Erlotinib

Erlotinib is used in the treatment of non-small cell lung cancer and pancreatic cancer. Erlotinib should be taken on an empty stomach or should be taken one hour before or 2 hours after meal. You should continue to take it as long as your doctor advises it.

Erlotinib is an anti-cancer medication. Epidermal growth factor receptors (EGFR) are expressed on the lung cancer cell surfaces that modulate their growth. This medicine works by binding the chemical messenger, EGFR, hence, inhibits the cancer signaling pathways mediated by EGFR. This is how it restricts further growth of the cancer cells.

• Non-Small Cell Lung Cancer (NSCLC): First-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 substitution mutations.
• Pancreatic Cancer: First-line treatment of locally advanced, unresectable or metastatic pancreatic cancer in combination with gemcitabine.

Targeted Cancer Therapy

EGFR Tyrosine Kinase Inhibitor

Erlotinib, a kinase inhibitor, is a quinazolinamine. It reversibly inhibits the kinase activity of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor and thereby inhibiting further downstream signaling. Erlotinib binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations is higher than its affinity for the wild-type receptor.

Erlotinib is an epidermal growth factor receptor/human epidermal growth factor receptor type 1 (EGFR/HER1) tyrosine kinase inhibitor. It reversibly inhibits the kinase activity of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor, thereby inhibiting further downstream signaling and resulting in cell death.

Adult Dose:

• NSCLC: 150 mg PO once daily (empty stomach); continue until disease progression or unacceptable toxicity.
• Pancreatic Cancer (with gemcitabine): 100 mg PO once daily (empty stomach); continue until disease progression or unacceptable toxicity.
• With strong CYP3A4 inhibitors: Reduce by 50 mg decrements.
• With CYP3A4 inducers: Increase by 50 mg increments at 2-week intervals (max 450 mg).
• Smoking patients: Increase by 50 mg increments at 2-week intervals (max 300 mg); reduce dose upon smoking cessation.

Hepatic Impairment: Mild-moderate: No dosage adjustment needed; Severe: Limited data.

Renal Impairment: Safe; no dose adjustment recommended (severe kidney disease: not advised).

Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Erlotinib is to be taken on an empty stomach (1 hour before or 2 hours after meal).

If you miss a dose of Erlotinib, skip it and continue with your normal schedule. Do not double the dose.

Common Side Effects (≥20%):

• Rash
• Diarrhea
• Anorexia/Decreased appetite
• Fatigue
• Dyspnea
• Cough
• Nausea
• Vomiting
• Abdominal pain
• Weight loss
• Stomatitis

Serious Side Effects: Interstitial Lung Disease (ILD), Renal Failure, Hepatotoxicity, Gastrointestinal Perforation, Bullous and Exfoliative Skin Disorders, MI/Ischemia, Cerebrovascular Accident.

Precautions:

• It is not known whether Erlotinib alters the ability to drive. Do not drive if you experience any symptoms that affect your ability to concentrate and react.
• Take on an empty stomach (1 hour before or 2 hours after meal).
• Diarrhea may occur; drink plenty of fluids and inform doctor if blood in stools.
• Use reliable contraceptive method during treatment and for one month after stopping.
• Makes skin sensitive to sunlight; apply sunscreen or wear protective clothing.
• Avoid smoking while taking this medicine.
• Do not take with medications lowering stomach acid (antacids, H2 blockers, PPIs).
• Inform doctor if mouth ulceration, vision changes, worsening cough, or breathing difficulties occur.
• Regular blood tests to monitor liver function required.

Contraindications: Hypersensitivity; Pregnancy and breastfeeding.

Drug Interactions:

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, atazanavir): Increased serum levels.
• CYP3A4 inducers (rifampicin, carbamazepine, phenytoin): May reduce erlotinib exposure.
• CYP1A2 inhibitors (ciprofloxacin): Increased serum levels.
• P-glycoprotein inhibitors (cyclosporine, verapamil): May alter distribution or elimination.
• Drugs increasing gastric pH (antacids, H2 blockers, PPIs): Reduce solubility and bioavailability.
• Warfarin: Increased INR and bleeding events.

Food Interactions: It is not known whether it is safe to consume alcohol with Erlotinib. Consult your doctor. Take on empty stomach.

Use in Pregnancy: Category D. Can cause fetal harm when administered to a pregnant woman. Doctor may prescribe in life-threatening situations if benefits outweigh risks.

Use in Lactation: Erlotinib is probably unsafe to use during breastfeeding. Limited data suggests drug may pass into breastmilk and harm the baby.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: No overall differences in safety or efficacy were observed between subjects 65 years and older and those younger than 65.

Renal Impairment: Safe to use in patients with kidney disease; no dose adjustment recommended. Not advised in severe kidney disease.

Hepatic Impairment: Use with caution. No dose adjustment recommended in mild to moderate liver disease; limited information in severe liver disease.

Overdose: Single oral doses up to 1,000 mg in healthy subjects tolerated. 200 mg twice daily was poorly tolerated. Overdose may cause severe diarrhea, rash, and liver transaminase elevation. Withhold Erlotinib and institute symptomatic treatment.

Storage: Store at a temperature not exceeding 30°C in a dry place. Protect from light and moisture.

Erlotinib