Erlocip 25mg, 100mg, 150mg FC tablet

Non-Small Cell Lung Cancer (NSCLC) ERLOCIP is indicated for the treatment of patients with locally advanced or metastatic non- small cell lung cancer with EGFR activating mutation after failure of at least one prior chemotherapy regimen. ERLOCIP was not effective after platinum-based therapy that included gemcitabine. ERLOCIP monotherapy is indicated for the maintenance treatment of patients having received first-line platinum-based (other than gemcitabine + cisplatin) doublets chemotherapy for locally advanced or metastatic NSCLC. No survival benefit or other clinically relevant effects of the treatment have been demonstrated in patients with EGFR- negative tumours. Bronchial Adenocarcinoma ERLOCIP is indicated for the first-line treatment of patients with locally advanced or metastatic (stage 4) bronchial adenocarcinoma whose tumours have demonstrated EGFR activating mutations and who have never smoked and had ECOG performance status of 0 u2013 1. When prescribing ERLOCIP, 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 ERLOCIP in combination with gemcitabine is indicated for the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.

Posology ERLOCIP therapy should be supervised by a medical practitioner experienced in anticancer therapies. Concomitant use of CYP3A4 substrates and modulators may require dose adjustment (see section 4.5). Where dose adjustment is necessary, reduce in 50 mg steps. Non-Small Cell Lung Cancer and Bronchial Adenocarcinoma: EGFR mutation testing should be performed prior to initiation of ERLOCIP therapy in chemo- naive patients with advanced or metastatic NSCLC and bronchial adenocarcinoma. The recommended dose is 150 mg daily taken at least 1 hour before or two hours after the ingestion of food. Where dose adjustment is necessary, reduce in 50 mg steps. Pancreatic Cancer: The recommended dose of ERLOCIP is one 100 mg tablet daily taken at least one hour before or two hours after ingestion of food. in combination with gemcitabine (see gemcitabine professional information for pancreatic cancer indication). Hepatic Impairment: ERLOCIP is eliminated by hepatic metabolism and biliary excretion. Although erlotinib exposure was similar in patients with moderately impaired hepatic function (Child-Pugh score 7 to 9) compared with patients with adequate hepatic function, caution should be used when administering ERLOCIP to patients with hepatic impairment (see section 5.2). ERLOCIP should not be used in patients with severe hepatic dysfunction (AST/SGOT and ALT/SGPT > 5 x ULN). Dose reduction or interruption of ERLOCIP should be considered if severe adverse reactions occur. Safety and efficacy have not been studied in patients with severe hepatic dysfunction. Renal Impairment: The safety and efficacy of ERLOCIP have not been established in patients with renal impairment (see section 5.2). ERLOCIP must not be used in patients with severe renal dysfunction. Smokers: Cigarette smoking has been shown to reduce erlotinib exposure by 50 - 60 %. The maximum tolerated dose of ERLOTINIB in NSCLC and bronchial adenocarcinoma 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. Paediatric population: Safety and efficacy have not been established in patients under the age of 18. Method of administration: Oral use.

Severe hypersensitivity to erlotinib or to any of the excipients listed in section 6.1.

Interstitial Lung Disease: Patients who are using ERLOCIP in the treatment of non-small cell lung cancer (NSCLC), pancreatic cancer or those with advanced solid tumours have less frequently reported cases of interstitial lung disease (ILD), including that of fatalities. In the pivotal study BR.21 in NSCLC, the incidence of ILD-like events was (0,8 %) the same in both the placebo and the erlotinib groups. In the pancreatic cancer study in combination with gemcitabine, the incidence of ILD-like events was 2,5 % in the erlotinib plus gemcitabine group versus 0,4 % in the placebo plus gemcitabine- treated group. The overall incidence in erlotinib-treated patients from all studies (including uncontrolled studies and studies with concurrent chemotherapy) is approximately 0,6 %. Some examples of reported diagnosis in patients suspected of having ILD included pneumonitis, radiation pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, pulmonary fibrosis, Acute Respiratory Distress Syndrome and lung infiltration. These ILD-like events started from a few days to several months after initiating erlotinib therapy. Most of the cases were associated with confounding or contributing factors such as concomitant or prior chemotherapy, prior radiotherapy, pre-existing parenchymal lung disease, metastatic lung disease or pulmonary infections. In patients who develop dyspnoea, cough, fever or other acute onsets of progressive pulmonary symptoms while on ERLOCIP, therapy should stop and undergo diagnostic evaluation. Patients treated concurrently with ERLOCIP and gemcitabine should be monitored carefully for the possibility to develop ILD-like toxicity. If ILD is diagnosed, ERLOCIP should be discontinued and the appropriate treatment administered (see Section 4.8) Diarrhoea, Dehydration, Electrolyte Imbalance and Renal Failure: Diarrhoea (including very rare cases with a fatal outcome) has occurred in approximately 50 % of patients on ERLOCIP and moderate to severe diarrhoea should be treated with e.g. loperamide. In some cases, dose reduction may be necessary. With regards to dehydration associated with severe or persistent vomiting, diarrhoea, anorexia or vomiting, ERLOCIP therapy should be interrupted, and dehydration should be appropriately treated. Appropriate measures should be taken to treat the dehydration (see Section 4.8.) Patients who are on concomitant chemotherapy present with a fatal risk of hypokalaemia and renal failure secondary to that of dehydration. In more severe or persistent cases of diarrhoea, or cases leading to dehydration, particularly in patients with aggravating risk factors (concomitant medicines, symptoms or diseases or other predisposing conditions including advanced age), ERLOCIP 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. Hepatitis, hepatic failure: Less frequent cases of hepatic failure including that of fatalities have been found during usage of ERLOCIP. Other compounding factors include pre-existing liver disease or concomitant hepatoxic medicine and therefore liver function tests should be considered. Therapy should be interrupted if changes in liver function are severe (see Section 4.8.) . ERLOCIP is not recommended for use in patients with severe hepatic dysfunction. 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 section 4.5). Gastrointestinal perforation Patients receiving ERLOCIP are at an increased risk of developing gastrointestinal perforation, which was observed uncommonly (including some cases with a fatal outcome). Patients receiving concomitant anti-angiogenic medicines, corticosteroids, Non-steroidal Anti-inflammatory Drugs (NSAIDs), and/or taxane based chemotherapy, or who have prior history of peptic ulceration or diverticular disease are at increased risk. ERLOCIP should be permanently discontinued in patients who develop gastrointestinal perforation (see section 4.8). 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 ERLOCIP should be interrupted or discontinued. If keratitis is diagnosed, the benefits and risks of continuing treatment should be carefully considered. ERLOCIP 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. Cases of corneal perforation or ulceration have been reported during use of ERLOCIP ( see section 4.8 ). Other ocular disorders including abnormal eyelash growth, keratoconjunctivitis sicca or keratitis have been observed with erlotinib treatment which are also risk factors for corneal perforation/ulceration. ERLOCIP therapy should be interrupted or discontinued if patients present with acute/worsening ocular disorders such as eye pain. Bullous and exfoliative skin disorders Bullous, blistering and exfoliative skin conditions have been reported, including cases suggestive of Stevens-Johnson syndrome/Toxic epidermal necrolysis, which in some cases were fatal (see section 4.8). ERLOCIP 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. For patients who are exposed to sun, protective clothing, and / or use of sunscreen (e.g. mineral containing) may be advisable. 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 sections 4.2, 4.5 and 5.2).

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 medicines should be avoided ( see section 4.5 ). Other forms of interactions: Erlotinib is characterised by a decrease in solubility above 5. Medicines that alter pH of the upper gastrointestinal (GI) tract, like proton pump inhibitors, H 2 antagonists and antacids, may alter the solubility of erlotinib and hence its bioavailability. Increasing the dose of ERLOCIP when co-administered with such medicines 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 H 2 antagonists and antacids are unknown; however, reduced bioavailability is likely. Therefore, concomitant administration of these combinations should be avoided (see section 4.5). If the use of antacids is considered necessary during treatment with ERLOCIP, they should be taken at least 4 hours before or 2 hours after the daily dose of ERLOCIP. Excipients: ERLOCIP tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take ERLOCIP.

Women who are pregnant and/or breastfeeding should not take ERLOCIP. Pregnancy: There is no significant data that supports the safe use of ERLOCIP in women that are pregnant. Animal studies have concluded an increase in foetal and embryo lethality. Women of Childbearing Potential Women of childbearing age should avoid pregnancy whilst on ERLOCIP treatment. Contraceptive methods should be implemented during treatment and two weeks after ERLOCIP treatment is completed. Breastfeeding: It is unknown as to whether erlotinib is excreted in breast milk or not. It is recommended that mothers should not breastfeed while on ERLOCIP therapy due to potential harm to the infant. Fertility: The potential for human risk is unknown even though animal studies have shown no risk on impaired fertility. However, adverse reactions cannot be ruled out.

ERLOCIP commonly causes keratitis of the eye and uncommonly causes corneal ulceration which may impair vision and hence affect the ability to drive and use machines. ERLOCIP is not associated with impairment of mental ability.

System Organ Class Frequent Less frequent Infections and infestations Infection 1 Metabolism and nutrition disorders Anorexia, decreased weight Psychiatric disorders Depression Nervous system disorders Headache, neuropathy Eye disorders Keratitis, keratoconjunctivitis sicca, conjunctivitis Eyelash changes (including in-growing eyelashes, excessive growth and thickening of the eyelashes), corneal ulcerations and perforations 2 , uveitis Respiratory, thoracic and mediastinal disorders Epistaxis, dyspnoea, cough Serious interstitial lung disease (ILD), including fatalities Gastrointestinal dissorders Diarrhoea 3 , nausea, vomiting, stomatitis, abdominal pain, dyspepsia, flatulence. Gastrointestinal perforations, including fatalities System Organ Class Frequent Less frequent Gastrointestinal bleeding4, including fatalities. Hepato-biliary disorders Liver function test abnormalities5 (including increased alanine aminotransferase [ALT], aspartate aminotransferase [AST], bilirubin) Cases of hepatic failure (including fatalities) 6 Skin and subcutaneous tissue disorders Alopecia, paronychia, dry skin, skin fissures, pruritus, rash7 (all grades). Acne, dermatitis acneiform and folliculitis 8 . Hirsutism, eyebrow changes and brittle and loose nails. Mild skin reactions such as hyperpigmentation. Bullous, blistering and exfoliative skin conditions including cases suggestive of Stevens-Johnson syndrome/Toxic epidermal necrolysis, which may be fatal. General disorders and administration site conditions Fatigue, pyrexia, rigors 1 Severe infections, with or without neutropenia, have included pneumonia, sepsis, and cellulitis. 2 Corneal ulcerations and perforations have been reported very rarely in patients receiving erlotinib as a complication of mucocutaneous inflammation. 3 Can lead to dehydration, hypokalaemia and renal failure. 4 Some cases have been associated with concomitant warfarin administration (see section 4.5) and some with concomitant NSAID administration. 5 These were mainly mild or moderate in severity, transient in nature or associated with liver metastases. 6 Confounding factors have included pre-existing liver disease or concomitant hepatotoxic medications (see section 4.4) . 7 In general, rash manifests as a mild or moderate erythematous and papulopustular rash, which may occur or worsen in sun exposed areas. 8 Acne, dermatitis acneiform and folliculitis, as mild to moderate and non-serious.

Adverse reactions such as diarrhoea, rash as well as an increase in liver transaminase may occur, in events where patients are exceeding the recommended 150 mg dose. In cases of suspected overdose, ERLOCIP treatment should be withheld, and symptomatic treatment should be initiated.