Geftinat tablets are categorized as kinase inhibitor, which exhibits anti-cancer activity by undergoing mechanism like protein kinase inhibition. Geftinat contains an active compound known as Gefitinib which is chemically known as anilinoquinazoline which contains anti-neoplastic effects. Geftinat is a FDA approved product, manufactured by Natco pharma.
Geftinat indication and usage
Geftinat is considered as first line therapy in non-small cell lung carcinoma in metastatic stage, tumor cell containing epidermal growth factor receptors like exon 19 deletion or exon 21 substitution mutations which is identified by FDA approved test.
Geftinat pharmacological action
Cancer cells expressed epidermal growth factor receptors on their cell surface, occurred in both healthy and cancer infected cells.
These receptors involved in development of cell growth and multiplication. Some epidermal growth factor receptors have stimulating mutations (changes) within non small cell lung cancer cells which are providing encouragement to cancer cell growth, blockade of apoptosis occurs, which may elevates angiogenic factors and promoting metastasis process.
Geftinat containing Gefitinib causes unstable inhibition of tyrosine kinase and triggering variation of EGFR, hindering the autophosphorylation of tyrosine debris related with receptor, through prohibits following signaling and blockade EGFR dependent multiplication
Geftinat undergoing ADME
The mean bioavailability of Gefitinib is 60%
The peak plasma concentration time of Gefitinib is reaches within 3 to 7 hours after drug intake
Gefitinib is distributed throughout the body and causes steady state volume of distribution in 1400L
The human plasma protein bound of Gefitinib is occurs as 90%.
The metabolism of Gefitinib is occurs through hepatically, by using CYP3A4
In metabolism of Gefitinib includes three sections of biotransformation as:
1. Metabolism of N-propoxymorpholino group
2. Methoxy substituent on quinazoline demethylation occur
3. Halogenated phenyl group undergoes oxidative defluorination
The major active metabolite of Gefitinib is O desmethyl Gefitinib which is formed by CYP2D6 metabolism. Gefitinib is cleared away with the help of liver, with half life elimination occurring within 48 hours. The steady state plasma concentration is accomplished within 10 days after daily single dose. The elimination of Gefitinib is occurs through feces with the range of 86% and renal elimination also occurred with less than 4%.
Geftinat dosage and administration
The usual prescribed dosage of Geftinat tablets are 250mg should be given orally as a single dose by administering with or without food continuously. If patient feel difficult for swallow the tablets, must immerse the tablets with 4 to 8 ounces of water and mix it well for relatively 15 minutes. Take the solution immediately through naso-gastric tube.
Refuse the Geftinat tablets, if patients have any of the following conditions such as; Acute outbreak or aggravation of pulmonary symptoms like cough, fever, dyspnea In case of elevation of ALT & AST levels; Severe ocular disorders like keratitis High skin reactions Geftinat therapy should be discontinuing forever; in case of Gastrointestinal perforation Enduring ulcerative keratitis Serious liver damage Interstitial lung disease
Strong CYP3A4 inducers
In the absence of adverse effects, the dosage is increased to 500mg; continue the Geftinat therapy with 250mg after cessation of strong CYP3A4 inducers
The major adverse effect of Geftinat tablets occurs as
Liver toxicity Gastrointestinal perforation, Severe diarrhea, Bullous &exfoliative skin disorders, Ocular disorders, Interstitial lung disease
The most common side effects are
Headache, Diarrhea, Fatigue Respiratory failure occurs due to pneumonia & pulmonary embolism, Nausea, Vomiting, Skin reactions, Nail disorders, Stomatitis, Loss of appetite, Conjunctivitis, Blepharitis, Dry eye, Mucosal inflammation, tongue ulceration, eye irritation, eyelid Pruritus, edema, Elevation of AST, ALT, Proteinuria, Hemorrhagic cystitis, Cutaneous vasculitis
Interstitial lung disease
In this case, Geftinat therapy is discontinue and rapidly examine for ILD in any patients who have acute respiratory problems.
Patient receiving Geftinat tablets have a chance to elevate AST & ALT levels and increased bilirubin levels cause hepatotoxicity and to recover from this condition discontinue the therapy.
For this condition, stop the therapy permanently.
Discontinue the therapy with Geftinat
Ocular disorders like corneal erosion, aberrant eyelash growth may occur during the therapy of Geftinat , discontinue the Geftinat therapy.
It includes Stevens Johnson’s syndrome, epidermal necrolysis & Erythema multiforme formed during the therapy. In this case, Geftinat therapy should be postponed or discontinued.
Embryo fetal toxicity
Gefitinib causes fetal harm, like fetotoxicity and neonatal death. Avoid this therapy in pregnant women and use effective contraception methods.
Strong CYP3A4 inducers
In combination with Geftinat tablets causes increasing the metabolism of Gefitinib and reducing the plasma concentration of Gefitinib. In this condition the dosage of Geftinat is increased to 500mg and followed by 250mg for 7 days after stopping the CYP3A4 inducers like phenytoin, rifampicin or tricyclic anti-depressants.
Strong CYP3A4 inhibitors
Concurrent use with Geftinat tablets leads to cause decreasing the metabolism of Gefitinib and increasing the plasma concentration of Gefitinib. Avoid this concomitant otherwise monitor the patients frequently who are receiving this combinational therapy.
Drugs increasing gastric pH
Co administration of Geftinat tablets with proton pump inhibitors, antacids or histamine H2 receptor antagonist may leads to decrease the plasma concentration of Gefitinib. Geftinat tablets are administered 12 hours after the last dose or 12 hours before the dose of proton pump inhibitors; Geftinat should be taken 6 hours after or before the dose of H2 receptor antagonist or antacids. While taking warfarin in Geftinat therapy causes increased risk of hemorrhage. To avoid this life threatening condition, patient should be monitored periodically for alteration in prothrombin time.