Erlotinib

393.44

393.44

1312995-182-4

J4T82NDH7E

DTXSID8046454

C65530

L01EB02|L01XE03|L - Antineoplastic and immunomodulating agents

29335990

74.7

3.3

1.24

159-160 °C

553.6°C at 760 mmHg

288.6±30.1 °C

1.615

Very slightly soluble (hydrochloride salt - maximal solubility of approximately 0.4 mg/mL occurs at a pH of approximately 2)

Store at 25 deg C (77 deg F); excursions permitted to 15 - 30 deg C (59 - 86 deg F).

7.06X10-11 mm Hg at 25 deg C (est)

Henry's Law constant = 1.03X10-17 atm-cu m/mol at 25 °C (est)

pKa = 5.18 (benzylimine) (est)

MW: 429.90. MP: 228-230 °C. pKa (25 °C): 5.42. Solubility in water (pH approx 2): approximately 0.5 mg/mL. Slightly soluble in methanol. Practically insoluble in acetonitrile, acetone, ethyl acetate /Erlotinib hydrochloride/

24/25

P201, P202, P260, P261, P264, P270, P271, P273, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P314, P321, P330, P332+P313, P337+P313, P362, P391, P403+P233, P405, P501

H302

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The contaminated filters must be removed, bagged in thick plastic and prepared for disposal in a hazardous waste dump site or incinerator licensed by the Environmental Protection Agency (EPA). /Antineoplastic agents/|For more Disposal Methods (Complete) data for Erlotinib (8 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including erlotinib hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Erlotinib hydrochloride/

|Warning|H302 (25%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P264, P270, P273, P281, P301+P312, P308+P313, P330, P391, P405, and P501|Aggregated GHS information provided by 12 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lots; therefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers who are not protected by the containment environment of a biohazard cabinet should use respiratory protection when handling hazardous drugs. Respiratory protection should be an adjunct to and not a substitute for engineering controls. Surgical masks of all types provide no respiratory protection against powdered or liquid aerosols of hazardous drugs. In situations where workers may be exposed to potential eye contact with hazardous drugs, an appropriate plastic face shield or splash goggles should be worn. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ During compounding of hazardous drugs (eg, crushing, dissolving, and preparing an ointment), workers should wear low permeability gowns and double gloves. Compounding should take place in a protective area such as a disposable glove box. If compounding must be done in the open, an area away from drafts and traffic must be selected, and the worker should use appropriate respiratory protection. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair); low-permeability, disposable protective garments (coveralls or gown and shoe covers); safety glasses or splash goggles; respirator; absorbent, plastic-backed sheets or spill pads; disposable toweling; at least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label); a disposable scoop for collecting glass fragments; and a puncture-resistant container for glass fragments. All individuals who routinely handle hazardous drugs must be trained in proper spill management and cleanup procedures. Spills and breakages must be cleaned up immediately according to the following procedures. If the spill is not located in a confined space, the spill area should be identified and other people should be prevented from approaching and spreading the contamination. Wearing protective apparel from the spill kit, workers should remove any broken glass fragments and place them in the puncture-resistant container. Liquids should be absorbed with a spill pad; powder should be removed with damp disposable gauze pads or soft toweling. The hazardous material should be completely removed and the area rinsed with water and then cleaned with detergent. The spill cleanup should proceed progressively from areas of lesser to greater contamination. The detergent should be thoroughly rinsed and removed. All contaminated materials should be placed in the disposal bags provided and sealed and transported to a designated containment receptacle. Spills occurring in the biohazard cabinet should be cleaned up immediately; a spill kit should be used if the volume exceeds 150 ml or the contents of one drug vial or ampule. If there is broken glass, utility gloves should be worn to remove it and place it in the puncture-resistant container located in the biohazard cabinet. The biological safety cabinet, including the drain spillage trough, should be thoroughly cleaned. If the spill is not easily and thoroughly contained, the biological safety cabinet should be decontaminated after cleanup. If the spill contaminates the high efficiency particulate air filter, use of the biological safety cabinet should be suspended until the cabinet has been decontaminated and the high efficiency particulate air filter replaced. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ If hazardous drugs are routinely prepared or administered in carpeted areas, special equipment is necessary to remove the spill. Absorbent powder should be substituted for pads or sheets and left in place on the spill for the time recommended by the manufacturer. The powder should then be picked up with a small vacuum unit reserved for hazardous drug cleanup. The carpet should then be cleaned according to usual procedures. The vacuum bag should be removed and discarded or cleaned, and the exterior of the vacuum cleaner should be washed with detergent and rinsed before being covered and stored. The contaminated powder should be discarded into a sealable plastic bag and segregated with other contaminated waste materials. Alternatively, inexpensive wet or dry vacuum units may be purchased for this express use and used with appropriate cleaners. All such units are contaminated, once used, and must be cleaned, stored, and ultimately discarded /properly/ ... The circumstances and handling of spills should be documented. Health-care personnel exposed during spill management should also complete an incident report or exposure form. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions (eg, cytotoxics). One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. Damaged shipping cartons of hazardous drugs should be received and opened in an isolated area (eg, in a laboratory fume hood, if available, not in a vertical laminar airflow biological safety cabinet used for preparing sterile products). /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Facilities (eg, shelves, carts, counters, and trays) for storing hazardous drugs are designed to prevent breakage and to limit contamination in the event of leakage. Bins, shelves with barriers at the front, or other design features that reduce the chance of drug containers falling to the floor should be used. Hazardous drugs requiring refrigeration should be stored separately from nonhazardous drugs in individual bins designed to prevent breakage and to contain leakage. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The pharmacy should provide access to information on toxicity, treatment of acute exposure (if available), chemical inactivators, solubility and stability of hazardous drugs (including investigational agents) used in the workplace. /Antineoplastic agents/|For more Preventive Measures (Complete) data for Erlotinib (19 total), please visit the HSDB record page.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/

Symptoms of overdose include diarrhea, rash, and liver transaminase elevation. The most common adverse reactions (>50%) in NSCLC are rash, diarrhea, anorexia and fatigue. The most common adverse reactions (>50%) in pancreatic cancer are fatigue, rash, nausea and anorexia.

Elevations in serum aminotransferase levels are common during erlotinib therapy of pancreatic and lung cancers, and values above 5 times the upper limit of normal occur in at least 10% of patients. Similar rates of ALT elevations, however, can occur with comparable antineoplastic regimens. The abnormalities are usually asymptomatic and self-limited, but may require dose adjustment or discontinuation (Case 1). In addition, there have been rare reports of clinically apparent liver injury attributed to erlotinib therapy. The time to onset is typically within days or weeks of starting therapy, and the liver injury can be severe, there being at least a dozen fatal instances reported in the literature. The onset of injury can be abrupt and the pattern of serum enzyme elevations is usually hepatocellular (Case 2). Immunoallergic features (rash, fever and eosinophilia) are not common and autoantibody formation has not been reported. Routine monitoring of liver tests during therapy is recommended. The rate of clinically significant liver injury and hepatic failure is increased in patients with preexisting cirrhosis or hepatic impairment due to liver tumor burden.

Because cigarette smoking reduces systemic exposure to erlotinib, patients should be advised to stop smoking. If patients continue to smoke, an increase in erlotinib dosage may be considered; upon smoking cessation, dosage of erlotinib should be reduced immediately to the starting dose level.|Drugs that increase the pH of the upper GI tract decrease the solubility of erlotinib and reduce its bioavailability.1 Concomitant administration of omeprazole, a proton pump inhibitor, decreased the area under the concentration-time curve for erlotinib by 46% and decreased the maximum concentration of erlotinib by 61%. Increasing the dose level of erlotinib is not likely to compensate for the loss of exposure, and separation of doses may not eliminate the interaction because proton pump inhibitors have an extended effect on the pH of the upper GI tract. If possible, the concomitant use of erlotinib and proton pump inhibitors should be avoided.|The use of antacids may be considered as an alternative to histamine 2 receptor blockers or proton pump inhibitors in patients receiving erlotinib. However, the effect of antacids on the disposition of erlotinib has not been studied. If use of an antacid is necessary, the antacid dose and the erlotinib dose should be separated by several hours.|Potential pharmacologic interaction (increased international normalized ratio [INR] and infrequent reports of bleeding, including GI and non-GI bleeding). Monitor prothrombin time (PT) or INR regularly in patients receiving erlotinib concomitantly with warfarin or other coumarin-derivative anticoagulants.|For more Interactions (Complete) data for Erlotinib (7 total), please visit the HSDB record page.

Because erlotinib undergoes hepatic metabolism and biliary excretion, the drug should be used with caution in patients with hepatic impairment.|Patients with a history of peptic ulcer disease or diverticulitis and those who are receiving concomitant therapy with antiangiogenesis drugs, corticosteroids, nonsteroidal anti-inflammatory agents (NSAIAs), and/or taxane-based chemotherapy are at increased risk for perforation while receiving erlotinib therapy.|Because cigarette smoking reduces systemic exposure to erlotinib, patients should be advised to stop smoking. If patients continue to smoke, an increase in erlotinib dosage may be considered; upon smoking cessation, dosage of erlotinib should be reduced immediately to the starting dose level.

93% protein bound to albumin and alpha-1 acid glycoprotein (AAG)

Erlotinib is indicated for: - The treatment of metastatic non-small cell lung cancer (NSCLC) with tumors showing epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. - In combination with first-line treatment for patients diagnosed with locally advanced, unresectable or metastatic pancreatic cancer. The safety and efficacy of erlotinib have not been established for patients with NSCLC whose tumors show other EGFR mutations. Additionally it is not recommended for use in combination with platinum-based chemotherapy.|FDA Label|Non-small cell lung cancer (NSCLC)Tarceva is also indicated for switch maintenance treatment in patients with locally advanced or metastatic non-small cell lung cancer with EGFR activating mutations and stable disease after first-line chemotherapy.Tarceva is also indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.In patients with tumours without EGFR activating mutations, Tarceva is indicated when other treatment options are not considered suitable.When prescribing Tarceva, factors associated with prolonged survival should be taken into account.No survival benefit or other clinically relevant effects of the treatment have been demonstrated in patients with Epidermal Growth Factor Receptor (EGFR)-IHC - negative tumours.Pancreatic cancerTarceva in combination with gemcitabine is indicated for the treatment of patients with metastatic pancreatic cancer.When prescribing Tarceva, factors associated with prolonged survival should be taken into account.

Erlotinib is a tyrosine kinase receptor inhibitor that is used in the therapy of advanced or metastatic pancreatic or non-small cell lung cancer. Erlotinib therapy is associated with transient elevations in serum aminotransferase levels during therapy and rare instances of clinically apparent acute liver injury.

Antineoplastic Agents

Erlotinib hydrochloride monotherapy is indicated for the maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. /Included in US product label/|Erlotinib hydrochloride monotherapy is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. /Included in US product label/|Erlotinib hydrochloride in combination with gemcitabine is indicated for the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer. /Included in US product label/

The manufacturer states that there are no known contraindications to the use of erlotinib.|Serious, sometimes fatal, interstitial lung disease-like events have occurred in patients receiving erlotinib. Interstitial lung disease-like events have been reported in approximately 0.7% of about 4900 patients receiving erlotinib in controlled and uncontrolled studies. In the principal efficacy study for non-small cell lung cancer, the reported incidence of interstitial lung disease-like events (0.8%) was similar among patients receiving erlotinib and those receiving placebo. In the principal efficacy study for pancreatic cancer, interstitial lung disease-like events occurred in 2.5% of patients receiving erlotinib and gemcitabine versus 0.4% of those receiving placebo and gemcitabine. Onset of manifestations occurred from 5 days to more than 9 months (median: 39 days) after initiating erlotinib therapy. Reported diagnoses in patients suspected of having interstitial lung disease-like events included pneumonitis, radiation pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, pulmonary fibrosis, acute respiratory distress syndrome, and lung infiltration. Among patients receiving erlotinib for non-small cell lung cancer, most of these cases were associated with confounding or contributing factors, including concomitant or prior chemotherapy, prior radiotherapy, preexisting parenchymal lung disease, metastatic lung disease, or pulmonary infections.|Interruption or discontinuance of erlotinib therapy may be required in patients experiencing pulmonary toxicity.|Hepatorenal syndrome or acute renal failure, sometimes fatal, and renal insufficiency, with or without hypokalemia, have been reported in patients receiving erlotinib. Factors contributing to these adverse renal effects included baseline hepatic impairment; severe dehydration caused by diarrhea, vomiting, and/or anorexia; and concurrent chemotherapy. If dehydration occurs, erlotinib therapy should be interrupted and rehydration measures should be initiated. Periodic monitoring of renal function and serum electrolytes is recommended in patients at risk of dehydration.|For more Drug Warnings (Complete) data for Erlotinib (27 total), please visit the HSDB record page.

Agents that inhibit PROTEIN KINASES. (See all compounds classified as Protein Kinase Inhibitors.)|Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)

Erlotinib is about 60% absorbed after oral administration and its bioavailability is substantially increased by food to almost 100%. Peak plasma levels occur 4 hours after dosing. The solubility of erlotinib is pH dependent. Solubility decreases pH increases. Smoking also decrease the exposure of erlotinib.|Following a 100 mg oral dose, 91% of the dose was recovered in which 83% was in feces (1% of the dose as unchanged parent compound) and 8% in urine (0.3% of the dose as unchanged parent compound).|Apparent volume of distribution = 232 L|Smokers have a 24% higher rate of erlotinib clearance.|Erlotinib is about 60% absorbed after oral administration and its bioavailability is substantially increased by food to almost 100%. Peak plasma levels occur 4 hours after dosing. The solubility of erlotinib is pH dependent. Erlotinib solubility decreases as pH increases.|Following absorption, erlotinib is approximately 93% protein bound to plasma albumin and alpha-1 acid glycoprotein. Erlotinib has an apparent volume of distribution of 232 liters.|Time to reach steady state plasma concentration /is/ 7 - 8 days. No significant relationships of clearance to covariates of patient age, body weight or gender were observed. Smokers had a 24% higher rate of erlotinib clearance.|Following a 100 mg oral dose, 91% of the dose was recovered: 83% in feces (1% of the dose as intact parent) and 8% in urine (0.3% of the dose as intact parent).|For more Absorption, Distribution and Excretion (Complete) data for Erlotinib (10 total), please visit the HSDB record page.

Metabolism occurs in the liver. In vitro assays of cytochrome P450 metabolism showed that erlotinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, and the extrahepatic isoform CYP1A1.|Metabolism and excretion of erlotinib, an orally active inhibitor of epidermal growth factor receptor tyrosine kinase, were studied in healthy male volunteers after a single oral dose of (14)C-erlotinib hydrochloride (100-mg free base equivalent, approximately 91 microCi/subject)... In plasma, unchanged erlotinib represented the major circulating component, with the pharmacologically active metabolite M14 accounting for approximately 5% of the total circulating radioactivity. Three major biotransformation pathways of erlotinib are O-demethylation of the side chains followed by oxidation to a carboxylic acid, M11 (29.4% of dose); oxidation of the acetylene moiety to a carboxylic acid, M6 (21.0%); and hydroxylation of the aromatic ring to M16 (9.6%). In addition, O-demethylation of M6 to M2, O-demethylation of the side chains to M13 and M14, and conjugation of the oxidative metabolites with glucuronic acid (M3, M8, and M18) and sulfuric acid (M9) play a minor role in the metabolism of erlotinib. The identified metabolites accounted for >90% of the total radioactivity recovered in urine and feces. The metabolites observed in humans were similar to those found in the toxicity species, rats and dogs.|Erlotinib has known human metabolites that include Erlotinib M14.

Median half-life of 36.2 hours.|A population pharmacokinetic analysis in 591 patients receiving the single-agent erlotinib hydrochloride 2nd/3rd line regimen showed a median half-life of 36.2 hours.

The mechanism of clinical antitumor action of erlotinib is not fully characterized. Erlotinib inhibits the intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor (EGFR). Specificity of inhibition with regard to other tyrosine kinase receptors has not been fully characterized. EGFR is expressed on the cell surface of normal cells and cancer cells.|Although the exact mechanism of antineoplastic activity of erlotinib has not been fully elucidated, erlotinib appears to inhibit the intracellular phosphorylation of tyrosine kinase associated with EGFR, which is expressed on the surface of normal and cancer cells. Specificity with regard to other tyrosine kinase receptors has not been fully characterized.|Erlotinib is a potent inhibitor of epidermal growth factor receptor tyrosine kinase and has been demonstrated to treat advanced or metastatic non-small cell lung cancer to prolong survival after failure of first-line or second-line chemotherapy. However, little is known about its effects on immune system. In the present study, /investigators/ aimed to investigate the immunosuppressive activity of erlotinib on T lymphocytes both in vitro and in vivo, and further explore its potential molecular mechanism. Erlotinib exerted a significant inhibition on the T cell proliferation and activation induced by concanavalin A, anti-CD3 plus anti-CD28, staphylococcal enterotoxin B or phorbol myristate acetate respectively in a concentration-dependent manner and it also inhibited the secretion of the proinflammatory cytokines such as IL-2 and IFN-gamma of activated T cells. Further study showed that erlotinib caused G0/G1 arrest and suppressed the phosphorylations of c-Raf, ERK and Akt in activated T cells. Moreover, erlotinib significantly ameliorated picryl chloride-induced ear contact dermatitis in a dose-dependent manner in vivo. In summary, these findings suggest that erlotinib may cause the impairment of T-cell-mediated immune response both in vitro and in vivo through inhibiting T cell proliferation and activation, which is closely associated with its potent down-regulation of the c-Raf/ERK cascade and Akt signaling pathway.

In case of suspected overdose, erlotinib should be withheld and symptomatic treatment instituted.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ ... In the present report, unusual hematologic complications were detected after erlotinib was administered as second-line monotherapy in pretreated patients with advanced non-small cell lung cancer. Four patients pre-treated with cisplatin or its analog-based combinations, were evaluated. Erlotinib was given at a dose of 150 mg daily. In cases of intolerable adverse reactions, the dose was either reduced to 100 mg daily or treatment was interrupted for a maximum of two weeks. Serious hematologic toxicity (or complications) developed in these 4 patients after 4-8.5 months of treatment. Two patients developed leukemias (AML, CML) and two, myelodysplastic syndrome. Whether or not these hematologic complications were related to erlotinib treatment is comprehensively discussed.|/SIGNS AND SYMPTOMS/ Single oral doses of erlotinib up to 1,000 mg in healthy subjects and weekly doses up to 1,600 mg in cancer patients have been tolerated. Repeated twice-daily doses of 200 mg single-agent erlotinib in healthy subjects were poorly tolerated after only a few days of dosing. Based on the data from these studies, an unacceptable incidence of severe adverse reactions, such as diarrhea, rash, and liver transaminase elevation, may occur above the recommended dose.|/CASE REPORTS/ ...The use of EGFR-TKI is associated with unique and dramatic dermatologic side effects. /Investigators/ report 2 patients with non small cell lung cancer developing a typical acneiform (papulo-pustular) eruption shortly after initiation of EGFR-TKI /therapy with erlotinib/.|/CASE REPORTS/ ... A 59-year-old man, who was referred to a cornea service, presented with blurred vision and pain OD. Visual acuity was 6/20. Slit-lamp examination showed a severe corneal epithelial defect and ocular inflammation OD. Eighteen months previously, he had been diagnosed with lung cancer and had been undergoing treatment with erlotinib for 6 months. He had no history of ocular surgery, trauma or diabetes. After topical antibiotic therapy was started and the erlotinib treatment was discontinued for 1 week, the corneal findings resolved completely. The visual acuity recovered to 20/20 after 8 weeks. An EGFR inhibitor used to treat lung cancer can cause severe corneal disorders including severe corneal defects and ocular inflammation. Clinicians should consider the possibility of erlotinib in cases of corneal disorders of uncertain etiology.|For more Human Toxicity Excerpts (Complete) data for Erlotinib (22 total), please visit the HSDB record page.

11C erlotinib

Erlotinib Hydrochloride preparations (AHFS, 2012)

HPLC determination in plasma

Human drugs -> Tarceva -> EMA Drug Category|Antineoplastic agents -> Human pharmacotherapeutic group|Human drugs -> Rare disease (orphan)