Description

Simple

A chemotherapy medication used to treat a certain type of lung cancer with a specific genetic mutation.

Clinical

A tyrosine kinase inhibitor used as first-line therapy to treat non-small cell lung carcinoma (NSCLC) that meets certain genetic mutation criteria.

Overview

Gefitinib (originally coded ZD1839) is a drug used in the treatment of certain types of cancer. Acting in a similar manner to erlotinib (marketed as Tarceva), gefitinib selectively targets the mutant proteins in malignant cells. It is marketed by AstraZeneca under the trade name Iressa.

Pharmacology

Indication

For the continued treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of either platinum-based or docetaxel chemotherapies.

Pharmacodynamic

Gefitinib inhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including the tyrosine kinases associated with the epidermal growth factor receptor (EGFR-TK). EGFR is expressed on the cell surface of many normal cells and cancer... Read more

Mechanism of action

Gefitinib is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase that binds to the adenosine triphosphate (ATP)-binding site of the enzyme. EGFR is often shown to be overexpressed in certain human carcinoma cells, such as lung and breast cancer cells. Overexpression leads to... Read more

Absorption

Absorbed slowly after oral administration with a mean bioavailability of 60%. Peak plasma levels occurs 3-7 hours post-administration. Food does not affect the bioavailability of gefitinib.

Protein binding

90% primarily to serum albumin and alpha 1-acid glycoproteins (independent of drug concentrations).

Volume of distribution

1400 L [IV administration]

Clearance

595 mL/min [IV administration]

Half life

48 hours [IV administration]

Route of elimination

Elimination is by metabolism (primarily CYP3A4) and excretion in feces. Excretion is predominantly via the feces (86%), with renal elimination of drug and metabolites accounting for less than 4% of the administered dose.

Toxicity

The acute toxicity of gefitinib up to 500 mg in clinical studies has been low. In non-clinical studies, a single dose of 12,000 mg/m2 (about 80 times the recommended clinical dose on a mg/m2 basis) was lethal to rats. Half this dose caused no mortality in mice. Symptoms of over... Read more

Adverse Effects

Contraindications

Information currently not available.

Food Interactions

  • Avoid grapefruit products.
  • Take with or without food. The absorption is unaffected by food.

Interactions

Type in a drug name to check for interaction with Gefitinib
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
Gefitinib may increase the anticoagulant activities of (R)-warfarin.
(S)-Warfarin
Gefitinib may increase the anticoagulant activities of (S)-Warfarin.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Gefitinib can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
3,5-diiodothyropropionic acid
The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Gefitinib.
3,5-Diiodotyrosine
The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Gefitinib.
4-hydroxycoumarin
Gefitinib may increase the anticoagulant activities of 4-hydroxycoumarin.
4-Methoxyamphetamine
The metabolism of 4-Methoxyamphetamine can be decreased when combined with Gefitinib.
5-methoxy-N,N-dimethyltryptamine
The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Gefitinib.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be decreased when combined with Gefitinib.
Abaloparatide
The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Gefitinib.
Abatacept
The metabolism of Gefitinib can be increased when combined with Abatacept.
Abemaciclib
Gefitinib may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
Abiraterone
The metabolism of Gefitinib can be decreased when combined with Abiraterone.
Acalabrutinib
The metabolism of Gefitinib can be decreased when combined with Acalabrutinib.
Acebutolol
The metabolism of Gefitinib can be decreased when combined with Acebutolol.
Acenocoumarol
Gefitinib may increase the anticoagulant activities of Acenocoumarol.
Acetaminophen
The serum concentration of Acetaminophen can be increased when it is combined with Gefitinib.
Acetohexamide
The metabolism of Acetohexamide can be decreased when combined with Gefitinib.
Acetylsalicylic acid
The metabolism of Acetylsalicylic acid can be decreased when combined with Gefitinib.
Adalimumab
The metabolism of Gefitinib can be increased when combined with Adalimumab.
2 References
  1. 1 . Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, Mardis E, Kupfer D, Wilson R, Kris M, Varmus H: EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13306-11. Epub 2004 Aug 25.PubMed: 15329413
  2. 2 . Sordella R, Bell DW, Haber DA, Settleman J: Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science. 2004 Aug 20;305(5687):1163-7. Epub 2004 Jul 29.PubMed: 15284455