Erlotinib


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Locally advanced or metastatic non-small cell lung carcinoma In patients with EGFR-activating mutations: 150 mg once daily, continued until disease progression or unacceptable toxicity occurs. Locally advanced, unresectable or metastatic pancreatic cancer In combination with gemcitabine: 100 mg once daily. Continue therapy until disease progression or unacceptable toxicity occurs. Re-assess treatment within 4-8 weeks. All doses may be reduced in decrements of 50 mg if necessary. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Dosage Details
Oral
Locally advanced, unresectable or metastatic pancreatic cancer
Adult: In combination with gemcitabine: 100 mg once daily. Continue therapy until disease progression or unacceptable toxicity occurs. Re-assess treatment within 4-8 weeks. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Oral
Locally advanced non-small cell lung carcinoma, Metastatic non-small cell lung carcinoma
Adult: In patients with EGFR-activating mutations: 150 mg once daily. Continue therapy until disease progression or unacceptable toxicity occurs. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Special Patient Group
Patients taking CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, barbiturates, St. John’s wort): Increase dose in increments of 50 mg at 2-week intervals up to a Max 450 mg as tolerated.

Patients taking inhibitors of CYP3A4 (e.g. ketoconazole, voriconazole, ritonavir, saquinavir erythromycin, clarithromycin, grapefruit juice) or CYP1A2 (e.g. ciprofloxacin): Reduce dose in decrements of 50 mg if necessary.

Active cigarette smokers or patient taking CYP1A2 inducers: Increase dose in increments of 50 mg at 2-week intervals to a Max of 300 mg.

Pharmacogenomics:

Erlotinib potently inhibits the intracellular phosphorylation of EGFR leading to blockage of downstream signalling and cell death. EGFR is expressed on the cell surface of normal cells and cancer cells. The presence of activating EGFR mutations is an important factor in the use of biomarker-based treatment strategies including tyrosine kinase inhibitor (TKI) therapy. EGFR mutation testing is required prior to therapy to determine the suitability of Erlotinib as first-line treatment or maintenance for locally advanced or metastatic NSCLC.

EGFR exon 19 deletion and exon 21 L858R mutation

According to studies, exon 19 deletion and exon 21 L858R mutation constituted most of EGFR mutations. Erlotinib has high binding affinity for EGFR exon 19 deletion and exon 21 L858R mutations. The prevalence of EGFR mutations in Asians and Caucasians are approx 30% and 8%, respectively. Patients with EGFR mutation-positive advanced NSCLC have longer progression-free survival (PFS) time with erlotinib as first-line therapy compared to standard chemotherapy. Improved overall survival (OS), longer PFS and higher response rate with TKI therapy were associated in exon 19 deletion than in exon 21 L858R mutation. However, erlotinib treatment lacks prolongation of OS in both mutations. A significant association between EGFR mutation types and age or smoking status may also be considered in selecting appropriate therapy.
Renal Impairment
Severe: Not recommended.
Hepatic Impairment
Severe: Not recommended.
Administration
Should be taken on an empty stomach. Take at least 1 hr before or 2 hr after meals.
Contraindications
Lactation.
Special Precautions
Patient with history of peptic ulceration or diverticular disease; risk factors for of developing interstitial lung disease (e.g. previous radiotherapy, pre-existing parenchymal lung disease, metastatic lung disease, pulmonary infections); history of keratitis, ulcerative keratitis or severe dry eye; low expression levels of UGT1A1 or genetic glucuronidation disorders (e.g. Gilbert’s disease). Patients taking CYP3A4 and CY1A2 inducers or inhibitors. Cigarette smokers. Renal and hepatic impairment. Pregnancy.
Adverse Reactions
Significant: Diarrhoea, renal insufficiency, keratoconjunctivitis sicca, conjunctivitis, decreased tear production, abnormal eyelash growth. Rarely, corneal perforation or ulceration, hypokalaemia microangiopathic haemolytic anaemia with thrombocytopenia.
Eye disorders: Uveitis.
Gastrointestinal disorders: Nausea, vomiting, stomatitis, abdominal pain, dyspepsia, flatulence, gastrointestinal bleeding.
General disorders and administration site conditions: Fatigue, pyrexia.
Infections and infestations: Infection (e.g. pneumonia, sepsis, cellulitis).
Investigations: Weight decreased, LFT abnormalities.
Metabolism and nutrition disorders: Anorexia.
Musculoskeletal and connective tissue disorders: Rigors.
Nervous system disorders: Neuropathy, headache.
Psychiatric disorders: Depression.
Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea, epistaxis.
Skin and subcutaneous tissue disorders: Rash, pruritus, dry skin, alopecia, paronychia, folliculitis, acne, skin fissures.
Potentially Fatal: Cerebrovascular accidents, myocardial infarction/ischaemia, gastrointestinal perforation, interstitial lung disease. Rarely, renal failure, hepatic failure, hepatorenal syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis.
MonitoringParameters
Determine EGFR mutation status prior to non-small cell lung carcinoma (NSCLC) treatment. Perform ophthalmologic exam at baseline and reassess for toxicities at 4-8 week of treatment. Monitor LFT, renal function, serum electrolytes, signs and symptoms of dehydration, pulmonary toxicity, and dermatologic toxicity.
Overdosage
Symptoms: Severe adverse reactions including diarrhoea, rash, increased activity of liver aminotransferases. Management: Symptomatic treatment.
Drug Interactions
Increased serum concentration with inhibitors of CYP1A2 (e.g. ciprofloxacin, fluvoxamine) or CYP3A4 (e.g. ketoconazole, voriconazole, ritonavir, saquinavir, erythromycin, clarithromycin), and capecitabine. Decreased serum concentrations with inducers of CYP3A4 (e.g. rifampicin, phenytoin, carbamazepine, barbiturates) or CYP1A2 (e.g. teriflunomide) and pH-altering agents including antacids, PPI (e.g. omeprazole), and H2-receptor antagonists (e.g. ranitidine). Increased risk of bleeding events and increased INR with coumarin-derived anticoagulants (e.g. warfarin). May increase the risk of adverse effects (e.g. rhabdomyolysis) of statins. Altered distribution and/or elimination of erlotinib with concomitant use of P-gp inhibitors (e.g. ciclosporin, verapamil). Increased platinum concentrations with concomitant use of carboplatin and paclitaxel. Increased risk of gastrointestinal perforation with anti-angiogenic agents, corticosteroids, NSAIDs or taxane-based chemotherapy.
Food Interaction
Increased bioavailability with food. Decreased serum concentrations with St. John’s wort. Increased serum concentration with grapefruit or grapefruit juice.
Action
Description: Erlotinib is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. It reversibly inhibits the intracellular phosphorylation of tyrosine kinase associated with EGFR, thereby preventing further downstream signalling and resulting in cell death.
Pharmacokinetics:
Absorption: Absorbed from the gastrointestinal tract. Bioavailability: Approx 100% (with food); approx 60% (without food). Time to peak plasma concentration: Approx 4 hours.
Distribution: Crosses the placenta. Volume of distribution: 232 L. Plasma protein binding: Approx 93%.
Metabolism: Metabolised in the liver mainly by CYP3A4 and to a lesser extent by CYP1A1, CYP1A2 and CYP1C. Metabolic pathways include demethylation, oxidation and aromatic hydroxylation.
Excretion: Via faeces (83%; 1% as unchanged drug), urine (8%; 0.3% as unchanged drug). Elimination half-life: 36.2 hours.
Chemical Structure

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Storage
Store below 30°C.
ATC Classification
L01XE03 - erlotinib ; Belongs to the class of protein kinase inhibitors, other antineoplastic agents. Used in the treatment of cancer.
Disclaimer: This information is independently developed by MIMS based on Erlotinib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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