Erlotinib side effects,indications,dosage and administration

Erlotinib side effects

Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR), is used in the treatment of non-small cell lung cancer and pancreatic cancer. Like all medications, it has potential side effects.

Common side effects:

1. Rash and dry skin
2. Diarrhea
3. Nausea and vomiting
4. Loss of appetite
5. Fatigue
6. Joint and muscle pain
7. Itching
8. Inflammation of the skin around the nails (paronychia)
9. Cough
10. Headache
11. Shortness of breath

Less common but more serious side effects may include:

1. Interstitial lung disease (ILD), a condition causing scarring of the lungs
2. Liver problems
3. Eye problems such as dry eyes, keratitis, or blurred vision
4. Blood clots, including pulmonary embolism
5. Gastrointestinal perforation (a hole in the stomach or intestines)

Here are its indications and contraindications:

Indications:

1. Non-Small Cell Lung Cancer (NSCLC): this medicine is indicated for the treatment of patients with NSCLC whose tumors have specific mutations in the epidermal growth factor receptor (EGFR) gene. It is used as a first-line therapy for EGFR-positive metastatic NSCLC and as a maintenance treatment following platinum-based chemotherapy.
2. Pancreatic Cancer: this medicine, in combination with gemcitabine, is indicated for the first-line treatment of patients with metastatic pancreatic cancer.

Contraindications:

1. Hypersensitivity: this medicine is contraindicated in patients who have a known hypersensitivity to the drug or any of its excipients.
2. Use of strong CYP3A4 inhibitors: this medicine should not be used concurrently with strong inhibitors of the cytochrome P450 3A4 (CYP3A4) enzyme, as they can increase erlotinib plasma concentrations, leading to potential toxicity.
3. Use of strong CYP3A4 inducers: Similarly, the use of strong CYP3A4 inducers should be avoided as they can decrease erlotinib plasma concentrations, reducing its efficacy.
4. Pregnancy and Breastfeeding: Erlotinib can be harmful to a developing fetus and is contraindicated in pregnant women. It is also not recommended for use in breastfeeding women, as it is not known if the drug is excreted in human milk.
5. Pediatric Use: Erlotinib has not been studied in pediatric patients, and its use in children is not recommended.

It is essential for healthcare providers to assess the benefits and risks of erlotinib therapy for each patient, considering individual patient characteristics, the specific cancer type, and the presence of any contraindications or precautions.

The dosage and administration

The dosage and administration of erlotinib can vary depending on the indication (non-small cell lung cancer or pancreatic cancer) and the patient’s individual circumstances. Here is a general outline of the usage and dosage:

Non-Small Cell Lung Cancer (NSCLC):

• The recommended dose in the treatment of NSCLC is 150 mg taken orally once daily.

Pancreatic Cancer:

• When used in combination with gemcitabine for the treatment of pancreatic cancer, the recommended dose of erlotinib is also 100 mg taken orally once daily.

Administration:

1. Erlotinib should be taken with a glass of water, with or without food.
2. The tablets should not be chewed, crushed, or split.
3. If a dose is missed, it should not be made up; instead, the next dose should be taken as scheduled.
4. Erlotinib should be continued as long as the patient is benefiting from the treatment without unacceptable side effects.

Dose Adjustments:

• Erlotinib dosing may need to be adjusted in patients with severe hepatic impairment (Child-Pugh class C) or when used with strong CYP3A4 inhibitors or inducers.
• If severe adverse reactions occur, the dose may be reduced or temporarily interrupted, and treatment may be resumed at a lower dose if the adverse reactions are resolved.

Monitoring:

• Patients should be monitored for rash and diarrhea, which are common side effects that may require management or dose modification.
• Regular monitoring of lung function is important, as it can rarely cause interstitial lung disease, which may necessitate discontinuation of the drug.

It is crucial that patients take erlotinib exactly as prescribed by their healthcare provider. Any questions or concerns about the dosage and administration of erlotinib should be discussed with a healthcare professional.

When comparing to other EGFR TKIs, such as gefitinib, afatinib, osimertinib, and dacomitinib, several potential advantages and disadvantages can be identified based on clinical data, side effect profiles, and mechanisms of action.

Advantages

1. Approval in NSCLC and Pancreatic Cancer: this medicine is approved for the treatment of both non-small cell lung cancer (NSCLC) and pancreatic cancer, providing versatility in its use.
2. Oral Administration: Erlotinib is taken orally, which is convenient for patients and can reduce the need for hospital visits compared to intravenous treatments.
3. Well-Studied: Erlotinib has been on the market for a considerable period, and its efficacy and safety profiles are well-documented through extensive clinical trials and real-world use.
4. Response Rate: In patients with EGFR mutation-positive NSCLC, erlotinib can have a high response rate, leading to tumor shrinkage and symptom improvement.

Disadvantages

1. Resistance Development: Over time, tumors can develop resistance to erlotinib, often due to secondary mutations in the EGFR gene, such as the T790M mutation.
2. Side Effect Profile: Erlotinib is known for its side effects, which can include rash, diarrhea, and nail changes. These can be managed but may affect the quality of life for some patients.
3. Intrinsic Activity: Compared to newer generation EGFR inhibitors like osimertinib, erlotinib may have less intrinsic activity against certain resistance mutations, limiting its effectiveness in these cases.
4. Pharmacokinetics: Erlotinib has a pharmacokinetic profile that may require careful dosing and monitoring, particularly in patients with liver impairment or those taking medications that interact with erlotinib’s metabolism.
5. Selectivity: While this medicine is selective for EGFR, it is less selective than some newer agents, which may target specific EGFR mutations with greater precision, potentially reducing off-target effects.

US market

Erlotinib has a relatively small market size in the US NSCLC treatment market, but it remains an important treatment option. The sales in the US for the full year of 2020 were approximately $113 million. According to IQVIA data, Erlotinib’s market share in the NSCLC treatment market was 0.9% of the total NSCLC treatment market sales for the full year of 2020. The manufacturers in the US are Roche and Astellas Pharma. In the joint development and sales, Roche and Astellas Pharma are responsible for different tasks. Roche is responsible for the production and sales worldwide, while Astellas Pharma is responsible for the production and sales in the United States and Canada.