Erlotinib

Erlotinib tablets are a targeted cancer therapy approved for two main conditions:

• Non-small cell lung cancer (NSCLC): For patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, confirmed by an FDA-approved test. Can be used as first-line treatment, maintenance therapy, or second/third-line treatment after prior chemotherapy.
• Pancreatic cancer: For first-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer — used in combination with gemcitabine only.
• Erlotinib tablets are not recommended alongside platinum-based chemotherapy.
• Erlotinib tablets are not established for NSCLC patients whose tumors have EGFR mutations other than exon 19 deletion or exon 21 (L858R).

Erlotinib is a kinase inhibitor — it blocks a signaling protein called EGFR (epidermal growth factor receptor) that sits on the surface of cancer cells. In some tumors, EGFR sends constant growth signals, driving the cancer forward. Erlotinib reversibly locks onto EGFR and shuts down this signaling pathway, slowing tumor growth and survival. It has a particularly strong grip on the mutated forms of EGFR found in certain lung cancers (exon 19 deletion and exon 21 L858R mutation).

Because erlotinib binds these mutations more tightly than normal EGFR, it is especially effective in patients whose tumors carry these specific gene changes — which is why testing for those mutations before starting treatment matters.

Erlotinib tablets are taken once daily by mouth. They must be swallowed on an empty stomach — at least one hour before eating or two hours after a meal. Food greatly increases the amount absorbed, which can lead to more side effects, so the timing rule is important.

• For NSCLC, the tablet is taken once daily until the cancer progresses or side effects become intolerable.
• For pancreatic cancer, erlotinib tablets are taken once daily alongside gemcitabine until disease progression or unacceptable toxicity.

Never change your dose or stop without talking to your prescriber first. If side effects occur, your doctor may temporarily hold or adjust your dose rather than stopping treatment entirely.

The most common side effects with erlotinib tablets are rash and diarrhea, which typically start within the first month of treatment.

• Rash (often acne-like) — affects up to 85% of some patient groups; usually manageable
• Diarrhea — very common; tell your doctor if it becomes severe or uncontrolled
• Loss of appetite
• Fatigue or weakness
• Nausea and vomiting
• Cough and shortness of breath
• Dry skin and itching
• Mouth sores

Serious reactions — including dangerous lung inflammation, liver failure, severe skin blistering, eye damage, gut perforation, and bleeding — require immediate medical attention. Contact your healthcare team right away if you notice any sudden or severe new symptoms.

• Interstitial lung disease (ILD): Serious and sometimes fatal lung inflammation has occurred. Stop taking erlotinib and contact your doctor immediately if you develop new shortness of breath, cough, or fever.
• Liver toxicity: Liver failure — including fatal cases — can occur even in people with normal liver function before starting. Regular liver tests are required during treatment.
• Gastrointestinal perforation: A hole can develop in the stomach or intestines — this is rare but dangerous and requires permanently stopping erlotinib.
• Severe skin reactions: Blistering and peeling conditions (including Stevens-Johnson syndrome) have occurred and can be life-threatening; stop treatment immediately.
• Eye disorders: Dry eyes, corneal damage, and ulceration have been reported; serious eye problems require holding or stopping treatment.
• Bleeding risk with warfarin: Erlotinib can raise INR levels in people taking warfarin, leading to serious or fatal bleeding — close monitoring of INR is essential.
• Stroke and blood disorders in pancreatic cancer: Patients receiving erlotinib plus gemcitabine have a higher rate of stroke (cerebrovascular accident) and a rare but serious blood disorder called microangiopathic hemolytic anemia with thrombocytopenia.
• Fetal harm: Erlotinib can cause loss of pregnancy and harm to a developing baby — effective contraception is required during treatment and for one month after the final dose.

Erlotinib's levels in your blood can be significantly raised or lowered by other medications, foods, and habits — which can either increase toxicity or reduce effectiveness.

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, voriconazole, grapefruit juice): Raise erlotinib levels — avoid if possible; dose may need to be reduced.
• CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, St. John's wort): Lower erlotinib levels, reducing effectiveness — avoid if possible; dose may need to be increased.
• Cigarette smoking (CYP1A2 inducer): Significantly lowers erlotinib blood levels — inform your prescriber if you smoke; dose adjustments may be needed.
• Proton pump inhibitors (e.g., omeprazole): Reduce erlotinib absorption substantially — avoid combining if possible.
• H-2 blockers (e.g., ranitidine): Also reduce absorption — careful timing adjustments are required.
• Warfarin and coumarin blood thinners: Erlotinib raises INR and bleeding risk — frequent INR monitoring is required.
• Ciprofloxacin (combined CYP3A4 and CYP1A2 inhibitor): Increases erlotinib exposure — use with caution.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Pregnancy: Erlotinib can cause fetal harm and pregnancy loss — tell your doctor immediately if you are pregnant or become pregnant during treatment.
• Breastfeeding: Do not breastfeed while taking erlotinib or for 2 weeks after the last dose due to potential serious harm to infants.
• Contraception: Females of childbearing potential must use effective birth control during treatment and for 1 month after the final dose.
• Liver disease: Patients with pre-existing liver problems are at higher risk of severe liver toxicity — more frequent monitoring is required, and dose adjustments or discontinuation may be necessary.
• Kidney function: The effect of severely reduced kidney function on erlotinib is not fully known; severe kidney toxicity during treatment requires holding the drug.
• Children: Safety and effectiveness in pediatric patients have not been established.
• Older adults (65+): No overall differences in safety or effectiveness compared to younger adults, but close monitoring is still important.
• Smokers: Smoking substantially lowers drug levels — always disclose your smoking status to your prescriber before and during treatment.

If too much erlotinib is taken, treatment should be held right away and supportive care given to manage symptoms. There is no specific antidote described on the label. If you suspect an overdose, contact a poison control center or seek emergency medical care immediately.

After swallowing an erlotinib tablet, about 60% of the dose is absorbed, with peak blood levels reached around 4 hours after dosing. Food dramatically increases absorption — nearly doubling it — which is why the drug must be taken on an empty stomach to keep levels consistent. Erlotinib is broken down mainly by liver enzymes (CYP3A4, and to a lesser extent CYP1A2), and it leaves the body primarily in the feces, with a small amount in urine. Its half-life (the time it takes for half the drug to clear from the body) is about 36 hours, meaning it takes roughly 7 to 8 days to reach steady, stable levels in the blood. Cigarette smoking speeds up how quickly the body clears erlotinib, significantly reducing blood levels in current smokers.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) .