Erlotinib
Pronunciation: (er-LOE-tye-nib)Class: Epidermal growth factor receptor inhibitor
Trade Names:
Tarceva
- Tablets 25 mg
- Tablets 100 mg
- Tablets 150 mg
Pharmacology
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Inhibits intracellular phosphorylation of tyrosine kinase associated with epidermal growth factor receptor.
Pharmacokinetics
Absorption
Approximately 60% after oral administration; increased to almost 100% by food.
Distribution
Approximately 93% protein bound to albumin and alpha-1 acid glycoprotein. Apparent Vd is 232 L.
Metabolism
Metabolized primarily by CYP3A4 and, to a lesser degree, by CYP1A2 and the extrahepatic isoform CYP1A1.
Elimination
About 83% excreted in feces and 8% in urine. The half-life is about 36 h. Smokers had a 24% higher rate of Cl.
Special Populations
Renal Function ImpairmentLess than 9% is excreted in the urine.
Hepatic Function ImpairmentPrimarily cleared by the liver. Use with caution in patients with bilirubin levels 3 times ULN.
Indications and Usage
As monotherapy for the treatment of locally advanced or metastatic non–small cell lung cancer (NSCLC) after failure of at least 1 prior chemotherapy regimen. In combination with gemcitabine as first-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer.
Unlabeled Uses
Treatment of squamous cell head and neck cancer.
Contraindications
Standard considerations.
Dosage and Administration
NSCLCAdults
PO 150 mg at least 1 h before or 2 h after food. Continue treatment until disease progression or unacceptable toxicity occurs.
Pancreatic CancerAdults
PO 100 mg 1 h before or 2 h after food, in combination with gemcitabine. Continue treatment until disease progression or unacceptable toxicity occurs.
Dose ModificationsAdults
PO When dose reduction is necessary, reduce the dose in 50 mg increments. In patients who develop an acute onset of new or progressive pulmonary symptoms (eg, cough, dyspnea, fever), interrupt treatment pending diagnostic evaluation. If interstitial lung disease is diagnosed, discontinue erlotinib and institute appropriate treatment. Patients who become dehydrated or who develop severe skin reactions may require dose reduction or temporary interruption of therapy. In patients receiving a strong CYP3A4 inhibitor, consider a dose reduction. In patients receiving CYP3A4 inducers, alternative treatment lacking CYP3A4 inducing activity is strongly recommended. If an alternative is unavailable, consider increasing the dose of erlotinib, as tolerated, at 2-wk intervals. Reduce the erlotinib dose immediately after discontinuing the CYP3A4 inducer.
Storage/Stability
Store tablets in at controlled room temperature (59° to 86°F).
Drug Interactions
CYP inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John's wort)May reduce erlotinib plasma concentrations, decreasing the therapeutic effect and necessitating dosage adjustments or changes in therapy.
Drugs that alter upper GI tract pH (eg, omeprazole)Avoid coadministration of erlotinib and proton pump inhibitors. Separate erlotinib and antacid dosing by several hours.
Strong CYP3A4 inhibitors (eg, atazanavir, clarithromycin, grapefruit or grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole)May elevate erlotinib plasma concentrations, increasing the risk of adverse reactions and necessitating dosage reduction.
WarfarinINR elevations and bleeding have been reported with erlotinib coadministration.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Cardiovascular
Pancreatic cancer treatment (erlotinib plus gemcitabine)Arrhythmias, cerebrovascular accidents including cerebral hemorrhage, MI/ischemia, syncope (less than 5%).
CNS
NSCLS treatment (erlotinib alone)Fatigue (52%).
Pancreatic cancer treatment (erlotinib plus gemcitabine)Fatigue (73%); pyrexia (36%); depression (19%); dizziness, headache, insomnia (15%); anxiety, neuropathy (13%).
Dermatologic
NSCLS treatment (erlotinib alone)Rash (75%); pruritus (13%); dry skin (12%).
Pancreatic cancer treatment (erlotinib plus gemcitabine)Rash (69%); alopecia (14%).
EENT
NSCLS treatment (erlotinib alone)Conjunctivitis, keratoconjunctivitis (12%); corneal ulcerations; epistaxis, hair and nail disorders including alopecia, brittle and loose nails, eyebrow/eyelash changes, hirsutism, inflammation of the nail fold with separation from the skin (postmarketing).
GI
NSCLS treatment (erlotinib alone)Diarrhea (54%); anorexia (52%); nausea (33%); vomiting (23%); stomatitis (17%); abdominal pain (11%).
Pancreatic cancer treatment (erlotinib plus gemcitabine)Nausea (60%); anorexia (52%); diarrhea (48%); abdominal pain (46%); vomiting (42%); constipation (31%); stomatitis (22%); dyspepsia (17%); flatulence (13%); ileus, pancreatitis (less than 5%); GI bleeding (postmarketing).
Genitourinary
Pancreatic cancer treatment (erlotinib plus gemcitabine)Renal insufficiency (less than 5%); acute renal failure, renal insufficiency including death (postmarketing).
Hematologic-Lymphatic
Pancreatic cancer treatment (erlotinib plus gemcitabine)Hemolytic anemia (less than 5%); deep vein thrombosis (4%).
Hepatic
Hepatic failure (postmarketing).
Lab Tests
NSCLS treatment (erlotinib alone)Abnormal LFTs.
Pancreatic cancer treatment (erlotinib plus gemcitabine)Elevated ALT (31%); elevated AST (24%); elevated bilirubin (17%).
Metabolic-Nutritional
Pancreatic cancer treatment (erlotinib plus gemcitabine)Weight decrease (39%).
Musculoskeletal
Pancreatic cancer treatment (erlotinib plus gemcitabine)Bone pain (25%); myalgia (21%); rigors (12%).
Respiratory
NSCLS treatment (erlotinib alone)Dyspnea (41%); cough (33%).
Pancreatic cancer treatment (erlotinib plus gemcitabine)Dyspnea (24%); cough (16%).
Miscellaneous
NSCLS treatment (erlotinib alone)Infection (24%).
Pancreatic cancer treatment (erlotinib plus gemcitabine)Infection (39%); edema (37%).
Precautions
MonitorMonitor patient for dermatologic, GI, ophthalmic, respiratory, and general body adverse reactions. Be prepared to reduce the dose or temporarily interrupt therapy if diarrhea unresponsive to loperamide develops, the patient becomes dehydrated, or if severe skin reactions are noted. Periodic LFTs are recommended. Periodic monitoring of renal function and serum electrolytes is recommended in patients at risk of dehydration. |
Pregnancy
Category D .
Lactation
Undetermined.
Children
Safety and efficacy not established.
Hepatic function impairment
Use with caution. Consider periodically evaluating liver function (eg, alkaline phosphatase, bilirubin, transaminases) during treatment with erlotinib. Consider erlotinib dose reduction (in 50 mg increments) or interruption of therapy if severe changes in liver function develop.
Hepatotoxicity
Hepatic failure and hepatorenal syndrome (including fatalities) have been reported, particularly in patients with baseline hepatic impairment.
Pulmonary toxicity
Serious, sometimes fatal, interstitial lung disease has been reported. Monitor patient for acute onset or progression of pulmonary symptoms (eg, cough, dyspnea, fever). If diagnostic evaluation indicates interstitial lung disease, discontinue erlotinib and be prepared to institute appropriate treatment.
Renal failure
Hepatorenal syndrome, acute renal failure, and renal insufficiency have been reported, in some cases associated with severe dehydration due to diarrhea, vomiting, and/or anorexia or concomitant chemotherapy.
Overdosage
Symptoms
Diarrhea, liver transaminase elevations, rash.
Patient Information
- Explain name, action, and potential adverse reactions of the treatment regimen. Review the treatment regimen, including dosing schedule, duration of treatment, and monitoring that will be required.
- Advise patient to take prescribed dose once daily, at least 1 h before or 2 h after meals or snacks.
- Advise patient or caregiver to immediately report noted or significant adverse reactions to health care provider, including any of the following: eye irritation; new onset or worsening of unexplained shortness of breath or cough; severe or persistent diarrhea, nausea, appetite loss, or vomiting.
- Caution woman of childbearing potential to avoid becoming pregnant during therapy. Advise patient to use effective contraceptive methods during and for 2 wk following completion of therapy.
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More Erlotinib resources
erlotinib - Includes detailed dosage instructions.
Compare Erlotinib with other medications for the treatment of:
Non-Small Cell Lung Cancer, Pancreatic Cancer, Renal Cell Carcinoma
