Version May 2024
Note: Select patients for treatment based on presence of epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations in tumor or plasma specimen (if mutation is not detected in plasma, test tumor tissue, if feasible).
Non–small cell lung cancer, metastatic, with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations: Oral: 250 mg once daily until disease progression or unacceptable toxicity.
Missed doses: Do not take a missed dose if it is within 12 hours of the next scheduled dose (skip the missed dose).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; however, gefitinib undergoes minimal renal excretion (<4% of gefitinib and metabolites). Gefitinib has not been studied in patients with CrCl ≤20 mL/minute. No need for dosage adjustment is expected (Ref).
Hemodialysis: No need for dosage adjustment is expected (Ref).
Dosage adjustment for hepatic impairment at treatment initiation:
There are no dosage adjustments provided in the manufacturer’s labeling; systemic exposure is increased in hepatic impairment; monitor for adverse reactions in patients with moderate or severe impairment.
Child-Pugh class A or patients with impairment due to hepatic metastasis: No dosage adjustment necessary (Ref).
Child-Pugh class B or C: Reduce gefitinib dose by 50% (Ref).
Dosage adjustment for hepatotoxicity during treatment:
ALT and/or AST elevations (grade 2 or higher): Withhold gefitinib for up to 14 days; may resume when fully resolved or improved to grade 1.
Severe hepatic impairment: Permanently discontinue gefitinib.
Dermatologic toxicity:
Skin reactions (grade 3 or higher): Withhold gefitinib for up to 14 days; may resume when fully resolved or improved to grade 1.
Severe bullous, blistering or exfoliating dermatologic conditions: Interrupt or discontinue gefitinib treatment.
Gastrointestinal toxicity:
Diarrhea (grade 3 or higher): Withhold gefitinib for up to 14 days; may resume when fully resolved or improved to grade 1.
Gastrointestinal perforation: Permanently discontinue gefitinib.
Ocular toxicity:
Signs/symptoms of severe or worsening disorders, including keratitis: Withhold gefitinib for up to 14 days; may resume when fully resolved or improved to grade 1.
Persistent ulcerative keratitis: Permanently discontinue gefitinib.
Pulmonary toxicity:
Acute onset or worsening symptoms (dyspnea, cough, fever): Withhold gefitinib for up to 14 days (promptly assess for interstitial lung disease); may resume when fully resolved or improved to grade 1.
Interstitial lung disease, confirmed: Permanently discontinue gefitinib.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Dermatologic reaction (47%)
Gastrointestinal: Decreased appetite (17%), diarrhea (29%; severe diarrhea: 3%), nausea (18%), vomiting (14%)
Genitourinary: Proteinuria (35%)
Hepatic: Increased serum alanine aminotransferase (11% to 38%), increased serum aspartate aminotransferase (8% to 40%)
Neuromuscular & skeletal: Asthenia (17%)
1% to 10%:
Dermatologic: Alopecia (5%), nail disease (5%), urticaria (≤1%)
Endocrine & metabolic: Dehydration (2%)
Gastrointestinal: Stomatitis (7%), xerostomia (2%)
Hematologic & oncologic: Hemorrhage (4%; including epistaxis, hematuria)
Hepatic: Increased serum bilirubin (3%)
Hypersensitivity: Angioedema (≤1%), hypersensitivity reaction (≤1%)
Ophthalmic: Blepharitis (≤6%), conjunctivitis (≤6%), dry eye syndrome (≤6%)
Renal: Increased serum creatinine (2%)
Respiratory: Acute respiratory distress syndrome (≤1%), interstitial pulmonary disease (≤1%), pneumonitis (≤1%), pulmonary fibrosis (≤1%), pulmonary infiltrates (≤1%)
Miscellaneous: Fever (9%)
<1%:
Dermatologic: Bullous dermatitis, erythema multiforme, palmar-plantar erythrodysesthesia
Gastrointestinal: Gastrointestinal perforation, pancreatitis
Ophthalmic: Abnormal eyelash growth, corneal erosion, keratitis
Postmarketing:
Cardiovascular: Hypersensitivity angiitis
Dermatologic: Bullous skin disease (including Stevens-Johnson syndrome, toxic epidermal necrolysis)
Genitourinary: Cystitis, hemorrhagic cystitis
There are no contraindications listed in the manufacturer’s US labeling.
Canadian labeling: Hypersensitivity to gefitinib or any component of the formulation.
Concerns related to adverse effects:
• Dermatologic toxicity: Skin reactions occurred in nearly one-half of patients taking gefitinib. Bullous skin disorders, including toxic epidermal necrolysis, Stevens Johnson syndrome, erythema multiforme, and dermatitis bullous have been reported.
• GI effects: Diarrhea occurs in approximately one-third of patients; grade 3 or 4 diarrhea has been observed. GI perforation has occurred (rarely).
• Hepatotoxicity: Increases in ALT, AST, and bilirubin, including grade 3 or higher toxicity have been observed. Fatal hepatotoxicity has occurred rarely.
• Ocular toxicity: Ocular disorders, including keratitis, corneal erosion, abnormal eyelash growth, conjunctivitis, blepharitis, and dry eye have been reported; some events were grade 3. Advise patients to promptly report developing eye symptoms (eg, lacrimation, blurred vision, eye pain, red eye, light sensitivity, or vision changes).
• Pulmonary toxicity: Interstitial lung disease (ILD) or ILD-like reactions (eg, acute respiratory distress syndrome, lung infiltration, pneumonitis, or pulmonary fibrosis) have occurred (rarely) with gefitinib; some cases were grade 3 or higher and some were fatal. Promptly assess any patient with worsening respiratory symptoms (dyspnea, cough, and fever).
Special populations:
• CYP2D6 poor metabolizers: Systemic exposure of gefitinib may be increased in CYP2D6 poor metabolizers.
Other warnings/precautions:
• Appropriate use: Establish epidermal growth factor receptor (EGFR) mutation status (in tumor or plasma specimen; if mutation is not detected in plasma, test tumor tissue if feasible) prior to treatment. Information on tests to detect EGFR mutations may be found at http://www.fda.gov/companiondiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Iressa: 250 mg
Generic: 250 mg
Yes
Tablets (Gefitinib Oral)
250 mg (per each): $275.73 - $295.98
Tablets (Iressa Oral)
250 mg (per each): $311.56
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Iressa: 250 mg
Generic: 250 mg
Oral: Administer with or without food.
For patients unable to swallow the tablet whole, place tablet in 120 to 240 mL water and stir for ~15 minutes; immediately drink the liquid or administer through a naso-gastric tube. Rinse the container with 120 to 240 mL water and immediately drink or administer through naso-gastric tube.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Gefitinib may cause carcinogenicity, teratogenicity, reproductive toxicity, and has a structural or toxicity profile similar to existing hazardous agents.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Non-small cell lung cancer, metastatic: First-line treatment of metastatic non-small cell lung cancer (NSCLC) in tumors with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an approved test.
Limitation of use: Safety and efficacy have not been established in patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution mutations
Gefitinib may be confused with afatinib, axitinib, crizotinib, dacomitinib, erdafitinib, erlotinib, gilteritinib, glasdegib, imatinib, SUNItinib
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of BCRP/ABCG2, CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Antacids: May decrease the serum concentration of Gefitinib. Management: Administer gefitinib at least 6 hours before or 6 hours after administration of an antacid, and closely monitor clinical response to gefitinib. Risk D: Consider therapy modification
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Gefitinib. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Gefitinib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase the gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers; resume 250 mg dose 7 days after discontinuation of the strong inducer. Carefully monitor clinical response. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Gefitinib. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Histamine H2 Receptor Antagonists: May decrease the serum concentration of Gefitinib. Management: Administer gefitinib at least 6 hours before or 6 hours after administration of a histamine H2 receptor antagonist (H2RA), and closely monitor clinical response to gefitinib. Risk D: Consider therapy modification
Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Gefitinib. Management: Avoid use of inhibitors of the proton pump (PPIs or PCABs) with gefitinib when possible. If required, administer gefitinib 12 hours after the PPI/PCAB or 12 hours before the next dose of the PPI/PCAB. Closely monitor clinical response to gefitinib. Risk D: Consider therapy modification
Vinorelbine: Gefitinib may enhance the neutropenic effect of Vinorelbine. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Gefitinib may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Grapefruit juice may increase serum gefitinib concentrations. Management: Monitor for increased effects/toxicity with concomitant use.
Patients who could become pregnant should use effective contraception during treatment and for at least 2 weeks following the last gefitinib dose.
Adverse events have been observed in animal reproduction studies. Gefitinib may cause fetal harm if administered during pregnancy.
It is not known if gefitinib is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.
Epidermal growth factor receptor (EGFR) mutation status for exon 19 deletion or exon 21 L858R mutations in tumor or plasma specimen (if mutation is not detected in plasma, test tumor tissue if feasible) prior to treatment. Monitor liver function tests (ALT, AST, bilirubin at baseline and periodically thereafter); INR or prothrombin time (with concurrent warfarin treatment). Monitor for signs/symptoms of dermatologic toxicity, diarrhea, GI perforation, ocular toxicity, and pulmonary toxicity (promptly assess worsening respiratory symptoms, such as, dyspnea, cough, and fever); monitor closely for adverse reactions in CYP2D6 poor metabolizers and patients with hepatic impairment. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]).
Gefitinib is a tyrosine kinase inhibitor (TKI) which reversibly inhibits kinase activity of wild-type and select activation mutations of epidermal growth factor receptor (EGFR). EGFR is expressed on cell surfaces of normal and cancer cells and has a role in cell growth and proliferation. Gefitinib prevents autophosphorylation of tyrosine residues associated with the EGFR receptor, which blocks downstream signaling and EGFR-dependent proliferation. Gefitinib has a higher binding affinity for EGFR exon 19 deletion and exon 21 (L858R) substitution mutation than for wild-type EGFR.
Distribution: Vdss: 1,400 L.
Protein binding: 90%, to albumin and alpha1-acid glycoprotein.
Metabolism: Hepatic (extensive), primarily via CYP3A4, as well as CYP2D6; forms metabolites.
Bioavailability: 60%.
Half-life elimination: 48 hours.
Time to peak, plasma: 3 to 7 hours.
Excretion: Feces (86%); urine (<4%).
Hepatic function impairment: When comparing patients with hepatic impairment due to cirrhosis to healthy patients, gefitinib mean systemic exposure was increased 40% in mild impairment, 263% in moderate impairment, and 166% in severe impairment; however, in a study of patients with liver metastases, patients with liver metastases and moderate impairment had similar systemic exposure compared to patients with liver metastases and normal hepatic function.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
