Round, biconvex, white film coated tablets, debossed with "N 150" on one side and plain on other side.
Each film-coated tablet contains erlotinib hydrochloride equivalent to erlotinib 150 mg.
Excipients with known effect: Each film-coated tablet contains 103.818 mg lactose monohydrate.
Excipients/Inactive Ingredients: Tablet core: Lactose monohydrate, Microcrystalline Cellulose, Sodium starch glycolate, Sodium Lauryl Sulphate, Sodium Stearyl Fumarate.
Tablet coat: Hypromellose, Titanium Dioxide and Macrogol.
Pharmacotherapeutic group: Antineoplastic agent protein kinase inhibitor. ATC code: L01XE03.
Pharmacology: Pharmacodynamics: Mechanism of action: Erlotinib is an epidermal growth factor receptor/human epidermal growth factor receptor type 1 (EGFR also known as HER1) tyrosine kinase inhibitor. Erlotinib potently inhibits the intracellular phosphorylation of EGFR. EGFR is expressed on the cell surface of normal cells and cancer cells. In non-clinical models, inhibition of EGFR phosphotyrosine results in cell stasis and/or death.
EGFR mutations may lead to constitutive activation of anti-apoptotic and proliferation signaling pathways. The potent effectiveness of erlotinib in blocking EGFR-mediated signalling in these EGFR mutation positive tumours is attributed to the tight binding of erlotinib to the ATP-binding site in the mutated kinase domain of the EGFR. Due to the blocking of downstream-signaling, the proliferation of cells is stopped, and cell death is induced through the intrinsic apoptotic pathway. Tumour regression is observed in mouse models of enforced expression of these EGFR activating mutations.
Pharmacokinetics: Absorption: Approximately 60% of an oral dose of erlotinib is absorbed from the GI tract; presence of food in the Gl tract increases oral bioavailability to almost 100%. Peak plasma concentrations of erlotinib occur at 4 hours following oral administration of a 150 mg dose.
Distribution: Erlotinib is approximately 93% protein bound (mainly to albumin and α1-acid glycoprotein).
Biotransformation: Erlotinib is extensively metabolized via the cytochrome P-450 (CYP) enzyme system, mainly by CYP3A4 and, to a lesser extent, by CYP1A1 (principally an extrahepatic enzyme) and CYP1A2.
Elimination: The half-life of erlotinib is approximately 36 hours; the clearance is approximately 24% higher in smokers. Following a 100-mg oral dose, erlotinib is excreted mainly as metabolites in feces (83%) and urine (8%).
Toxicology: Preclinical safety data: Chronic dosing effects observed in at least one animal species or study included effects on the cornea (atrophy, ulceration), skin (follicular degeneration and inflammation, redness, and alopecia), ovary (atrophy), liver (liver necrosis), kidney (renal papillary necrosis and tubular dilatation), and gastrointestinal tract (delayed gastric emptying and diarrhoea). Red blood cell parameters were decreased and white blood cells, primarily neutrophils, were increased. There were treatment-related increases in ALT, AST and bilirubin. These findings were observed at exposures well below clinically relevant exposures.
Based on the mode of action, erlotinib has the potential to be a teratogen. Data from reproductive toxicology tests in rats and rabbits at doses near the maximum tolerated dose and/or maternally toxic doses showed reproductive (embryotoxicity in rats, embryo resorption and foetotoxicity in rabbits) and developmental (decrease in pup growth and survival in rats) toxicity, but was not teratogenic and did not impair fertility. These findings were observed at clinically relevant exposures.
Erlotinib tested negative in conventional genotoxicity studies. Two-year carcinogenicity studies with erlotinib conducted in rats and mice were negative up to exposures exceeding human therapeutic exposure (up to 2-fold and 10-fold higher, respectively, based on Cmax and/or AUC).
A mild phototoxic skin reaction was observed in rats after UV irradiation.
Non-Small Cell Lung Cancer (NSCLC): Erlotinib tablets are indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor activating mutations (EGFR).
Erlotinib tablets are also indicated for the treatment of patients with locally advanced or metastatic NSCLC with EGFR activating mutations and stable disease after first-line chemotherapy.
Erlotinib tablets are also indicated for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. In patients with tumours without EGFR activating mutations, ERLONAT is indicated when other treatment options are not considered suitable.
When prescribing erlotinib tablets, 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 (see Pharmacology: Pharmacodynamics under Actions).
Pancreatic cancer: Erlotinib tablets in combination with gemcitabine is indicated for the treatment of patients with metastatic pancreatic cancer.
When prescribing erlotinib tablets, factors associated with prolonged survival should be taken into account (see Dosage & Administration and Pharmacology: Pharmacodynamics under Actions).
No survival advantage could be shown for patients with locally advanced disease.
Erlotinib tablets treatment should be supervised by a physician experienced in the use of anti-cancer therapies.
Patients with Non-Small Cell Lung Cancer: EGFR mutation testing should be performed in accordance with the approved indications (see Indications/Uses).
The recommended daily dose of Erlotinib tablets is 150 mg taken at least one hour before or two hours after the ingestion of food.
Patients with pancreatic cancer: The recommended daily dose of erlotinib tablets are 100 mg taken at least one hour before or two hours after the ingestion of food, in combination with gemcitabine (see the summary of product characteristics of gemcitabine for the pancreatic cancer indication). In patients who do not develop rash within the first 4-8 weeks of treatment, further erlotinib tablets treatment should be re-assessed (see Pharmacology: Pharmacodynamics under Actions).
When dose adjustment is necessary, the dose should be reduced in 50 mg steps (see Precautions).
Erlotinib tablets are available in strengths of 25 mg, 100 mg and 150 mg.
Concomitant use of CYP3A4 substrates and modulators may require dose adjustment (see Interactions).
Hepatic impairment: Erlotinib is eliminated by hepatic metabolism and biliary excretion. Although erlotinib exposure was similar in patients with moderately impaired hepatic function (Child-Pugh score 7-9) compared with patients with adequate hepatic function, caution should be used when administering erlotinib tablets to patients with hepatic impairment. Dose reduction or interruption of erlotinib tablets should be considered if severe adverse reactions occur. The safety and efficacy of erlotinib has not been studied in patients with severe hepatic dysfunction (AST/SGOT and ALT/SGPT >5x ULN). Use of erlotinib tablets in patients with severe hepatic dysfunction is not recommended (see Pharmacology: Pharmacokinetics under Actions).
Renal impairment: The safety and efficacy of erlotinib has not been studied in patients with renal impairment (serum creatinine concentration >1.5 times the upper normal limit). Based on pharmacokinetic data no dose adjustments appear necessary in patients with mild or moderate renal impairment (see Pharmacology: Pharmacokinetics under Actions). Use of erlotinib tablets in patients with severe renal impairment is not recommended.
Paediatric population: The safety and efficacy of erlotinib in the approved indications has not been established in patients under the age of 18 years. Use of erlotinib tablets in paediatric patients is not recommended.
Smokers: Cigarette smoking has been shown to reduce erlotinib exposure by 50-60%. The maximum tolerated dose of erlotinib tablets in NSCLC patients who currently smoke cigarettes was 300 mg. The 300 mg dose did not show improved efficacy in second line treatment after failure of chemotherapy compared to the recommended 150 mg dose in patients who continue to smoke cigarettes. Safety data were comparable between the 300 mg and 150 mg doses; however, there was a numerical increase in the incidence of rash, interstitial lung disease and diarrhoea, in patients receiving the higher dose of erlotinib. Current smokers should be advised to stop smoking (see Precautions, Interactions, Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Symptoms: Single oral doses of erlotinib tablets up to 1000 mg erlotinib in healthy subjects, and up to 1600 mg in cancer patients have been tolerated. Repeated twice daily doses of 200 mg in healthy subjects were poorly tolerated after only a few days of dosing. Based on the data from these studies, severe adverse reactions such as diarrhoea, rash and possibly increased activity of liver aminotransferases may occur above the recommended dose.
Management: In case of suspected overdose, erlotinib tablets should be withheld and symptomatic treatment initiated.
Hypersensitivity to erlotinib or to any of the excipients listed in Description.
Assessment of EGFR mutation status: When considering the use of erlotinib tablets as a first line or maintenance treatment for locally advanced or metastatic NSCLC, it is important that the EGFR mutation status of a patient is determined.
A validated, robust, reliable and sensitive test with a prespecified positivity threshold and demonstrated utility for the determination of EGFR mutation status, using either tumor DNA derived from a tissue sample or circulating free DNA (cfDNA) obtained from a blood (plasma) sample, should be performed according to local medical practice.
If a plasma-based cfDNA test is used and the result is negative for activating mutations, perform a tissue test wherever possible due to the potential for false negative results from a plasma-based test.
Smokers: Current smokers should be advised to stop smoking, as plasma concentrations of erlotinib in smokers as compared to non-smokers are reduced. The degree of reduction is likely to be clinically significant (see Dosage & Administration, Interactions, Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Interstitial Lung Disease: Cases of interstitial lung disease (ILD)-like events, including fatalities, have been reported uncommonly in patients receiving erlotinib tablets for treatment of non-small cell lung cancer (NSCLC), pancreatic cancer or other advanced solid tumours. In the pivotal study BR.21 in NSCLC, the incidence of ILD (0.8%) was the same in both the placebo and erlotinib tablets groups. In a meta-analysis of NSCLC randomized controlled clinical trials (excluding phase I and single-arm phase II studies due to lack of control groups), the incidence of ILD-like events was 0.9% on Erlotinib tablets compared to 0.4% in patients in the control arms. In the pancreatic cancer study in combination with gemcitabine, the incidence of ILD-like events was 2.5% in the Erlotinib tablets plus gemcitabine group versus 0.4% in the placebo plus gemcitabine treated group. Reported diagnoses in patients suspected of having ILD-like events included pneumonitis, radiation pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, pulmonary fibrosis, Acute Respiratory Distress Syndrome (ARDS), alveolitis, and lung infiltration. Symptoms started from a few days to several months after initiating Erlotinib tablets therapy. Confounding or contributing factors such as concomitant or prior chemotherapy, prior radiotherapy, pre-existing parenchymal lung disease, metastatic lung disease, or pulmonary infections were frequent. A higher incidence of ILD (approximately 5% with a mortality rate of 1.5%) is seen among patients in studies conducted in Japan.
In patients who develop acute onset of new and/or progressive unexplained pulmonary symptoms such as dyspnoea, cough and fever, Erlotinib tablets therapy should be interrupted pending diagnostic evaluation. Patients treated concurrently with erlotinib and gemcitabine should be monitored carefully for the possibility to develop ILD-like toxicity. If ILD is diagnosed, Erlotinib tablets should be discontinued and appropriate treatment initiated as necessary (see Adverse Reactions).
Diarrhoea, dehydration, electrolyte imbalance and renal failure: Diarrhoea (including very rare cases with a fatal outcome) has occurred in approximately 50% of patients on erlotinib tablets and moderate or severe diarrhoea should be treated with e.g. loperamide. In some cases dose reduction may be necessary. In the clinical studies doses were reduced by 50 mg steps. Dose reductions by 25 mg steps have not been investigated. In the event of severe or persistent diarrhoea, nausea, anorexia, or vomiting associated with dehydration, erlotinib tablets therapy should be interrupted and appropriate measures should be taken to treat the dehydration (see Adverse Reactions). There have been rare reports of hypokalaemia and renal failure (including fatalities). Some cases were secondary to severe dehydration due to diarrhoea, vomiting and/or anorexia, while others were confounded by concomitant chemotherapy. In more severe or persistent cases of diarrhoea, or cases leading to dehydration, particularly in groups of patients with aggravating risk factors (especially concomitant chemotherapy and other medications, symptoms or diseases or other predisposing conditions including advanced age), erlotinib tablets therapy should be interrupted and appropriate measures should be taken to intensively rehydrate the patients intravenously. In addition, renal function and serum electrolytes including potassium should be monitored in patients at risk of dehydration.
Hepatitis, hepatic failure: Rare cases of hepatic failure (including fatalities) have been reported during use of erlotinib tablets. Confounding factors have included pre-existing liver disease or concomitant hepatotoxic medications. Therefore, in such patients, periodic liver function testing should be considered. Erlotinib tablets dosing should be interrupted if changes in liver function are severe (see Adverse Reactions). Erlotinib tablets is not recommended for use in patients with severe hepatic dysfunction.
Gastrointestinal perforation: Patients receiving erlotinib tablets are at increased risk of developing gastrointestinal perforation, which was observed uncommonly (including some cases with a fatal outcome). Patients receiving concomitant anti-angiogenic agents, corticosteroids, NSAIDs, and/or taxane based chemotherapy, or who have prior history of peptic ulceration or diverticular disease are at increased risk. Erlotinib tablets should be permanently discontinued in patients who develop gastrointestinal perforation (see Adverse Reactions).
Bullous and exfoliative skin disorders: Bullous, blistering and exfoliative skin conditions have been reported, including very rare cases suggestive of Stevens-Johnson syndrome/Toxic epidermal necrolysis, which in some cases were fatal (see Adverse Reactions). Erlotinib tablets treatment should be interrupted or discontinued if the patient develops severe bullous, blistering or exfoliating conditions. Patients with bullous and exfoliative skin disorders should be tested for skin infection and treated according to local management guidelines.
Ocular disorders: Patients presenting with signs and symptoms suggestive of keratitis such as acute or worsening: eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye should be referred promptly to an ophthalmology specialist. If a diagnosis of ulcerative keratitis is confirmed, treatment with erlotinib tablets should be interrupted or discontinued. If keratitis is diagnosed, the benefits and risks of continuing treatment should be carefully considered. Erlotinib tablets should be used with caution in patients with a history of keratitis, ulcerative keratitis or severe dry eye. Contact lens use is also a risk factor for keratitis and ulceration. Very rare cases of corneal perforation or ulceration have been reported during use of erlotinib tablets (see Adverse Reactions).
Interactions with other medicinal products: Potent inducers of CYP3A4 may reduce the efficacy of erlotinib whereas potent inhibitors of CYP3A4 may lead to increased toxicity. Concomitant treatment with these types of agents should be avoided (see Interactions).
Other forms of interactions: Erlotinib is characterised by a decrease in solubility at pH above 5. Medicinal products that alter the pH of the upper Gastro-Intestinal (GI) tract, like proton pump inhibitors, H2 antagonists and antacids, may alter the solubility of erlotinib and hence its bioavailability. Increasing the dose of erlotinib tablets when co-administered with such agents is not likely to compensate for the loss of exposure. Combination of erlotinib with proton pump inhibitors should be avoided. The effects of concomitant administration of erlotinib with H2 antagonists and antacids are unknown; however, reduced bioavailability is likely. Therefore, concomitant administration of these combinations should be avoided (see Interactions). If the use of antacids is considered necessary during treatment with erlotinib tablets, they should be taken at least 4 hours before or 2 hours after the daily dose of erlotinib tablets.
The tablets contain lactose and should not be administered to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed; however erlotinib is not associated with impairment of mental ability.
Pregnancy: There are no adequate data for the use of erlotinib in pregnant women. Studies in animals have shown no evidence of teratogenicity or abnormal parturition. However, an adverse effect on the pregnancy cannot be excluded as rat and rabbit studies have shown increased embryo/foetal lethality (see Pharmacology: Toxicology: Preclinical safety data under Actions). The potential risk for humans is unknown.
Women of childbearing potential: Women of childbearing potential must be advised to avoid pregnancy while on erlotinib tablets. Adequate contraceptive methods should be used during therapy, and for at least 2 weeks after completing therapy. Treatment should only be continued in pregnant women if the potential benefit to the mother outweighs the risk to the foetus.
Breast-feeding: It is not known whether erlotinib tablets is excreted in human milk. No studies have been conducted to assess the impact of erlotinib tablets on milk production or its presence in breast milk. As the potential for harm to the nursing infant is unknown, mothers should be advised against breast-feeding while receiving erlotinib tablets and for at least 2 weeks after the final dose.
Fertility: Studies in animals have shown no evidence of impaired fertility. However, an adverse effect on the fertility cannot be excluded as animal studies have shown effects on reproductive parameters (see Pharmacology: Toxicology: Preclinical safety data under Actions). The potential risk for humans is unknown.
Adverse effect occurring in 10% or more of patients receiving erlotinib monotherapy in one clinical study and with an incidence at least 3% more frequent than with placebo included rash, diarrhea, anorexia, fatigue, dyspnea, cough, nausea, infection, vomiting, stomatitis, pruritus, dry skin, conjunctivitis, keratoconjunctivitis sicca, and abdominal pain.
The adverse effects occurring most frequently (incidence greater than 30%) in patients receiving erlotinib and gemcitabine for pancreatic cancer in a randomized trial included fatigue, rash, nausea, anorexia, diarrhea, abdominal pain, vomiting, decreased weight, infection, edema, pyrexia, and constipation.
Interaction studies have only been performed in adults.
Erlotinib and other CYP substrates: Erlotinib is a potent inhibitor of CYP1A1, and a moderate inhibitor of CYP3A4 and CYP2C8, as well as a strong inhibitor of glucuronidation by UGT1A1 in vitro.
The physiological relevance of the strong inhibition of CYP1A1 is unknown due to the very limited expression of CYP1A1 in human tissues.
When erlotinib was co-administered with ciprofloxacin, a moderate CYP1A2 inhibitor, the erlotinib exposure [AUC] increased significantly by 39%, while no statistically significant change in Cmax was found. Similarly, the exposure to the active metabolite increased by about 60% and 48% for AUC and Cmax, respectively. The clinical relevance of this increase has not been established. Caution should be exercised when ciprofloxacin or potent CYP1A2 inhibitors (e.g. fluvoxamine) are combined with erlotinib. If adverse reactions related to erlotinib are observed, the dose of erlotinib may be reduced.
Pre-treatment or co-administration of erlotinib tablets did not alter the clearance of the prototypical CYP3A4 substrates, midazolam and erythromycin, but did appear to decrease the oral bioavailability of midazolam by up to 24%. In another clinical study, erlotinib was shown not to affect pharmacokinetics of the concomitantly administered CYP3A4/2C8 substrate paclitaxel. Significant interactions with the clearance of other CYP3A4 substrates are therefore unlikely.
The inhibition of glucuronidation may cause interactions with medicinal products which are substrates of UGT1A1 and exclusively cleared by this pathway. Patients with low expression levels of UGT1A1 or genetic glucuronidation disorders (e.g. Gilbert's disease) may exhibit increased serum concentrations of bilirubin and must be treated with caution.
Erlotinib is metabolised in the liver by the hepatic cytochromes in humans, primarily CYP3A4 and to a lesser extent by CYP1A2. Extrahepatic metabolism by CYP3A4 in intestine, CYP1A1 in lung, and CYP1B1 in tumour tissue also potentially contribute to the metabolic clearance of erlotinib. Potential interactions may occur with active substances which are metabolised by, or are inhibitors or inducers of, these enzymes.
Potent inhibitors of CYP3A4 activity decrease erlotinib metabolism and increase erlotinib plasma concentrations. In a clinical study, the concomitant use of erlotinib with ketoconazole (200 mg orally twice daily for 5 days), a potent CYP3A4 inhibitor, resulted in an increase of erlotinib exposure (86% of AUC and 69% of Cmax). Therefore, caution should be used when erlotinib is combined with a potent CYP3A4 inhibitor, e.g. azole antifungals (i.e. ketoconazole, itraconazole, voriconazole), protease inhibitors, erythromycin or clarithromycin. If necessary the dose of erlotinib should be reduced, particularly if toxicity is observed.
Potent inducers of CYP3A4 activity increase erlotinib metabolism and significantly decrease erlotinib plasma concentrations. In a clinical study, the concomitant use of erlotinib and rifampicin (600 mg orally once daily for 7 days), a potent CYP3A4 inducer, resulted in a 69% decrease in the median erlotinib AUC. Co-administration of rifampicin with a single 450 mg dose of erlotinib tablets resulted in a mean erlotinib exposure (AUC) of 57.5% of that after a single 150 mg erlotinib tablets dose in the absence of rifampicin treatment. Co-administration of erlotinib tablets with CYP3A4 inducers should therefore be avoided. For patients who require concomitant treatment with erlotinib tablets and a potent CYP3A4 inducer such as rifampicin an increase in dose to 300 mg should be considered while their safety (including renal and liver functions and serum electrolytes) is closely monitored, and if well tolerated for more than 2 weeks, further increase to 450 mg could be considered with close safety monitoring. Reduced exposure may also occur with other inducers e.g. phenytoin, carbamazepine, barbiturates or St. John's Wort (Hypericum perforatum). Caution should be observed when these active substances are combined with erlotinib. Alternate treatments lacking potent CYP3A4 inducing activity should be considered when possible.
Erlotinib and coumarin-derived anticoagulants: Interaction with coumarin-derived anticoagulants including warfarin leading to increased International Normalized Ratio (INR) and bleeding events, which in some cases were fatal, have been reported in patients receiving erlotinib tablets. Patients taking coumarin-derived anticoagulants should be monitored regularly for any changes in prothrombin time or INR.
Erlotinib and statins: The combination of erlotinib tablets and a statin may increase the potential for statin-induced myopathy, including rhabdomyolysis, which was observed rarely.
Erlotinib and smokers: Results of a pharmacokinetic interaction study indicated a significant 2.8-, 1.5- and 9-fold reduced AUCinf, Cmax and plasma concentration at 24 hours, respectively, after administration of erlotinib tablets in smokers as compared to non-smokers. Therefore, patients who are still smoking should be encouraged to stop smoking as early as possible before initiation of treatment with erlotinib tablets, as plasma erlotinib concentrations are reduced otherwise. Based on the data from the CURRENTS study, no evidence was seen for any benefit of a higher erlotinib dose of 300 mg when compared with the recommended dose of 150 mg in active smokers. Safety data were comparable between the 300 mg and 150 mg doses; however, there was a numerical increase in the incidence of rash, interstitial lung disease and diarrhoea, in patients receiving the higher dose of erlotinib (see Dosage & Administration, Precautions, Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Erlotinib and P-glycoprotein inhibitors: Erlotinib is a substrate for the P-glycoprotein active substance transporter. Concomitant administration of inhibitors of Pgp, e.g. cyclosporine and verapamil, may lead to altered distribution and/or altered elimination of erlotinib. The consequences of this interaction for e.g. CNS toxicity have not been established. Caution should be exercised in such situations.
Erlotinib and medicinal products altering pH: Erlotinib is characterised by a decrease in solubility at pH above 5. Medicinal products that alter the pH of the upper Gastro-Intestinal (GI) tract may alter the solubility of erlotinib and hence its bioavailability. Co-administration of erlotinib with omeprazole, a proton pump inhibitor (PPI), decreased the erlotinib exposure [AUC] and maximum concentration [Cmax] by 46% and 61%, respectively. There was no change to Tmax or half-life. Concomitant administration of erlotinib tablets with 300 mg ranitidine, an H2-receptor antagonist, decreased erlotinib exposure [AUC] and maximum concentrations [Cmax] by 33% and 54%, respectively. Increasing the dose of erlotinib tablets when coadministered with such agents is not likely to compensate for this loss of exposure. However, when erlotinib tablets was dosed in a staggered manner 2 hours before or 10 hours after ranitidine 150 mg b.i.d., erlotinib exposure [AUC] and maximum concentrations [Cmax] decreased only by 15% and 17%, respectively. The effect of antacids on the absorption of erlotinib has not been investigated but absorption may be impaired, leading to lower plasma levels. In summary, the combination of erlotinib with proton pump inhibitors should be avoided. If the use of antacids is considered necessary during treatment with erlotinib tablets, they should be taken at least 4 hours before or 2 hours after the daily dose of erlotinib tablets. If the use of ranitidine is considered, it should be used in a staggered manner; i.e. erlotinib tablets must be taken at least 2 hours before or 10 hours after ranitidine dosing.
Erlotinib and Gemcitabine: In a Phase Ib study, there were no significant effects of gemcitabine on the pharmacokinetics of erlotinib nor were there significant effects of erlotinib on the pharmacokinetics of gemcitabine.
Erlotinib and Carboplatin/Paclitaxel: Erlotinib increases platinum concentrations. In a clinical study, the concomitant use of erlotinib with carboplatin and paclitaxel led to an increase of total platinum AUC0-48 of 10.6%. Although statistically significant, the magnitude of this difference is not considered to be clinically relevant. In clinical practice, there may be other co-factors leading to an increased exposure to carboplatin like renal impairment. There were no significant effects of carboplatin or paclitaxel on the pharmacokinetics of erlotinib.
Erlotinib and Capecitabine: Capecitabine may increase erlotinib concentrations. When erlotinib was given in combination with capecitabine, there was a statistically significant increase in erlotinib AUC and a borderline increase in Cmax when compared with values observed in another study in which erlotinib was given as single agent. There were no significant effects of erlotinib on the pharmacokinetics of capecitabine.
Erlotinib and proteasome inhibitors: Due to the working mechanism, proteasome inhibitors including bortezomib may be expected to influence the effect of EGFR inhibitors including erlotinib. Such influence is supported by limited clinical data and preclinical studies showing EGFR degradation through the proteasome.
Incompatibilities: Not applicable.
Special precautions for disposal and other handling: No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Do not store above 30°C. Protect from moisture.
Shelf life: 36 months.
L01EB02 - erlotinib ; Belongs to the class of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Used in the treatment of cancer.
Erlonat FC tab 150 mg
3 × 10's
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