Members Login
Medical NewsEPG Search
Frequent Searches:
Browse Other Languages
Spanish Drug Data (España)
German Drug Data (Deutsch)
Norwegian Drug Data (Norge)
Netherlands Drug Data (Nederlands)
Swedish Drug Data (Sverige)
German Drug Data (Deutsch)
Norwegian Drug Data (Norge)
Netherlands Drug Data (Nederlands)
Swedish Drug Data (Sverige)
YouTube - Featured Content
Want to submit or suggest content for the epgonline.org YouTube Clinical channel?
Contact us here
epgonline.org is not responsible for content on any 3rd party website
Are you a Doctor or Healthcare Professional? Authorise Viewing
Please register to access disease diagnosis, patient management, physician tools.
By viewing the content of this web page you are both confirming your status as a healthcare professional and agreeing to our terms of use.
Change language
Current language database:
United Kingdom
Medicine information : TARCEVA Film-Coated Tablets
| Drug class description : | Antineoplastic Agent |
| Generic Name : | Erlotinib Hydrochloride |
| Drug description : | Filmcoated tablet - White to yellowish, round, biconvex tablets with 'Tarceva 25' and logo printed in brownish yellow on one side. White to yellowish, round, biconvex tablets with 'Tarceva 100' and logo printed in grey on one side. White to yellowish, round, biconvex tablets with 'Tarceva 150' and logo printed in brown on one side. |
| Presentation : | One filmcoated tablet of each strength contains 25 mg, 100 mg or 150 mg erlotinib (as erlotinib hydrochloride). |
| Indications : | Non-small cell lung cancer (NSCLC): Tarceva 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. 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 EGFR- negative tumours. Pancreatic cancer: Tarceva 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 (See Adult Dosage). No survival advantage could be shown for patients with locally advanced disease. |
| Adult Dosage : | Tarceva treatment should be supervised by a physician experienced in the use of anticancer therapies. Non-small cell lung cancer: The recommended daily dose of Tarceva is 150 mg taken at least one hour before or two hours after the ingestion of food. Pancreatic cancer: The recommended daily dose of Tarceva is 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 Tarceva treatment should be re-assessed. When dose adjustment is necessary, reduce in 50 mg steps (See Special Precautions). Tarceva is 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. The safety and efficacy of erlotinib has not been studied in patients with hepatic impairment. Therefore caution should be exercised when administering Tarceva to patients with hepatic impairment. Use of Tarceva in patients with severe hepatic impairment is not recommended. 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. Use of Tarceva in patients with severe renal impairment is not recommended. |
| Child Dosage : | The safety and efficacy of erlotinib has not been studied in patients under the age of 18 years. Use of Tarceva in paediatric patients is not recommended. |
| Elderly Dosage : | See Adult Dosage |
| Contra Indications : | Severe hypersensitivity to erlotinib or to any of the excipients. |
| Special Precautions : | 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). 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 Interactions). Cases of interstitial lung disease (ILD)-like events, including fatalities, have been reported uncommonly in patients receiving Tarceva 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 Tarceva groups. In the pancreatic cancer study in combination with gemcitabine, the incidence of ILD-like events was 2.5 % in the Tarceva plus gemcitabine group versus 0.4 % in the placebo plus gemcitabine treated group. The overall incidence in Tarceva-treated patients from all studies (including uncontrolled studies and studies with concurrent chemotherapy) is approximately 0.6 % compared to 0.2 % in patients on placebo. 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), and lung infiltration. Symptoms started from a few days to several months after initiating Tarceva 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. In patients who develop acute onset of new and/or progressive unexplained pulmonary symptoms such as dyspnoea, cough and fever, Tarceva 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, Tarceva should be discontinued and appropriate treatment initiated as necessary (See Adverse Reactions). Diarrhoea has occurred in approximately 50 % of patients on Tarceva 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, Tarceva 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 (concomitant medications, symptoms or diseases or other predisposing conditions including advanced age), Tarceva 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. Rare cases of hepatic failure (including fatalities) have been reported during use of Tarceva. Confounding factors have included pre-existing liver disease or concomitant hepatotoxic medications. Therefore, in such patients, periodic liver function testing should be considered. Tarceva dosing should be interrupted if changes in liver function are severe (See Adverse Reactions). 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. Erlotinib is characterised by a decrease in solubility at pH above 5. Drugs that alter the pH of the upper GI tract, like proton pump inhibitors, H2 antagonists and antacids, may alter the solubility of erlotinib and hence its bioavailability. Increasing the dose of Tarceva when coadministered 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 Tarceva, they should be taken at least 4 hours before or 2 hours after the daily dose of Tarceva. |
| Interactions : | 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. The effects of CYP1A2 inhibitors on the pharmacokinetics of erlotinib have not been investigated and caution should be exercised when these inhibitors are combined with erlotinib. No clinical interaction study with a CYP3A4 substrate has been performed as yet. Based on in vitro data, combination of erlotinib with CYP3A4 substrates should be conducted with caution. If such a combination is considered necessary a close clinical monitoring should be performed. In a clinical study, erlotinib was shown not to affect pharmacokinetics of the concomitantly administered CYP3A4/2C8 substrate paclitaxel. 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. The clinical relevance of this observation is unclear, but efficacy may be reduced. Reduced exposure may also occur with other inducers e.g. phenytoin, carbamazepine, barbiturates or St. Johns 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. International Normalised Ratio (INR) elevations, and bleeding events including gastrointestinal bleeding have been reported in clinical studies, some associated with concomitant warfarin administration (See Adverse Reactions) and some with concomitant NSAID administration. Patients taking warfarin or other coumarinderivative anticoagulants should be monitored regularly for changes in prothrombin time or INR. Based on the results of the population pharmacokinetic study, patients who are still smoking should be encouraged to stop smoking while taking Tarceva, as plasma concentrations could be reduced otherwise. 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 has not been established. Caution should be exercised in such situations. Erlotinib is characterised by a decrease in solubility at pH above 5. The effect of antacids, proton pump inhibitors and H2 antagonists on the absorption of erlotinib have not been investigated but absorption may be impaired, leading to lower plasma levels. Caution should be exercised when these medicinal products are combined with erlotinib. Pregnancy and lactation There are no studies in pregnant women using erlotinib. Studies in animals have shown some reproductive toxicity. The potential risk for humans is unknown. Women of childbearing potential must be advised to avoid pregnancy while on Tarceva. 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. It is not known whether erlotinib is excreted in human milk. Because of the potential harm to the infant, mothers should be advised against breastfeeding while receiving Tarceva. |
| Adverse Reactions : | Non-small cell lung cancer (Tarceva administered as single agent in study BR.21): Rash (75 %) and diarrhoea (54 %) were the most commonly reported adverse drug reactions (ADRs). Most were Grade 1/2 in severity and manageable without intervention. Grade 3/4 rash and diarrhoea occurred in 9 % and 6 %, respectively in Tarceva-treated patients and each resulted in study discontinuation in 1 % of patients. Dose reduction for rash and diarrhoea was needed in 6 % and 1 % of patients, respectively. In study BR.21, the median time to onset of rash was 8 days, and the median time to onset of diarrhoea was 12 days. Adverse events occurring more frequently (3 %) in Tarceva-treated patients than in the placebo group in the pivotal study BR.21, and in at least 10 % of patients in the Tarceva group, are summarised by National Cancer Institute-Common Toxicity Criteria (NCI-CTC). Pancreatic cancer (Tarceva administered concurrently with gemcitabine in study PA.3): The most common adverse reactions in pivotal study PA.3 in pancreatic cancer patients receiving Tarceva 100 mg plus gemcitabine were fatigue, rash and diarrhoea. In the Tarceva plus gemcitabine arm, Grade 3/4 rash and diarrhoea were each reported in 5 % of patients. The median time to onset of rash and diarrhoea was 10 days and 15 days, respectively. Rash and diarrhoea each resulted in dose reductions in 2 % of patients, and resulted in study discontinuation in up to 1 % of patients receiving Tarceva plus gemcitabine. Adverse events occurring more frequently (3 %) in Tarceva 100 mg plus gemcitabine-treated patients than in the placebo plus gemcitabine group in the pivotal study PA.3, and in at least 10 % of patients in the Tarceva 100 mg plus gemcitabine group, are summarised by National Cancer Institute-Common Toxicity Criteria (NCI-CTC). Other Observations: Safety evaluation of Tarceva is based on the data from 759 patients treated with at least one 150 mg dose of Tarceva monotherapy during Phase III NSCLC study BR.21, Phase II NSCLC study A248-1007, and three Phase II studies in populations other than NSCLC: 248-101 (ovarian cancer), A248-1003 (head and neck cancer), and OSI2288g (metastatic breast cancer) and the 285 patients who received Tarceva 100 or 150 mg plus gemcitabine in the phase III pancreatic cancer study PA.3. The following terms are used to rank the undesirable effects by frequency: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1/1000); very rare (<1/10,000) including isolated reports. The following adverse reactions have been observed in patients who received Tarceva administered as single agent and patients who received Tarceva concurrently with chemotherapy. Very common ADR's are presented above, ADR's in other frequency categories are summarised below. Gastrointestinal disorders: Common - Gastrointestinal bleeding. In clinical studies, some cases have been associated with concomitant warfarin administration (See Interactions) and some with concomitant NSAID administration. Skin and subcutaneous tissue orders: Common - Alopecia. Common (in PA.3) - Dry skin. Hepato-biliary disorders: Very common (in PA.3) Common (in BR.21): Liver function test abnormalities (including increased alanine aminotransferase [ALT], aspartate aminotransferase [AST], bilirubin). These were mainly mild or moderate in severity, transient in nature or associated with liver metastases. Rare: Rare cases of hepatic failure (including fatalities) have been reported during use of Tarceva. Confounding factors have included pre-existing liver disease or concomitant hepatotoxic medications (See Special Precautions). Eye disorders: Common - Keratitis. One isolated case of corneal ulceration was reported in one patient receiving Tarceva with concurrent chemotherapy, as a complication of mucocutaneous inflammation. Common: Conjunctivitis in study PA.3 Respiratory, thoracic and mediastinal disorders: Common - Epistaxis. Uncommon - Serious interstitial lung disease (ILD), including fatalities, in patients receiving Tarceva for treatment of NSCLC or other advanced solid tumours (See Special Precautions). |
| Manufacturer : | Roche |
| Drug Availability : | (POM) |
Free registration to access disease diagnosis, patient management, physician tools.
Only registered users have access to the full EPG Online Knowledge Base including drug search tools, interactive disease Knowledge Centres via the EPG Knowledge Library - with clinical and evidence based physician and research tools, MiMedia (build your own clinical media collection with everything from key opinion leader essays to mode of action videos and other multi-media content), the EPG Survey panel, health news updates and much much more.
Already Registered?
Please log-in now using our member login box.
Not a member?
Don't worry, registration is quick and FREE! We welcome all Healthcare professionals, doctors, nurses and medical students.
Register today to have full access to a wealth of drug data, educational and evidence based interactive guides across all major therapeutic areas, disease management, and clinical tools.
As a practicing Healthcare professional, you can also opt-in to join our market research panel – www.epgsurvey.com – and get paid for sharing your expert clinical opinions!
REGISTER today it only takes a minute! and it's FREE
Having problems?
Use our forgotten password facility or email us at: contact@epgonline.org