Erlotinib
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Epidermal Growth Factor Receptor (EGFR) inhibitors, Tyrosine kinase inhibitor, Therapy Class:
Antineoplastic agent, Approved Countries
India, the United States, Canada, countries within the European Union, Australia, Japan and South Korea.
Erlotinib is an antineoplastic agent belonging to the pharmacological class of Epidermal Growth Factor Receptor (EGFR) inhibitors.
The FDA approved Erlotinib for treating metastatic non-small cell lung cancer (NSCLC) and pancreatic cancer in combination with other medications.
Erlotinib is absorbed from the gut, showing variable bioavailability with food. It reaches peak concentration in about 4 hours and is widely distributed; it undergoes liver metabolism and is mainly eliminated via faeces, with a 36.2-hour half-life.
The most common side effects of Erlotinib include nausea, vomiting, fatigue, rash, and weight loss.
Erlotinib is available as an oral tablets.
The molecule is available in India, the United States, Canada, countries within the European Union, Australia, Japan and South Korea.
Erlotinib is an antineoplastic agent belonging to the pharmacological class of Epidermal Growth Factor Receptor (EGFR) inhibitors.
Erlotinib's clinical antitumor action mechanism is not entirely known. Erlotinib prevents tyrosine kinase linked to the epidermal growth factor receptor (EGFR) from becoming phosphorylated intracellularly. The degree of inhibition's specificity towards alternative tyrosine kinase receptors remains incompletely understood. Both healthy cells and cancerous cells have EGFR expressed on their surface.
Erlotinib takes approximately 4 hours to reach peak plasma concentration after administration.
Erlotinib is available as an oral tablets.
Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.
The physician recommends taking this medication orally once daily, usually after meals.
- Non-small cell lung cancer
- Pancreatic cancer
Non-small cell lung cancer: Erlotinib, used in treating non-small cell lung cancer (NSCLC), targets specific mutations in the epidermal growth factor receptor (EGFR), inhibiting EGFR tyrosine kinase activity. This action hampers tumour growth and progression. Whether administered alone or combined with other medications, Erlotinib improves progression-free survival, mitigates symptoms, and enhances the quality of life for patients with NSCLC. It's a targeted therapy that effectively impedes the activity of EGFR, offering significant benefits by precisely addressing the underlying mutations driving the cancer, irrespective of whether the patient is a smoker or non-smoker affected by this form of lung cancer.
Pancreatic cancer: When combined with gemcitabine, Erlotinib has shown significant benefits in the treatment of pancreatic cancer. Compared to using gemcitabine alone, this combination therapy results in higher overall survival rates. Erlotinib improves the prognosis of patients with advanced pancreatic cancer by blocking the growth and progression of tumours by targeting the epidermal growth factor receptor (EGFR). Patients have experienced better results from its addition to gemcitabine therapy, such as longer survival times and higher quality of life.
Erlotinib is indicated for:
Non-small cell lung cancer that has spread and whose tumours exhibit deletions in exon 19 of the EGFR or substitution mutations in exon 21 (L858R) of the EGFR.
In combination with initial therapy for individuals identified as having locally advanced, incurable, or metastatic pancreatic cancer.
Orally: Patients take Erlotinib orally, using tablets swallowed with water once daily. The tablets should be ingested whole on an empty stomach, usually 1 hr before or 2 hrs after meals, following the prescribed dosage and timing to ensure effectiveness in treating conditions like non-small cell lung cancer. Patients should refrain from crushing, chewing, or breaking the tablets unless instructed by their healthcare provider. Adherence to these instructions is crucial for the medication to work optimally in managing the specified conditions, emphasizing the importance of following the healthcare professional's guidance for proper administration.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Tablets: 25mg, 100mg, 150mg.
Erlotinib is available as an oral tablets.
Dose Adjustment in Adult Patients:
Non-small Cell Lung Cancer
150 mg PO qDay, either two hours or one hour after meals
Continue until the disease worsens or the toxicity becomes unacceptable.
NSCLC limitations on use
It is not advised to utilize this in conjunction with chemotherapy based on platinum.
It has not been determined whether first-line therapy is safe and effective for patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution.
Pancreatic Cancer
100 mg/day orally with gemcitabine
Continue until the disease worsens or the toxicity becomes unacceptable.
While on Erlotinib, avoid grapefruit or its juice to prevent potential drug metabolism issues. Be wary of medications, supplements, or herbal products that may interact with Erlotinib. No specific dietary restrictions exist, so maintain regular meals, emphasizing adequate hydration.
The dietary restriction should be individualized as per patient requirements.
- Individuals who have known hypersensitivity or allergic reactions to this medication or any of its components.
- Severe hepatic impairment.
- Interstitial Lung Disease (ILD)-like events, including fatalities, have infrequently occurred with Erlotinib. Interrupt Erlotinib if new or progressive unexplained pulmonary symptoms, such as dyspnea, cough, or fever, appear suddenly. Discontinue Erlotinib if ILD is diagnosed.
- Signs of acute renal failure (including fatalities) and renal insufficiency have been reported. Interrupt Erlotinib in cases of dehydration. Regularly monitor renal function and electrolytes in at-risk patients to prevent complications.
- Reported cases of hepatic failure and hepatorenal syndrome (including fatalities) necessitate periodic liver function testing. Interrupt or discontinue Erlotinib if severe liver function changes occur. Monitor closely in patients with hepatic impairment.
- Gastrointestinal perforations, including fatalities, have been documented. Discontinue Erlotinib immediately upon suspicion.
- Bullous and exfoliative skin disorders, including fatalities, have been reported. Interrupt or discontinue Erlotinib in such cases.
- Myocardial infarction/ischemia and cerebrovascular accidents, including fatalities, have occurred in pancreatic cancer patients taking Erlotinib.
- Microangiopathic Hemolytic Anemia, corneal perforation/ulceration, and INR elevations with bleeding events have been reported. Monitor patients on warfarin or similar anticoagulants closely.
- Erlotinib poses a risk of fetal harm; advise women to avoid pregnancy while using Erlotinib due to its potential teratogenic effects.
Alcohol Warning
It is unsafe to consume Erlotinib with alcohol.
Breast Feeding Warning
It is not recommended for use during breastfeeding.
Pregnancy Warning
It is not recommended for use during pregnancy.
Food Warning
Consume an antioxidant-rich diet, and avoid smoking/alcohol.
The adverse reactions related to Erlotinib can be categorized as:
- Common Adverse Effects: Rash, anorexia, diarrhea, fatigue, nausea, infection, vomiting, dyspnea, stomatitis, cough, pruritus, conjunctivitis, dry skin, keratoconjunctivitis sicca, and abdominal pain.
- Less Common Adverse Effects: Elevated liver function tests (grade 2), acne, paronychia, weight loss, pneumonitis with pulmonary infiltrates, and pulmonary fibrosis.
- Rare Adverse Effects: Interstitial lung disease-like events.
Reports on Postmarketing
Disorders related to musculoskeletal system and connective tissue: myopathy, including rhabdomyolysis, combined with statin medication
Eye conditions: Uveitis and other inflammatory conditions of the eyes
The clinically relevant drug interactions of Erlotinib are briefly summarized here.
Drug-Drug Interactions
Increased serum concentration when using capecitabine and CYP1A2 or CYP3A4 inhibitors (such as ciprofloxacin, fluvoxamine, ritonavir, saquinavir, erythromycin, and clarithromycin) together. Reduced concentrations in the serum when exposed to CYP3A4 inducers (like rifampicin, phenytoin, carbamazepine, barbiturates) or CYP1A2 inducers (like teriflunomide), as well as pH-altering substances like antacids, proton pump inhibitors (like omeprazole), and H2-receptor antagonists (like ranitidine). Increased INR and risk of bleeding events when using anticoagulants derived from coumarins (e.g., warfarin). It may raise the possibility of statin side effects (like rhabdomyolysis). P-gp inhibitors (such as ciclosporin and verapamil) taken concurrently with Erlotinib may cause its distribution or elimination changes. Elevated concentrations of platinum when paclitaxel and carboplatin are used simultaneously. Increased risk of gastrointestinal perforation when using corticosteroids, NSAIDs, anti-angiogenic drugs, or chemotherapy based on taxanes.
Food Interactions
Higher bioavailability when consuming food. St John's wort reduced serum concentrations. Grapefruit or grapefruit juice has a higher serum concentration.
The common side effects of Erlotinib include:
Bone pain
stomach ache
Breathlessness
Constipation
Cough
Diarrhea
Fatigue
Loss of weight
Fever
Infection
Pain in the muscles
Nausea
Rash
Stomatitis, or oral inflammation
Vomiting
- Pregnancy
Pregnancy Category D (FDA): Use in cases where no safer medication is available and life is in danger. Positive evidence of prenatal risk in humans.
If Erlotinib is given to a pregnant woman, it may harm the fetus. It should be advised to women who are capable of bearing children not to get pregnant while taking Erlotinib.
When Erlotinib is administered at doses that result in plasma drug concentrations roughly three times those in humans, it has been demonstrated to cause maternal toxicity in rabbits, along with associated embryofetal lethality and abortion (AUCs at 150 mg daily dose). There was no increased incidence of embryofetal lethality or abortion in rabbits or rats when given during the organogenesis period to achieve plasma drug concentrations roughly equivalent to those in humans, based on AUC. However, female rats treated with 30 mg/m2/day or 60 mg/m2/day (0.3 or 0.7 times the clinical dose, on a mg/m2 basis) of erlotinib showed an increase in early resorptions from the first week of pregnancy until mating, which resulted in a decrease in the number of viable fetuses.
When Erlotinib was administered at doses up to 600 mg/m2/day in the rabbit (three times the plasma drug concentration observed in humans at 150 mg/day) and up to 60 mg/m2/day in the rat (0.7 times the clinical dose of 150 mg/day on a mg/m2 basis), no teratogenic effects were observed during organogenesis.
- Nursing Mothers
The excretion of Erlotinib in human milk is unknown. Erlotinib can cause severe adverse reactions in nursing infants. Since many drugs are excreted in human milk, it is essential to consider the importance of the drug to the mother when deciding whether to stop nursing or stop taking it altogether.
- Pediatric Use
As per the FDA, the safety and efficacy of Erlotinib have not been specifically studied in pediatric patients.
- Geriatrics (> 65 years old) Use
Researchers have studied Erlotinib's safety and efficacy in the geriatric population. Elderly patients showed comparable treatment outcomes to younger adults. Although they might face a higher risk of specific adverse effects like rash and diarrhea, healthcare providers recommend closely monitoring and adjusting dosages based on individual tolerability and renal function.
Dose Adjustment in Kidney Impairment Patients:
Less than nine per cent (<9%) of Erlotinib and its metabolites are excreted through the kidney.
Severe renal impairment: Not studied.
Dose Adjustment in Hepatic Impairment Patients:
When receiving Erlotinib therapy, patients with hepatic impairment (total bilirubin > ULN) should be closely watched. Patients whose total bilirubin is more than three times the upper limit of normal should be treated with Erlotinib with extra caution.
The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Erlotinib.
Signs and Symptoms
Overconsumption of Erlotinib could lead to severe adverse reactions, including diarrhoea, rash, and increased activity of liver aminotransferases.
Management
The management of Erlotinib overdose involves supportive measures and symptomatic treatment. There isn't a specific antidote. Immediate gastric lavage or induced vomiting might be considered shortly after ingestion. Due to its long half-life, continuous monitoring for adverse effects, like skin reactions or diarrhoea, is crucial. Supportive care involves maintaining vital functions, managing symptoms aggressively if severe, and monitoring liver function.
Pharmacodynamics
Not available
Pharmacokinetics
Absorption: Erlotinib is absorbed from the gastrointestinal tract, exhibiting varying bioavailability. When taken with food, its bioavailability is approximately 100%, whereas without food, it reduces to around 60%. It takes about 4 hours to reach peak plasma concentration after administration.
Distribution: This medication crosses the placental barrier, distributing extensively throughout the body. Its volume of distribution is approximately 232 litres, and around 93% of Erlotinib binds to plasma proteins.
Metabolism: Primarily metabolized in the liver, Erlotinib undergoes metabolic processes primarily by the CYP3A4 enzyme, with contributions from CYP1A1, CYP1A2, and CYP1C. These pathways involve demethylation, oxidation, and aromatic hydroxylation.
Excretion: The drug is primarily eliminated via faeces, with approximately 83% excreted (with only 1% as an unchanged drug) and a smaller portion via urine (around 8%, with 0.3% as a whole drug). Erlotinib has an elimination half-life of approximately 36.2 hours.
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Published on: 8 Jan 2024 9:57 AM GMT