Gefitinib is an oral medication taken as a tablet. It is crucial to follow the prescribed dosage and administration instructions carefully.
- Dosage: The standard recommended dose of gefitinib is 250 mg orally once daily.
- Administration:
- The tablet can be taken with or without food, but it should be taken at approximately the same time each day.
- Swallow the tablet whole with water.
- For patients with difficulty swallowing: The tablet can be dispersed in a glass of non-carbonated drinking water (4 to 8 ounces). The tablet should be dropped into the water without crushing it, and the glass should be swirled occasionally until the tablet is completely dispersed (this may take up to 20 minutes). The dispersion should be drunk immediately (within 60 minutes) after it is complete. The container should then be rinsed with more water and the rinse also consumed. This method can also be used for administration via a nasogastric tube.
- Missed Dose: If a dose is missed, it should be taken as soon as the patient remembers, unless the next dose is due within 12 hours. In that case, the missed dose should be skipped, and the regular dosing schedule resumed. Do not take a double dose to make up for a missed dose.
- Duration of Treatment: Treatment with gefitinib is typically continued until disease progression or until unacceptable toxicity occurs.
- Dose Modifications: The healthcare provider may interrupt or discontinue treatment based on the severity of adverse reactions (e.g., severe skin rash, diarrhea, or liver enzyme elevations). Dose reductions are generally not recommended; instead, treatment interruption is preferred for managing toxicities.
Gefitinib functions as a highly selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The EGFR is a protein found on the surface of many normal cells, but it is often overexpressed or mutated in cancer cells. When activated, EGFR plays a critical role in cell growth, proliferation, survival, and angiogenesis (formation of new blood vessels).
In certain NSCLC tumors, specific mutations in the EGFR gene (such as exon 19 deletions or L858R point mutations) lead to a constitutively active EGFR protein. This means the receptor is constantly “on,” sending continuous signals that promote uncontrolled cancer cell division and survival.
Gefitinib works by:
- Competitive Inhibition: It competitively binds to the ATP (adenosine triphosphate) binding site within the tyrosine kinase domain of the mutated EGFR. ATP is the energy source required for EGFR to signal.
- Blocking Downstream Signaling: By inhibiting ATP binding, gefitinib prevents the autophosphorylation of EGFR and subsequently blocks the activation of downstream signaling pathways (e.g., RAS/MAPK, PI3K/Akt, and STAT pathways) that are critical for cancer cell growth and survival.
- Inducing Apoptosis: This inhibition ultimately leads to the arrest of cell proliferation and the induction of apoptosis (programmed cell death) in cancer cells that are dependent on the mutated EGFR for their growth.
This targeted approach helps to selectively inhibit cancer cells while minimizing damage to healthy cells, leading to a more favorable side effect profile compared to conventional chemotherapy.
While gefitinib is a targeted therapy, it can still cause various side effects, some of which can be serious. Patients require close monitoring during treatment.
- Very Common Side Effects (≥10%):
- Skin reactions: Acne-like rash (often on the face, neck, chest, back), dry skin, itchy skin, paronychia (nail bed inflammation).
- Diarrhea: Can range from mild to severe, and may lead to dehydration.
- Nausea and Vomiting: Usually mild.
- Anorexia/Decreased Appetite: Can lead to weight loss.
- Asthenia (weakness/fatigue).
- Elevated Liver Enzymes: Increases in AST and ALT (liver function tests).
- Common Side Effects (1% to <10%):
- Stomatitis (sore mouth), dry mouth.
- Conjunctivitis (eye irritation), dry eyes, blepharitis (eyelid inflammation).
- Nail disorders.
- Alopecia (hair loss).
- Hemorrhage (e.g., epistaxis/nosebleeds, hematuria/blood in urine).
- Fever.
- Proteinuria (protein in urine).
- Cystitis (bladder inflammation).
- Uncommon to Rare but Serious Side Effects (<1%):
- Interstitial Lung Disease (ILD): This is a severe and potentially fatal inflammatory lung condition. Symptoms include new or worsening shortness of breath, cough, and fever. Immediate medical attention is required.
- Hepatotoxicity: Severe liver problems, including hepatitis and rare cases of fatal hepatic failure. Regular liver function monitoring is crucial.
- Gastrointestinal Perforation: A rare but life-threatening complication, indicated by severe abdominal pain.
- Bullous Skin Conditions: Severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), or erythema multiforme, characterized by blistering, peeling skin, and flu-like symptoms.
- Ocular disorders: Including corneal erosion or ulcerative keratitis.
Patients should report any new or worsening symptoms to their healthcare provider immediately.
Gefitinib carries several important warnings and precautions due to the potential for serious adverse reactions. Close monitoring by a healthcare provider is essential throughout treatment.
- Interstitial Lung Disease (ILD): This is a serious and potentially fatal adverse reaction. Patients experiencing new or worsening respiratory symptoms (dyspnea, cough, fever) should immediately contact their doctor. Gefitinib should be interrupted and ILD promptly investigated. If ILD is confirmed, gefitinib should be permanently discontinued.
- Hepatotoxicity: Liver function abnormalities, including severe hepatitis and rare cases of fatal hepatic failure, have been reported. Regular monitoring of liver function tests (ALT, AST, bilirubin) is recommended. Gefitinib may need to be withheld or discontinued if liver test abnormalities are severe or worsen.
- Severe Diarrhea and Dehydration: Diarrhea is a very common side effect and can be severe, leading to dehydration and electrolyte imbalance. Patients should be advised on management strategies and contact their doctor if diarrhea is severe or persistent.
- Skin Reactions: Severe and widespread skin reactions (including bullous conditions like SJS/TEN) can occur. Patients should monitor for skin changes and seek immediate medical attention for blistering, peeling, or widespread rash.
- Ocular Disorders: Eye problems like keratitis (corneal inflammation) and corneal erosion have been reported. Patients experiencing eye pain, redness, blurred vision, or light sensitivity should be evaluated by an ophthalmologist.
- Gastrointestinal Perforation: Though rare, this life-threatening complication can occur. Patients presenting with severe, acute abdominal pain should be promptly evaluated.
- Embryo-Fetal Toxicity: Gefitinib can cause fetal harm when administered to pregnant women. Females of reproductive potential must be advised to use effective contraception during treatment and for at least 1 month after the last dose.
Gefitinib is primarily metabolized by the cytochrome P450 enzyme CYP3A4 in the liver, and to a lesser extent by CYP2D6. This metabolic pathway makes it susceptible to interactions with numerous other medications.
- CYP3A4 Inducers: Strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, St. John’s wort) can significantly decrease the plasma concentrations of gefitinib, potentially reducing its efficacy. In some cases, a higher dose of gefitinib (e.g., 500 mg daily) might be considered if a strong CYP3A4 inducer cannot be avoided, followed by a return to 250 mg daily upon discontinuation of the inducer.
- CYP3A4 Inhibitors: Strong or moderate CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, grapefruit juice) can increase gefitinib exposure, potentially leading to increased side effects. Close monitoring for adverse reactions is necessary.
- Gastric pH-Elevating Agents: Medications that significantly and persistently increase gastric pH (e.g., proton pump inhibitors like omeprazole, H2-receptor antagonists like ranitidine) can reduce the solubility and absorption of gefitinib, thereby decreasing its plasma concentrations and potentially reducing its efficacy. Concomitant use with PPIs should generally be avoided. If an H2-receptor antagonist is required, it should be taken approximately 10 hours before or 2 hours after the gefitinib dose. Antacids should also be used cautiously and ideally spaced from gefitinib administration.
- Warfarin: Co-administration with warfarin (an anticoagulant) can increase the international normalized ratio (INR) and prothrombin time (PT), increasing the risk of bleeding. Close monitoring of INR/PT is recommended.
Patients should inform their healthcare provider about all prescription, over-the-counter medications, herbal supplements, and dietary changes to manage potential drug interactions effectively.
The standard dosage of Gefitinib is straightforward, but adherence to specific administration instructions and any dose modifications for toxicity is crucial.
- Recommended Dose: The recommended dose for adult patients is 250 mg orally once daily.
- Administration: Gefitinib tablets can be taken with or without food. It is best to take it at approximately the same time each day to maintain consistent drug levels.
- For Patients with Swallowing Difficulty: The 250 mg tablet can be dispersed in half a glass (4 to 8 ounces) of non-carbonated water. The tablet should be dropped into the water (without crushing) and swirled occasionally for about 15-20 minutes until it disperses. The dispersion must be drunk immediately (within 60 minutes). The glass should then be rinsed with another 4 to 8 ounces of water, and the rinse should also be consumed. This method can also be used for administration via a nasogastric tube.
- Missed Dose: If a patient misses a dose, they should take it as soon as they remember, unless it is less than 12 hours before the next scheduled dose. In that case, the missed dose should be skipped, and the regular schedule resumed. Do not double dose.
- Dose Modifications for Adverse Reactions: Dose reductions are generally not recommended for gefitinib. Instead, management of adverse reactions typically involves temporary dose interruptions (e.g., for up to 14 days) or permanent discontinuation, depending on the severity and persistence of the toxicity.
Gefitinib is a prescription-only medication. It is not available over-the-counter.
- Specialist Prescription: Gefitinib must be prescribed by a physician who is experienced in the use of anticancer therapies and knowledgeable about the treatment of non-small cell lung cancer.
- Diagnostic Testing: Prior to initiating treatment, patients must undergo an FDA-approved diagnostic test to confirm the presence of specific EGFR activating mutations (e.g., exon 19 deletions or L858R substitution) in their tumor. This diagnostic requirement ensures that the therapy is targeted to patients who are most likely to benefit.
- Close Monitoring: Due to the potential for serious side effects, patients receiving gefitinib require close medical supervision, including regular monitoring of liver function tests, kidney function, and assessment for pulmonary and dermatological toxicities.
- Patient Education: Healthcare providers are responsible for educating patients about potential side effects, especially serious ones like ILD and severe skin reactions, and instructing them on when to seek immediate medical attention.
Patients should never attempt to obtain or use gefitinib without a valid prescription and ongoing medical oversight.
