Trade name : Gefticip
Active component : Gefitinib
Strength : 250mg
Pack : 30 tablets in a container
Manufactured by : Cipla Ltd
Category : Anti-neoplastic drug
Gefticip tablets are categorized as kinase inhibitor, which exhibits anti-cancer activity by undergoing mechanism like protein kinase inhibition, the main ingredient which is used as Gefitinib Iressa . Gefticip contains an active compound known as Gefitinib Iressa which is chemically known as anilinoquinazoline which contains anti-neoplastic effects. Gefticip is a FDA approved product, manufactured by Natco pharma.
Gefticip 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.
The usual prescribed dosage of Gefticip 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
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. Gefticip 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
The mean bioavailability of Gefitinib is 60%
The peak plasma concentration time of Gefitinib Iressa 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 Iressa is occurs as 90%.
The metabolism of Gefitinib is occurs through hepatically, by using CYP3A4.
Three sections of biotransformation occurs in metabolism of Gefitinib includes 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 Iressa 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%.
Drug- Drug interaction causing alteration in pharmacokinetic properties: Co administration of Gefticip with strong CYP3A4 inducers like rifampicin causes reduction in mean AUC of Gefitinib Iressa by 83%. Concurrent use of Gefticip tablet with CYP3A4 inhibitor like itraconazole leads to elevation of AUC by 80%. Co administration of drugs which affecting gastric pH like ranitidine with sodium bicarbonate, which may causes decreasing the AUC by 47%. Metoprolol is a substrate of CYP2D6, increasing the exposure by 30% which is given on day 15 Gefitinib therapy with solid tumors.
WARNING AND PRECAUTIONS
Interstitial lung disease: In this case, Gefticip therapy is discontinue and rapidly examine for ILD in any patients who have acute respiratory problems. Liver toxicity: Patient receiving Gefticip tablets have a chance to elevate AST & ALT levels and increased bilirubin levels cause hepatotoxicity and to recover from this condition discontinue the therapy. Gastrointestinal perforation: For this condition, stop the therapy permanently. Persistent diarrhea: Discontinue the therapy with Gefticip Ocular disorders: Ocular disorders like corneal erosion, aberrant eyelash growth may occur during the therapy of Gefticip, discontinue the Gefticip therapy. Skin disorders: It includes Stevens Johnson’s syndrome, epidermal necrolysis & Erythema multiforme formed during the therapy. In this case, Gefticip therapy should be postponed or discontinued. Embryo fetal toxicity: Gefitinib Iressa 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 Gefticip tablets causes increasing the metabolism of Gefitinib Iressaand reducing the plasma concentration of Gefitinib. In this condition the dosage of Gefticip 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 Gefticip tablets leads to cause decreasing the metabolism of Gefitinib and increasing the plasma concentration of Gefitinib Iressa. Avoid this concomitant otherwise monitor the patients frequently who are receiving this combinational therapy.
Drugs increasing gastric pH
Co administration of Gefticip tablets with proton pump inhibitors, antacids or histamine H2 receptor antagonist may leads to decrease the plasma concentration of Gefitinib. Gefticip tablets are administered 12 hours after the last dose or 12 hours before the dose of proton pump inhibitors; Gefticip should be taken 6 hours after or before the dose of H2 receptor antagonist or antacids. While taking warfarin in Gefticip therapy causes increased risk of hemorrhage. To avoid this life threatening condition, patient should be monitored periodically for alteration in prothrombin time.
Breast feeding should not be recommended.
There is no distinct therapy for over dosage of Gefitinib, if over dosage occurs provide supportive care and monitor the patients frequently for the signs and symptoms of over dosage of Gefitinib Iressa.
MAJOR DRAWBACK OF USE
The potency of Gefitinib has been evaluated in patients with long lasting non-small cell lung carcinoma in whose tumor cells have epidermal growth factor receptor apart from exon 19 deletions or exon 21 alternative mutations.
The major adverse effect of Gefticip tablets occurs as;
Bullous & expoliative skin disorders,
Interstitial lung diseas.
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 .
The potency and effectiveness of Gefticip tablets has not been established in pediatric patients.
The storage of Gefticip tablet container should be kept at 20℃ to 25℃ (68℉ to 77℉). Protect the container from moisture, heat and light.