal growth factor receptor (ErbB; EGFR) family, with antineoplastic activity. Upon administration, afatinib selectively and irreversibly binds to and inhibits the epidermal growth factor receptors 1 (ErbB1; EGFR), 2 (ErbB2; HER2), and 4 (ErbB4; HER4), and certain EGFR mutants, including those caused by EGFR exon 19 deletion mutations or exon 21 (L858R) mutations. This may result in the inhibition of tumor growth and angiogenesis in tumor cells overexpressing these RTKs. Additionally, afatinib inhibits the EGFR T790M gatekeeper mutation which is resistant to treatment with first-generation EGFR inhibitors. EGFR, HER2, and HER4 are RTKs that belong to the EGFR superfamily; they play major roles in both tumor cell proliferation and tumor vascularization and are overexpressed in many cancer cell types.
Afatinib is a quinazoline compound having a 3-chloro-4-fluoroanilino group at the 4-position, a 4-dimethylamino-trans-but-2-enamido group at the 6-position, and an (S)-tetrahydrofuran-3-aryloxy group at the 7-position. Used (as its dimaleate salt) for the first-line treatment of patients with metastatic non-small cell lung cancer. It has a role as a tyrosine kinase inhibitor and an antineoplastic agent. It is a member of quinazolines, a member of furans, an organofluorine compound, an enamide, an aromatic ether, a tertiary amine compound, a member of monochlorobenzenes and a secondary carboxamide.
Recently, as of January 2018, the US FDA approved a supplemental New Drug Application for Boehringer Ingelheim’s Gilotrif (afatinib) for the first line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test [rx]. The new label includes data on three additional EGFR mutations: L861Q, G719X and S768I rx].
Mechanism of Action
Afatinib is a potent and selective, irreversible ErbB family blocker. Afatinib covalently binds to and irreversibly blocks signaling from all homo and heterodimers formed by the ErbB family members EGFR (ErbB1), HER2 (ErbB2), ErbB3 and ErbB4. In particular, afatinib 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 signaling. Certain mutations in EGFR, including non-resistant mutations in its kinase domain, can result in increased autophosphorylation of the receptor, leading to receptor activation, sometimes in the absence of ligand binding, and can support cell proliferation in NSCLC. Non-resistant mutations are defined as those occurring in exons constituting the kinase domain of EGFR that lead to increased receptor activation and where efficacy is predicted by 1) clinically meaningful tumor shrinkage with the recommended dose of afatinib and/or 2) inhibition of cellular proliferation or EGFR tyrosine kinase phosphorylation at concentrations of afatinib sustainable at the recommended dosage according to validated methods. The most commonly found of these mutations are exon 21 L858R substitutions and exon 19 deletions. Moreover, afatinib demonstrated inhibition of autophosphorylation and/or in vitro proliferation of cell lines expressing wild-type EGFR and in those expressing selected EGFR exon 19 deletion mutations, exon 21 L858R mutations, or other less common non-resistant mutations, at afatinib concentrations achieved in patients. In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2.
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Afatinib covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in the downregulation of ErbB signaling. Certain mutations in EGFR, including non-resistant mutations in its kinase domain, can result in increased autophosphorylation of the receptor, leading to receptor activation, sometimes in the absence of ligand binding, and can support cell proliferation in NSCLC. Non-resistant mutations are defined as those occurring in exons constituting the kinase domain of EGFR that lead to increased receptor activation and where efficacy is predicted by 1) clinically meaningful tumor shrinkage with the recommended dose of afatinib and/or 2) inhibition of cellular proliferation or EGFR tyrosine kinase phosphorylation at concentrations of afatinib sustainable at the recommended dosage according to validated methods. The most commonly found of these mutations are exon 21 L858R substitutions and exon 19 deletions. Afatinib demonstrated inhibition of autophosphorylation and/or in vitro proliferation of cell lines expressing wild-type EGFR and in those expressing selected EGFR exon 19 deletion mutations, exon 21 L858R mutations, or other less common non-resistant mutations, at afatinib concentrations achieved in patients. In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2. Treatment with afatinib resulted in the inhibition of tumor growth in nude mice implanted with tumors either overexpressing wild-type EGFR or HER2 or in an EGFR L858R/T790M double mutant model.
Indications
- Afatinib is a kinase inhibitor indicated as monotherapy for the first-line treatment of (a) Epidermal Growth Factor Receptor (EGFR) TKI (tyrosine kinase inhibitor)-naive adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant EGFR mutations as detected by an FDA-approved test, and (b) adult patients with locally advanced or metastatic NSCLC of squamous histology progressing on or after platinum-based chemotherapy. Recently, as of January 2018, the US FDA approved a supplemental New Drug Application for Boehringer Ingelheim’s Gilotrif (afatinib) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test. The new label includes data on three additional EGFR mutations: L861Q, G719X, and S768I.
- Giotrif as monotherapy is indicated for the treatment of Epidermal Growth Factor Receptor (EGFR) TKI-naïve adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation(s); locally advanced or metastatic NSCLC of squamous histology progressing on or after platinum-based chemotherapy.
- Treatment of all conditions included in the category of malignant neoplasms (excluding central nervous system, hematopoietic and lymphoid tissue neoplasms), Treatment of malignant neoplasms of the central nervous system.
- Afatinib is a kinase inhibitor indicated as monotherapy for the first-line treatment of (a) Epidermal Growth Factor Receptor (EGFR) TKI (tyrosine kinase inhibitor)-naive adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumours have non-resistant EGFR mutations as detected by an FDA-approved test and (b) adult patients with locally advanced or metastatic NSCLC of squamous histology progressing on or after platinum-based chemotherapy [rx].
- EGFR Mutation-Positive, Metastatic Non-Small Cell Lung Cancer: For the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an approved test.
- Previously Treated, Metastatic Squamous NSCLC: For the treatment of patients with metastatic squamous NSCLC progressing after platinum-based chemotherapy.
- Metastatic Non-Small Cell Lung Cancer
- Refractory, metastatic squamous cell Non-small cell lung cancer
Use in Cancer
Afatinib dimaleate is approved to treat:
- Non-small cell lung cancer (NSCLC) that has metastasized (spread to other parts of the body). It is used:
Afatinib dimaleate is also being studied in the treatment of other types of cancer.
Contraindications
- Any life-threatening bullous, blistering, or exfoliative skin lesions.
- Confirmed interstitial lung disease (ILD)
- Severe drug-induced hepatic impairment.
- Persistent ulcerative keratitis.
- Symptomatic left ventricle dysfunction.
- Severe or intolerable adverse reaction occurring at a dose of 20 mg per day.
- inflammation of the cornea of the eye
- left ventricular heart failure
- stomach or intestinal ulcer
- diverticulitis
- damage to the liver and inflammation
- excessive diarrhea
- pregnancy
- a patient who is producing milk and breastfeeding
- lung tissue problem
- chronic kidney disease stage 4 (severe)
Dosage
Strengths: 30 mg; 40 mg; 20 mg
Non-Small Cell Lung Cancer
- 40 mg orally once a day until disease progression or intolerance by the patient
- Take on an empty stomach at least 1 hour before or 2 hours after a meal.
- Epidermal growth factor receptor (EGFR) mutation status should be established prior to therapy initiation.
- Do not take a missed dose within 12 hours of the next dose.
Renal Dose Adjustments
- Mild to moderate renal impairment (CrCl 30 mL/min or greater): No adjustment recommended.
- Severe renal impairment (CrCl 15 to 29 mL/min): 30 mg orally once a day
- End stage renal disease (CrCl less than 15 mL/min) or dialysis: Data not available
Liver Dose Adjustments
- Mild (Child-Pugh A) to moderate (Child-Pugh B) hepatic impairment: No adjustment recommended.
- Severe (Child-Pugh C) hepatic impairment: Closely monitor the patient and adjust the dose if not tolerated.
Dose Adjustments
Dose Modifications for Adverse Reactions:
WITHHOLD THERAPY FOR:
- National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 3 or higher.
- Diarrhea Grade 2 or higher persisting for 2 or more consecutive days while taking antidiarrheal medication.
- Cutaneous reactions of Grade 2 that are prolonged (lasting more than 7 days) or intolerable.
- Renal impairment Grade 2 or higher
Resume therapy when the adverse reaction fully resolves, returns to baseline, or improves to Grade 1. Reinstitute therapy at a reduced dose (e.g., 10 mg per day less than the dose at which the adverse reaction occurred).
PERMANENTLY DISCONTINUE THERAPY FOR:
- Life-threatening bullous, blistering, or exfoliative skin lesions
- Confirmed interstitial lung disease (ILD)
- Severe drug-induced hepatic impairment
- Persistent ulcerative keratitis
- Symptomatic left ventricular dysfunction
- The severe or intolerable adverse reactions occurring at a dose of 20 mg per day
Dose Modifications for Drug Interactions:
- P-gp Inhibitors: Reduce the daily dose by 10 mg if not tolerated for patients who require therapy with a P-glycoprotein (P-gp) inhibitor. Resume the previous dose after discontinuation of the P-gp inhibitor as tolerated.
- P-gp Inducers: Increase the daily dose by 10 mg as tolerated for patients who require chronic therapy with a P-gp inducer. Resume the previous dose 2 to 3 days after discontinuation of the P-gp inducer.
Administration advice:
- Swallow tablets whole with water.
- In case of swallowing difficulties, the tablets may be dispersed (not crushed) in approximately 100 mL of noncarbonated water. The dispersion may also be given via a gastric tube.
- Take on an empty stomach.
- Do not take a missed dose within 12 hours of the next dose.
Side Effects
The Most Common
- cracking or swelling of the lips or sores in the corners of the mouth
- dry skin or itching
- loss of appetite
- nail infection
- acne
- nose bleeds
- diarrhea
- dry mouth, dark urine, decreased sweating, dry skin, and other signs of dehydration
- decreased urination
- swelling of the arms, hands, feet, ankles, or lower legs
- rash
- pain, redness, peeling, or blistering of skin
- difficulty breathing
- shortness of breath
- rapid, irregular, or pounding heartbeat
- sudden weight gain
- cough
- fever
- excessive tiredness
- pain in the right upper part of the stomach
- unusual bruising or bleeding
- nausea
- vomiting
- yellowing of the skin or eyes
- dark urine
- red, swollen, painful, or teary eyes
- sudden changes in vision, including blurred vision
- sensitivity to light
More common
- Bloody or cloudy urine
- burning, dry, or itching eyes
- diarrhea
- difficult, burning, or painful urination
- discharge or excessive tearing
- fever
- frequent urge to urinate
- redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid
- redness, swelling, or pain of the skin
- scaling of the skin on the hands and feet
- tingling of the hands and feet
- ulceration of the skin
- Cough
- difficult breathing
- Blemishes on the skin
- canker sores
- chapped, red, or swollen lips
- decreased appetite
- decreased weight
- dry skin
- itching skin or rash
- loosening of the fingernails
- nosebleeds
- pimples
- redness or soreness around the fingernails
- runny nose
- scaling, redness, burning, pain, or other signs of inflammation of the lips
- sores, ulcers, or white spots on the lips or tongue or inside the mouth
Rare
- Bloody, black, or tarry stools
- heartburn
- indigestion
- nausea
- severe abdominal pain, cramping, or burning
- vomiting of material that looks like coffee grounds, severe and continuing
- Dizziness
- headache
- lack or loss of strength
- stomach pain
- vomiting
Drug Interactions
| DRUG | INTERACTION |
|---|---|
| Abaloparatide | The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Afatinib. |
| Abemaciclib | The serum concentration of Abemaciclib can be increased when it is combined with Afatinib. |
| Abrocitinib | The serum concentration of Afatinib can be increased when it is combined with Abrocitinib. |
| Acetaminophen | The serum concentration of Acetaminophen can be increased when it is combined with Afatinib. |
| Alectinib | Alectinib may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Allopurinol | Afatinib may decrease the excretion rate of Allopurinol which could result in a higher serum level. |
| Alpelisib | The serum concentration of Alpelisib can be increased when it is combined with Afatinib. |
| Ambrisentan | The serum concentration of Ambrisentan can be increased when it is combined with Afatinib. |
| Amiodarone | The serum concentration of Afatinib can be increased when it is combined with Amiodarone. |
| Apalutamide | The serum concentration of Afatinib can be decreased when it is combined with Apalutamide. |
| Apixaban | Afatinib may decrease the excretion rate of Apixaban which could result in a higher serum level. |
| Arsenic trioxide | The serum concentration of Afatinib can be increased when it is combined with Arsenic trioxide. |
| Articaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Articaine. |
| Asciminib | The serum concentration of Afatinib can be increased when it is combined with Asciminib. |
| Asunaprevir | The serum concentration of Afatinib can be increased when it is combined with Asunaprevir. |
| Avanafil | Avanafil may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Avatrombopag | Avatrombopag may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Axitinib | The serum concentration of Axitinib can be increased when it is combined with Afatinib. |
| Beclomethasone | Beclomethasone dipropionate may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Belantamab | The serum concentration of Belantamab mafodotin can be increased when it is combined with Afatinib. |
| Belinostat | The serum concentration of Belinostat can be increased when it is combined with Afatinib. |
| Belumosudil | The serum concentration of Afatinib can be increased when it is combined with Belumosudil. |
| Bendamustine | The serum concentration of Bendamustine can be increased when it is combined with Afatinib. |
| Benzocaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Benzocaine. |
| Benzyl alcohol | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Benzyl alcohol. |
| Berotralstat | The serum concentration of Berotralstat can be increased when it is combined with Afatinib. |
| Betrixaban | The serum concentration of Betrixaban can be increased when it is combined with Afatinib. |
| Binimetinib | The serum concentration of Binimetinib can be increased when it is combined with Afatinib. |
| Bisoprolol | The serum concentration of Bisoprolol can be increased when it is combined with Afatinib. |
| Bortezomib | The serum concentration of Bortezomib can be increased when it is combined with Afatinib. |
| Bosutinib | The serum concentration of Bosutinib can be increased when it is combined with Afatinib. |
| Brentuximab | The serum concentration of Brentuximab vedotin can be increased when it is combined with Afatinib. |
| Brigatinib | Afatinib may decrease the excretion rate of Brigatinib which could result in a higher serum level. |
| Bupivacaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Bupivacaine. |
| Buprenorphine | Buprenorphine may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Butacaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Butacaine. |
| Butamben | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Butamben. |
| Cabazitaxel | The serum concentration of Cabazitaxel can be increased when it is combined with Afatinib. |
| Cabergoline | The serum concentration of Cabergoline can be increased when it is combined with Afatinib. |
| Caffeine | Caffeine may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Canagliflozin | The serum concentration of Afatinib can be increased when it is combined with Canagliflozin. |
| Cannabidiol | Cannabidiol may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Capmatinib | The serum concentration of Afatinib can be increased when it is combined with Capmatinib. |
| Capsaicin | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Capsaicin. |
| Carbimazole | The therapeutic efficacy of Carbimazole can be decreased when used in combination with Afatinib. |
| Carfilzomib | The serum concentration of Afatinib can be increased when it is combined with Carfilzomib. |
| Carvedilol | The serum concentration of Afatinib can be increased when it is combined with Carvedilol. |
| Celecoxib | Afatinib may decrease the excretion rate of Celecoxib which could result in a higher serum level. |
| Ceritinib | The serum concentration of Ceritinib can be increased when it is combined with Afatinib. |
| Cerivastatin | Afatinib may decrease the excretion rate of Cerivastatin which could result in a higher serum level. |
| Chloroprocaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Chloroprocaine. |
| Cholesterol | Cholesterol may increase the excretion rate of Afatinib which could result in a lower serum level and potentially a reduction in efficacy. |
| Cinchocaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Cinchocaine. |
| Cladribine | Afatinib may decrease the excretion rate of Cladribine which could result in a higher serum level. |
| Clarithromycin | The serum concentration of Afatinib can be increased when it is combined with Clarithromycin. |
| Clobazam | The serum concentration of Clobazam can be increased when it is combined with Afatinib. |
| Clofarabine | Afatinib may decrease the excretion rate of Clofarabine which could result in a higher serum level. |
| Clofazimine | The serum concentration of Afatinib can be increased when it is combined with Clofazimine. |
| Clomifene | The serum concentration of Clomifene can be increased when it is combined with Afatinib. |
| Cobicistat | The serum concentration of Afatinib can be increased when it is combined with Cobicistat. |
| Cobimetinib | The serum concentration of Cobimetinib can be increased when it is combined with Afatinib. |
| Cocaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Cocaine. |
| Colchicine | The serum concentration of Colchicine can be increased when it is combined with Afatinib. |
| Conivaptan | The serum concentration of Afatinib can be increased when it is combined with Conivaptan. |
| C. estrogens | Afatinib may decrease the excretion rate of Conjugated estrogens which could result in a higher serum level. |
| Copanlisib | The serum concentration of Copanlisib can be increased when it is combined with Afatinib. |
| Crizotinib | The serum concentration of Afatinib can be increased when it is combined with Crizotinib. |
| Curcumin | The serum concentration of Afatinib can be increased when it is combined with Curcumin. |
| Cyclosporine | The serum concentration of Afatinib can be increased when it is combined with Cyclosporine. |
| Dabigatran | The serum concentration of Dabigatran etexilate can be increased when it is combined with Afatinib. |
| Dabrafenib | The serum concentration of Dabrafenib can be increased when it is combined with Afatinib. |
| Daclatasvir | The serum concentration of Afatinib can be increased when it is combined with Daclatasvir. |
| Dacomitinib | The serum concentration of Afatinib can be increased when it is combined with Dacomitinib. |
| Dactinomycin | The serum concentration of Dactinomycin can be increased when it is combined with Afatinib. |
| Daptomycin | The serum concentration of Daptomycin can be increased when it is combined with Afatinib. |
| Darbepoetin alfa | The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Afatinib. |
| Darolutamide | The serum concentration of Afatinib can be increased when it is combined with Darolutamide. |
| Darunavir | The serum concentration of Darunavir can be increased when it is combined with Afatinib. |
| Dasabuvir | Dasabuvir may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Dasatinib | The serum concentration of Dasatinib can be increased when it is combined with Afatinib. |
| Daunorubicin | Afatinib may decrease the excretion rate of Daunorubicin which could result in a higher serum level. |
| Delafloxacin | Afatinib may decrease the excretion rate of Delafloxacin which could result in a higher serum level. |
| Dexamethasone | Dexamethasone may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Dexamethasone | The serum concentration of Afatinib can be decreased when it is combined with Dexamethasone acetate. |
| Diethylstilbestrol | Diethylstilbestrol may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Digitoxin | The serum concentration of Digitoxin can be increased when it is combined with Afatinib. |
| Digoxin | Afatinib may decrease the excretion rate of Digoxin which could result in a higher serum level. |
| Diosmin | The serum concentration of Afatinib can be increased when it is combined with Diosmin. |
| Diphenhydramine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Diphenhydramine. |
| Dolutegravir | Afatinib may decrease the excretion rate of Dolutegravir which could result in a higher serum level. |
| Donepezil | Afatinib may decrease the excretion rate of Donepezil which could result in a higher serum level. |
| Doxorubicin | The serum concentration of Doxorubicin can be increased when it is combined with Afatinib. |
| Dronedarone | The serum concentration of Afatinib can be increased when it is combined with Dronedarone. |
| Duvelisib | Afatinib may decrease the excretion rate of Duvelisib which could result in a higher serum level. |
| Dyclonine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Dyclonine. |
| Edoxaban | The serum concentration of Edoxaban can be increased when it is combined with Afatinib. |
| Elagolix | The serum concentration of Afatinib can be increased when it is combined with Elagolix. |
| Elbasvir | Elbasvir may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Eliglustat | The serum concentration of Afatinib can be increased when it is combined with Eliglustat. |
| Eltrombopag | Eltrombopag may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Enasidenib | The serum concentration of Afatinib can be increased when it is combined with Enasidenib. |
| Enfortumab | The serum concentration of Enfortumab vedotin can be increased when it is combined with Afatinib. |
| Entrectinib | The serum concentration of Afatinib can be increased when it is combined with Entrectinib. |
| Erdafitinib | The serum concentration of Afatinib can be increased when it is combined with Erdafitinib. |
| Erlotinib | Erlotinib may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Ertugliflozin | Afatinib may decrease the excretion rate of Ertugliflozin which could result in a higher serum level. |
| Erythromycin | The serum concentration of Afatinib can be increased when it is combined with Erythromycin. |
| Erythropoietin | The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Afatinib. |
| Estradiol | Estradiol may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Estradiol acetate | Estradiol acetate may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Estradiol benzoate | Estradiol benzoate may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Estradiol cypionate | Estradiol cypionate may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Estradiol | Estradiol dienanthate may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Estradiol valerate | Estradiol valerate may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Ethyl chloride | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Ethyl chloride. |
| Etidocaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Etidocaine. |
| Etoposide | The serum concentration of Etoposide can be increased when it is combined with Afatinib. |
| Everolimus | The serum concentration of Afatinib can be increased when it is combined with Everolimus. |
| Ezetimibe | Afatinib may decrease the excretion rate of Ezetimibe which could result in a higher serum level. |
| Favipiravir | The serum concentration of Afatinib can be increased when it is combined with Favipiravir. |
| Febuxostat | The excretion of Afatinib can be decreased when combined with Febuxostat. |
| Fedratinib | The serum concentration of Afatinib can be increased when it is combined with Fedratinib. |
| Fexofenadine | The serum concentration of Fexofenadine can be increased when it is combined with Afatinib. |
| Flibanserin | The serum concentration of Afatinib can be increased when it is combined with Flibanserin. |
| Fluconazole | The serum concentration of Afatinib can be increased when it is combined with Fluconazole. |
| Fluorouracil | Afatinib may decrease the excretion rate of Fluorouracil which could result in a higher serum level. |
| Folic acid | Afatinib may decrease the excretion rate of Folic acid which could result in a higher serum level. |
| Follitropin | The therapeutic efficacy of Follitropin can be decreased when used in combination with Afatinib. |
| Fostamatinib | Fostamatinib may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Fostemsavir | Afatinib may decrease the excretion rate of Fostemsavir which could result in a higher serum level. |
| Fusidic acid | Fusidic acid may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Futibatinib | The serum concentration of Futibatinib can be increased when it is combined with Afatinib. |
| Gefitinib | Gefitinib may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Gemcitabine | The serum concentration of Gemcitabine can be increased when it is combined with Afatinib. |
| Gilteritinib | Gilteritinib may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Glasdegib | The serum concentration of Afatinib can be increased when it is combined with Glasdegib. |
| Glecaprevir | The serum concentration of Afatinib can be increased when it is combined with Glecaprevir. |
| Glyburide | Afatinib may decrease the excretion rate of Glyburide which could result in a higher serum level. |
| Grazoprevir | Grazoprevir may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Idelalisib | Afatinib may decrease the excretion rate of Idelalisib which could result in a higher serum level. |
| Imatinib | Imatinib may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Imipramine | The serum concentration of Imipramine can be increased when it is combined with Afatinib. |
| Indacaterol | The serum concentration of Indacaterol can be increased when it is combined with Afatinib. |
| Inotuzumab | The serum concentration of Inotuzumab ozogamicin can be increased when it is combined with Afatinib. |
| Irinotecan | Afatinib may decrease the excretion rate of Irinotecan which could result in a higher serum level. |
| Isavuconazole | The serum concentration of Afatinib can be increased when it is combined with Isavuconazole. |
| Isavuconazonium | The serum concentration of Afatinib can be increased when it is combined with Isavuconazonium. |
| Istradefylline | The serum concentration of Afatinib can be increased when it is combined with Istradefylline. |
| Itraconazole | The serum concentration of Afatinib can be increased when it is combined with Itraconazole. |
| Ivacaftor | The serum concentration of Afatinib can be increased when it is combined with Ivacaftor. |
| Ivermectin | Afatinib may decrease the excretion rate of Ivermectin which could result in a higher serum level. |
| Ixabepilone | The serum concentration of Afatinib can be increased when it is combined with Ixabepilone. |
| Ketoconazole | The serum concentration of Afatinib can be increased when it is combined with Ketoconazole. |
| Lamivudine | Afatinib may decrease the excretion rate of Lamivudine which could result in a higher serum level. |
| Lansoprazole | Lansoprazole may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Lapatinib | The serum concentration of Afatinib can be increased when it is combined with Lapatinib. |
| Larotrectinib | The serum concentration of Larotrectinib can be increased when it is combined with Afatinib. |
| Lasmiditan | The serum concentration of Afatinib can be increased when it is combined with Lasmiditan. |
| Ledipasvir | The serum concentration of Ledipasvir can be increased when it is combined with Afatinib. |
| Lefamulin | Afatinib may decrease the excretion rate of Lefamulin which could result in a higher serum level. |
| Leflunomide | Afatinib may decrease the excretion rate of Leflunomide which could result in a higher serum level. |
| Lemborexant | The serum concentration of Lemborexant can be increased when it is combined with Afatinib. |
| Lenvatinib | Afatinib may decrease the excretion rate of Lenvatinib which could result in a higher serum level. |
| Letermovir | Letermovir may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Levobupivacaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Levobupivacaine. |
| Levoketoconazole | The serum concentration of Afatinib can be increased when it is combined with Levoketoconazole. |
| Levothyroxine | The serum concentration of Afatinib can be decreased when it is combined with Levothyroxine. |
| Lidocaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Lidocaine. |
| Linagliptin | The serum concentration of Afatinib can be increased when it is combined with Linagliptin. |
| Liothyronine | The therapeutic efficacy of Liothyronine can be decreased when used in combination with Afatinib. |
| Liotrix | The therapeutic efficacy of Liotrix can be decreased when used in combination with Afatinib. |
| Lomitapide | The serum concentration of Afatinib can be increased when it is combined with Lomitapide. |
| Lonafarnib | The serum concentration of Afatinib can be increased when it is combined with Lonafarnib. |
| Loncastuximab | The serum concentration of Loncastuximab tesirine can be increased when it is combined with Afatinib. |
| Loperamide | The excretion of Loperamide can be decreased when combined with Afatinib. |
| Lopinavir | The serum concentration of Afatinib can be increased when it is combined with Lopinavir. |
| Lorlatinib | The serum concentration of Afatinib can be decreased when it is combined with Lorlatinib. |
| Loxapine | The serum concentration of Afatinib can be increased when it is combined with Loxapine. |
| Lumacaftor | The serum concentration of Afatinib can be increased when it is combined with Lumacaftor. |
| Lusutrombopag | Afatinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level. |
| Mannitol | The serum concentration of Mannitol can be increased when it is combined with Afatinib. |
| Maribavir | The serum concentration of Afatinib can be increased when it is combined with Maribavir. |
| Mefloquine | The serum concentration of Afatinib can be increased when it is combined with Mefloquine. |
| Meloxicam | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Meloxicam. |
| Mepivacaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Mepivacaine. |
| Methimazole | The therapeutic efficacy of Methimazole can be decreased when used in combination with Afatinib. |
| Methotrexate | Afatinib may decrease the excretion rate of Methotrexate which could result in a higher serum level. |
| Methoxy | The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Afatinib. |
| Methylene blue | The serum concentration of Afatinib can be increased when it is combined with Methylene blue. |
| Mifepristone | The serum concentration of Afatinib can be increased when it is combined with Mifepristone. |
| Mirabegron | The serum concentration of Afatinib can be increased when it is combined with Mirabegron. |
| Mitapivat | The serum concentration of Afatinib can be increased when it is combined with Mitapivat. |
| Mitoxantrone | Afatinib may decrease the excretion rate of Mitoxantrone which could result in a higher serum level. |
| Morphine | The serum concentration of Morphine can be increased when it is combined with Afatinib. |
| Mycophenolate | Afatinib may decrease the excretion rate of Mycophenolate mofetil which could result in a higher serum level. |
| Naloxegol | The serum concentration of Naloxegol can be increased when it is combined with Afatinib. |
| Nelfinavir | Nelfinavir may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Neratinib | The serum concentration of Afatinib can be increased when it is combined with Neratinib. |
| Netupitant | The serum concentration of Afatinib can be increased when it is combined with Netupitant. |
| Nilotinib | The serum concentration of Afatinib can be increased when it is combined with Nilotinib. |
| Nintedanib | The serum concentration of Nintedanib can be increased when it is combined with Afatinib. |
| Nitrofurantoin | Afatinib may decrease the excretion rate of Nitrofurantoin which could result in a higher serum level. |
| Norgestimate | The serum concentration of Afatinib can be increased when it is combined with Norgestimate. |
| Nortriptyline | The serum concentration of Nortriptyline can be increased when it is combined with Afatinib. |
| Novobiocin | Novobiocin may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Omadacycline | The serum concentration of Omadacycline can be increased when it is combined with Afatinib. |
| Ombitasvir | Afatinib may decrease the excretion rate of Ombitasvir which could result in a higher serum level. |
| Omeprazole | Omeprazole may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Osimertinib | The serum concentration of Osimertinib can be increased when it is combined with Afatinib. |
| Oteseconazole | The serum concentration of Afatinib can be increased when it is combined with Oteseconazole. |
| Oxaliplatin | Afatinib may decrease the excretion rate of Oxaliplatin which could result in a higher serum level. |
| Oxetacaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Oxetacaine. |
| Oxybuprocaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Oxybuprocaine. |
| Ozanimod | Afatinib may decrease the excretion rate of Ozanimod which could result in a higher serum level. |
| Pacritinib | The serum concentration of Afatinib can be increased when it is combined with Pacritinib. |
| Palbociclib | The serum concentration of Afatinib can be increased when it is combined with Palbociclib. |
| Paliperidone | The serum concentration of Afatinib can be increased when it is combined with Paliperidone. |
| Panobinostat | The serum concentration of Panobinostat can be increased when it is combined with Afatinib. |
| Pantoprazole | Pantoprazole may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Parathyroid | The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Afatinib. |
| Paritaprevir | Paritaprevir may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Pazopanib | The serum concentration of Pazopanib can be increased when it is combined with Afatinib. |
| Peginesatide | The risk or severity of Thrombosis can be increased when Peginesatide is combined with Afatinib. |
| Phenol | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Phenol. |
| Pibrentasvir | The serum concentration of Afatinib can be increased when it is combined with Pibrentasvir. |
| Pitavastatin | Afatinib may decrease the excretion rate of Pitavastatin which could result in a higher serum level. |
| Pitolisant | The serum concentration of Afatinib can be increased when it is combined with Pitolisant. |
| Pomalidomide | The serum concentration of Pomalidomide can be increased when it is combined with Afatinib. |
| Ponatinib | The serum concentration of Afatinib can be increased when it is combined with Ponatinib. |
| Posaconazole | The serum concentration of Posaconazole can be increased when it is combined with Afatinib. |
| Potassium Iodide | The therapeutic efficacy of Potassium Iodide can be decreased when used in combination with Afatinib. |
| Potassium | The therapeutic efficacy of Potassium perchlorate can be decreased when used in combination with Afatinib. |
| Pralatrexate | Afatinib may decrease the excretion rate of Pralatrexate which could result in a higher serum level. |
| Pralsetinib | The serum concentration of Pralsetinib can be increased when it is combined with Afatinib. |
| Pramocaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Pramocaine. |
| Pravastatin | Pravastatin may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Prazosin | Afatinib may decrease the excretion rate of Prazosin which could result in a higher serum level. |
| Prednisolone | The serum concentration of Afatinib can be decreased when it is combined with Prednisolone phosphate. |
| Prilocaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Prilocaine. |
| Procaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Procaine. |
| Progesterone | Progesterone may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Propafenone | The serum concentration of Afatinib can be increased when it is combined with Propafenone. |
| Proparacaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Proparacaine. |
| Propoxycaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Propoxycaine. |
| Propylthiouracil | The therapeutic efficacy of Propylthiouracil can be decreased when used in combination with Afatinib. |
| Protirelin | The therapeutic efficacy of Protirelin can be decreased when used in combination with Afatinib. |
| Prucalopride | The serum concentration of Prucalopride can be increased when it is combined with Afatinib. |
| Quinidine | The serum concentration of Afatinib can be increased when it is combined with Quinidine. |
| Quinine | The serum concentration of Afatinib can be increased when it is combined with Quinine. |
| Rabeprazole | Rabeprazole may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Raloxifene | Afatinib may decrease the excretion rate of Raloxifene which could result in a higher serum level. |
| Ranolazine | The serum concentration of Ranolazine can be increased when it is combined with Afatinib. |
| Regorafenib | The serum concentration of Afatinib can be increased when it is combined with Regorafenib. |
| Relugolix | The serum concentration of Relugolix can be increased when it is combined with Afatinib. |
| Reserpine | The serum concentration of Afatinib can be increased when it is combined with Reserpine. |
| Revefenacin | Afatinib may decrease the excretion rate of Revefenacin which could result in a higher serum level. |
| Rifampicin | The serum concentration of Afatinib can be decreased when it is combined with Rifampicin. |
| Rifamycin | The serum concentration of Afatinib can be increased when it is combined with Rifamycin. |
| Rifaximin | The serum concentration of Rifaximin can be increased when it is combined with Afatinib. |
| Rilpivirine | Rilpivirine may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Riluzole | Afatinib may decrease the excretion rate of Riluzole which could result in a higher serum level. |
| Rimegepant | The serum concentration of Rimegepant can be increased when it is combined with Afatinib. |
| Riociguat | Afatinib may decrease the excretion rate of Riociguat which could result in a higher serum level. |
| Ripretinib | The serum concentration of Afatinib can be increased when it is combined with Ripretinib. |
| Ritonavir | The serum concentration of Afatinib can be increased when it is combined with Ritonavir. |
| Rivaroxaban | Afatinib may decrease the excretion rate of Rivaroxaban which could result in a higher serum level. |
| Rolapitant | The serum concentration of Afatinib can be increased when it is combined with Rolapitant. |
| Romidepsin | The serum concentration of Romidepsin can be increased when it is combined with Afatinib. |
| Ropivacaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Ropivacaine. |
| Rosuvastatin | Afatinib may decrease the excretion rate of Rosuvastatin which could result in a higher serum level. |
| Roxadustat | The serum concentration of Afatinib can be increased when it is combined with Roxadustat. |
| Rucaparib | Afatinib may decrease the excretion rate of Rucaparib which could result in a higher serum level. |
| Safinamide | Safinamide may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Salmon calciton | The therapeutic efficacy of Salmon calcitonin can be decreased when used in combination with Afatinib. |
| Sapropterin | The serum concentration of Afatinib can be increased when it is combined with Sapropterin. |
| Saquinavir | The serum concentration of Afatinib can be increased when it is combined with Saquinavir. |
| Sarecycline | The serum concentration of Afatinib can be increased when it is combined with Sarecycline. |
| Selexipag | The serum concentration of Selexipag can be increased when it is combined with Afatinib. |
| Selumetinib | Afatinib may decrease the excretion rate of Selumetinib which could result in a higher serum level. |
| Sildenafil | The serum concentration of Afatinib can be increased when it is combined with Sildenafil. |
| Silodosin | The excretion of Silodosin can be decreased when combined with Afatinib. |
| Simeprevir | The serum concentration of Afatinib can be increased when it is combined with Simeprevir. |
| Simvastatin | The serum concentration of Afatinib can be increased when it is combined with Simvastatin. |
| Sirolimus | The serum concentration of Sirolimus can be increased when it is combined with Afatinib. |
| Sitagliptin | The serum concentration of Sitagliptin can be increased when it is combined with Afatinib. |
| Sofosbuvir | Afatinib may decrease the excretion rate of Sofosbuvir which could result in a higher serum level. |
| Sorafenib | The serum concentration of Afatinib can be increased when it is combined with Sorafenib. |
| Sotagliflozin | The serum concentration of Afatinib can be increased when it is combined with Sotagliflozin. |
| Sotorasib | The serum concentration of Afatinib can be increased when it is combined with Sotorasib. |
| St. John’s Wort | The serum concentration of Afatinib can be decreased when it is combined with St. John’s Wort. |
| Stiripentol | The excretion of Afatinib can be decreased when combined with Stiripentol. |
| Sulfasalazine | Sulfasalazine may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Sumatriptan | Afatinib may decrease the excretion rate of Sumatriptan which could result in a higher serum level. |
| Sunitinib | Sunitinib may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Suvorexant | The serum concentration of Afatinib can be increased when it is combined with Suvorexant. |
| Tacrolimus | The serum concentration of Afatinib can be increased when it is combined with Tacrolimus. |
| Tafamidis | The serum concentration of Afatinib can be increased when it is combined with Tafamidis. |
| Talazoparib | The serum concentration of Talazoparib can be increased when it is combined with Afatinib. |
| Tamoxifen | The serum concentration of Afatinib can be increased when it is combined with Tamoxifen. |
| Taurocholic acid | Taurocholic acid may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Tazemetostat | Afatinib may decrease the excretion rate of Tazemetostat which could result in a higher serum level. |
| Technetium | The serum concentration of Technetium Tc-99m sestamibi can be increased when it is combined with Afatinib. |
| Tegaserod | Afatinib may decrease the excretion rate of Tegaserod which could result in a higher serum level. |
| Telaprevir | The serum concentration of Afatinib can be increased when it is combined with Telaprevir. |
| Telmisartan | Telmisartan may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Temsirolimus | The serum concentration of Afatinib can be increased when it is combined with Temsirolimus. |
| Teniposide | Afatinib may decrease the excretion rate of Teniposide which could result in a higher serum level. |
| Tenofovir | The serum concentration of Tenofovir alafenamide can be increased when it is combined with Afatinib. |
| Tenofovir | The serum concentration of Tenofovir disoproxil can be increased when it is combined with Afatinib. |
| Tepotinib | The serum concentration of Tepotinib can be increased when it is combined with Afatinib. |
| Teriflunomide | Teriflunomide may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Teriparatide | The therapeutic efficacy of Teriparatide can be decreased when used in combination with Afatinib. |
| Testosterone | Afatinib may decrease the excretion rate of Testosterone which could result in a higher serum level. |
| Testosterone | Afatinib may decrease the excretion rate of Testosterone cypionate which could result in a higher serum level. |
| Testosterone | Afatinib may decrease the excretion rate of Testosterone enanthate which could result in a higher serum level. |
| Tetracaine | The risk or severity of methemoglobinemia can be increased when Afatinib is combined with Tetracaine. |
| Tezacaftor | The serum concentration of Tezacaftor can be increased when it is combined with Afatinib. |
| Thyroid, porcine | The therapeutic efficacy of Thyroid, porcine can be decreased when used in combination with Afatinib. |
| Thyrotropin alfa | The therapeutic efficacy of Thyrotropin alfa can be decreased when used in combination with Afatinib. |
| Ticagrelor | The serum concentration of Afatinib can be increased when it is combined with Ticagrelor. |
| Tipranavir | The serum concentration of Afatinib can be increased when it is combined with Tipranavir. |
| Tivozanib | Tivozanib may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Tolvaptan | The serum concentration of Tolvaptan can be increased when it is combined with Afatinib. |
| Topotecan | The serum concentration of Topotecan can be increased when it is combined with Afatinib. |
| Toremifene | The serum concentration of Afatinib can be increased when it is combined with Toremifene. |
| Trastuzumab | The serum concentration of Trastuzumab emtansine can be increased when it is combined with Afatinib. |
| Trazodone | The serum concentration of Afatinib can be decreased when it is combined with Trazodone. |
| Trilaciclib | Afatinib may decrease the excretion rate of Trilaciclib which could result in a higher serum level. |
| Trimipramine | The serum concentration of Trimipramine can be increased when it is combined with Afatinib. |
| Tucatinib | Tucatinib may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Ubrogepant | The serum concentration of Ubrogepant can be increased when it is combined with Afatinib. |
| Umbralisib | The serum concentration of Afatinib can be increased when it is combined with Umbralisib. |
| Umeclidinium | The serum concentration of Umeclidinium can be increased when it is combined with Afatinib. |
| Vandetanib | The serum concentration of Afatinib can be increased when it is combined with Vandetanib. |
| Vardenafil | The serum concentration of Afatinib can be increased when it is combined with Vardenafil. |
| Velpatasvir | The serum concentration of Afatinib can be increased when it is combined with Velpatasvir. |
| Vemurafenib | The serum concentration of Afatinib can be increased when it is combined with Vemurafenib. |
| Venetoclax | The serum concentration of Afatinib can be increased when it is combined with Venetoclax. |
| Venlafaxine | Venlafaxine may increase the excretion rate of Afatinib which could result in a lower serum level and potentially a reduction in efficacy. |
| Verapamil | The serum concentration of Afatinib can be increased when it is combined with Verapamil. |
| Vinblastine | The serum concentration of Vinblastine can be increased when it is combined with Afatinib. |
| Vincristine | The excretion of Vincristine can be decreased when combined with Afatinib. |
| Vinflunine | The serum concentration of Vinflunine can be increased when it is combined with Afatinib. |
| Vismodegib | Vismodegib may decrease the excretion rate of Afatinib which could result in a higher serum level. |
| Voclosporin | The serum concentration of Afatinib can be increased when it is combined with Voclosporin. |
| Vorapaxar | The serum concentration of Afatinib can be increased when it is combined with Vorapaxar. |
| Voriconazole | The serum concentration of Afatinib can be increased when it is combined with Voriconazole. |
| Voxilaprevir | The serum concentration of Afatinib can be increased when it is combined with Voxilaprevir. |
| Zidovudine | Afatinib may decrease the excretion rate of Zidovudine which could result in a higher serum level. |
| Zonisamide | The serum concentration of Afatinib can be increased when it is combined with Zonisamide. |
Pregnancy and Lactation
US FDA pregnancy category: Not assigned.
Pregnancy
Based on findings from animal studies and its mechanism of action, GILOTRIF can cause fetal harm when administered to a pregnant woman. There are no available data on the use of GILOTRIF in pregnant women. Administration of afatinib to pregnant rabbits during organogenesis at exposures approximately 0.2 times the exposure in humans at the recommended dose of 40 mg daily resulted in embryotoxicity and, in rabbits showing maternal toxicity, increased abortions at late gestational stages [see Data]. Advise a pregnant woman of the
potential risk to a fetus.
Lactation
No information is available on the clinical use of afatinib during breastfeeding. Because afatinib is about 95% bound to plasma proteins, the amount in milk is likely to be low. However, its half-life is about 37 hours and it might accumulate in the infant. the manufacturer recommends that breastfeeding be discontinued during afatinib therapy and for 2 weeks after the last dose.
How should this medicine be used?
Afatinib comes as a tablet to take by mouth. It is usually taken on an empty stomach once a day, at least 1 hour before or 2 hours after eating a meal or snack. Take afatinib at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take afatinib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Your doctor may temporarily or permanently stop your treatment or decrease the dose if you experience serious side effects of afatinib. Talk to your doctor about how you are feeling during your treatment. Continue to take afatinib even if you feel well. Do not stop taking afatinib without talking to your doctor. Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient.
What special precautions should I follow?
Before taking afatinib,
- tell your doctor and pharmacist if you are allergic to afatinib, any other medications, or any of the ingredients in afatinib tablets. Ask your pharmacist for a list of the ingredients.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: amiodarone (Cordarone, Pacerone); certain antifungal medications such as itraconazole (Sporanox) and ketoconazole (Nizoral); cyclosporine (Gengraf, Neoral, Sandimmune); erythromycin (E.E.S., Erythrocin, others); certain medications for human immunodeficiency virus (HIV) such as nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Invirase); certain medications for seizures such as carbamazepine (Carbatrol, Equetro, Tegretol), phenobarbital, and phenytoin (Dilantin); quinidine (in Nuedexta); rifampin (Rimactane, Rifadin, in Rifater); tacrolimus (Prograf); and verapamil (Calan, Covera, Isoptin, Verelan). Many other medications may also interact with afatinib, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor what herbal products you are taking, especially St. John’s wort.
- tell your doctor if you are of Asian descent or have or have ever had lung or breathing problems (other than lung cancer); eye problems, including dry eyes; heart problems; liver or kidney disease; or any other medical condition. Also, tell your doctor if you wear contact lenses.
- tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while you are taking afatinib and for at least 2 weeks after your treatment. Talk to your doctor about birth control methods that you can use during your treatment. If you become pregnant while taking afatinib, call your doctor immediately. Afatinib may harm the fetus.
- tell your doctor if you are breastfeeding. You should not breastfeed while you are taking afatinib.
- plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Afatinib may make your skin sensitive to sunlight. Exposure to sunlight increases the risk that you will develop a rash or acne during your treatment with afatinib.
Monitoring
Afatinib has several monitoring requirements.[rx][rx] These include:
- Given that dermatology adverse reactions are the most commonly reported adverse reactions during treatment, patients should be advised to avoid sun exposure if possible or utilize adequate sun protection.[rx]
- Monitor for signs and symptoms of volume depletion in patients with diarrhea
- Hepatic impairment was commonly observed in clinical trials; it is advised to monitor liver function periodically during treatment.
- The patient’s renal function requires periodic monitoring.
- Keratitis is one of the rare adverse effects but reported in clinical trials – therapy should be interrupted with any suspected keratitis.
- Recommended to reduce the dose in case of paronychia
- Monitor patients for any signs and symptoms that raise concern for pulmonary toxicity – interstitial lung disease occurred in a small percentage of patients.
- Assess left ventricle function before and during treatment in high-risk cardiac patients. This drug should be used with caution in patients with cardiac risk factors and/or decreased left ventricle heart failure as patients with significant cardiac history met exclusion criteria for clinical trials.
Takahashi T. et al. studied using afatinib trough plasma concentrations in patients with non-small-cell lung cancer to improve the safety and efficacy of afatinib therapy.[rx]
References
