Erlotinib-native (Erlotinib-nativ)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceErlotinibErlotinib
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    • Dosage form: & nbspfilm-coated tablets
    Composition:

    Composition per 1 tablet:

    Component

    Amount, mg

    25 mg

    100 mg

    150 mg

    Active substance:

    Erlotinib hydrochloride (in terms of erlotinib)

    27,32

    (25,00)

    109,29

    (100,00)

    163,93

    (150,00)

    Excipients:

    Microcrystalline cellulose

    35,0

    88,5

    132,75

    Sodium lauryl sulfate

    1,0

    3,0

    4,5

    Sodium carboxymethyl starch

    8,0

    24,0

    36,0

    Lactose Monohydrate

    27,43

    69,21

    103,82

    Magnesium stearate

    1,25

    6,0

    9,0

    Film Sheath:

    Film coating:

    Opaprai * II pink 03B240022 (hypromellose - 62.500%, titanium dioxide - 30.940%, macrogol - 6.250%, iron dye red oxide - 0.200%, iron dye oxide yellow - 0.090%, dye iron (II, III) oxide / iron oxide black 0.020%)

    4,0

    12,0

    -

    Film coating:

    Opadry® II white 85F48105 (alcohol, polyvinyl-46.9%, macrogol-23.6%, talc 17.4 %, titanium dioxide-12.1%)

    -

    -

    18,0
    Description:

    Dosage of 25 mg: round biconvex tablets, covered with a film shell of pink color. On the cross section, the nucleus is white or almost white in color.

    Dosage of 100 mg: round biconvex tablets, covered with a film shell of pink color. On the cross section, the nucleus is white or almost white in color.

    Dosage of 150 mg: round biconvex tablets, covered with a film coating of white color. On the cross section, the nucleus is white or almost white in color.

    Pharmacotherapeutic group:Antitumor agent protein tyrosine kinase inhibitor
    ATX: & nbsp

    L.01.X.E.03   Erlotinib

    Pharmacodynamics:

    Erlotinib potently inhibits intracellular phosphorylation of the epidermal growth factor receptor HER1/EGFR (HER1 = epidermal growth factor receptor lth type / EGFR = epidermal growth factor receptor).

    Expression HER1/EGFR is observed on the surface of both normal and cancer cells. In preclinical models, inhibition of phosphotyrosine EGFR inhibits the growth of tumor cell lines and / or leads to their death.

    Mutations EGFR can lead to a constant activation of proliferative and anti-apoptotic signaling pathways in the cell. The high effectiveness of erlotinib in terms of blocking EGFR-dependent signaling pathways in tumors bearing a mutation EGFR, is due to the strong binding of erlotinib to the ATP-binding site of the mutated kinase domain EGFR. At the same time, the cascade of signaling reactions is blocked, as a result of which cell proliferation is inhibited and the internal pathway of cell death starts.

    Pharmacokinetics:

    Exposition

    After oral administration of 150 mg erlotinib in equilibrium, the median maximum concentration of erlotinib (CmOh) in plasma 1.995 ng / ml. Before taking the next dose after 24 hours, the median of the minimum concentration (Cmin) erlotinib in plasma at 1.238 ng / ml. The median area under the curve "concentration of active substance - time" (AUC) in the inter-dose interval, when the equilibrium concentration is reached, is 41.3 μg / h * ml.

    Suction

    Erlotinib is well absorbed after ingestion. Has a long-term suction phase, and the mean time to reach the maximum concentration (TCmOh) in blood plasma is 4 hours. According to the study with the participation of healthy volunteers, the bioavailability of erlotinib is 59%, eating can increase its bioavailability.

    After absorption in the blood erlotinib 95% is in a bound state, primarily with blood plasma proteins (albumin and alpha 1-acid glycoprotein). The free fraction is approximately 5%.

    Distribution

    Apparent volume of distribution of 232 l with distribution into the tumor tissue. In the samples of human tumor tissue on the 9th day of treatment with erlotinib at a dose of 150 mg per day, the average concentration of erlotinib is 1.185 ng / g, which is 63% of CmOh in blood plasma in an equilibrium state. The concentration of the main active metabolites in the tumor tissue is 160 ng / g, which corresponds to 113% CmOh in blood plasma in an equilibrium state. Studies on the study of distribution in tissues of the labeled 14With erlotinib after oral administration in athymic mice with a gene mutation nude with HT5 tumor xenograft (using a common autoradiography) showed a rapid and intensive distribution in tissues. FROMmOh in the tissue was about 73% of the concentration of erlotinib, TSmOh in the fabric - 1 hour.

    Metabolism

    Erlotinib is metabolized by isoenzymes of the cytochrome P450 system mainly with the participation of the isoenzyme CYP3A4 and to a lesser extent isoenzyme CYP1A2. Extrahepatic metabolism by isoenzyme CYP3A4 in the intestine, isoenzyme CYP1A1 in the lungs, isoenzyme CYP1B1 in the tumor tissue provides the metabolic clearance of erlotinib. Research in vitro indicate that 80-95% of erlotinib is metabolized with the participation of the isoenzyme CYP3A4.

    Metabolism occurs in three ways:

    1) O-demethylation of one of the side or both chains followed by oxidation to carboxylic acids;

    2) oxidation of the acetylene moiety of the molecule followed by hydrolysis to arylcarboxylic acid;

    3) aromatic hydroxylation of the phenylacetylene moiety.

    The main metabolites are formed as a result of O-demethylation of one of the lateral chains and have activity comparable to erlotinib in preclinical studies in vitro and on models of tumors in vivo. They are present in blood plasma at concentrations that are <10% erlotinib concentrations. The pharmacokinetics of metabolites is similar to the pharmacokinetics of erlotinib.

    Excretion

    Metabolites and trace amounts of erlotinib are excreted mainly with bile (> 90%), a small amount of orally administered dose is excreted by the kidneys.

    Clearance

    With monotherapy with erlotinib, the average clearance is 4.47 l / h, and the average half-life (T 1/2) is 36.2 hours. Consequently, it is expected that the equilibrium the concentration will be reached on the 7th - 8th day. There was no significant relationship between the clearance, age, body weight, sex and race of the patient.

    The pharmacokinetics of erlotinib depends on the following indicators: the concentrations of total bilirubin, alpha-1-acid glycoprotein and smoking at the present time. The decrease in clearance of erlotinib is noted with an increase in the concentration of total bilirubin and alpha 1-acid glycoprotein, and its increase in smokers.The simultaneous use of gemcitabine does not affect the clearance of erlotinib.

    Pharmacokinetics the separate patient groups

    Special studies of pharmacokinetics in children and elderly and older patients have not been conducted.

    Patients with hepatic impairment

    Erlotinib is mainly excreted with bile. Exposure erlotinib is the same in patients with an average degree of impaired liver function (7-9 points on the Child-Pugh scale) and in patients without disturbance of the function of baking, including in patients with a primary tumor focus in the liver or with metastases to the liver.

    Patients with impaired renal function

    Erlotinib and its metabolites are excreted by the kidneys in small amounts - less than 9% of a single dose. Clinical studies in patients with impaired renal function were not performed.

    Smoking

    Smoking increases clearance and reduces the exposure of erlotinib. AUC0-infinity Smoking people makes up 1/3 of AUC0-infinity For non-smokers / ex-smokers. The observed decrease in exposure in active smokers is probably due to induction of the isoenzyme CYP1A1 in the lungs and isoenzyme CYP1A2 in the liver.

    In smokers with non-small cell lung cancer (NLMW), the minimum equilibrium concentration is 0.65 μg / ml, which is 2 times lower,than for non-smokers / ex-smokers (1.28 μg / ml). At the same time, the apparent clearance of erlotinib increases by 24%.

    With an increase in the dose of erlotinib from 150 mg to 300 mg (the maximum tolerated dose), a dose-dependent increase in erlotinib exposure is observed. The minimum equilibrium concentration of erlotinib at a dose of 300 mg in smokers is 1.22 μg / ml.

    Indications:

    1) Non-small cell lung cancer.

    - The first line of topical or metastatic therapy (IIIB-IV stage) of non-small cell lung cancer with activating mutations in the gene EGFR.

    - Supportive therapy of locally advanced or metastatic non-small cell lung cancer in the absence of disease progression after 4 courses of the first line of chemotherapy on the basis of platinum preparations.

    - Locally distributed or metastatic non-small cell lung cancer after failure of one or more chemotherapy regimens.

    2) Pancreas cancer.

    - The first line of therapy for locally advanced or metastatic pancreatic cancer in combination with gemcitabine.

    Contraindications:

    - Hypersensitivity to erlotinib or to any component of the drug.

    - Pregnancy and the period of breastfeeding.

    - Age to 18 years (safety and efficacy not studied).

    - Severe hepatic (10 or more on the Child-Pugh score) and kidney failure.

    Carefully:

    - The average degree of hepatic insufficiency.

    - Smoking.

    - Patients with rare hereditary diseases, such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption.

    - Simultaneous reception with powerful inducers or inhibitors of isoenzyme CYP3A4.

    - Peptic ulcer or diverticular disease is currently or in history.

    - Simultaneous reception with anti-angiogenic drugs, glucocorticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs).

    - Patients receiving chemotherapy, which includes taxanes.

    - Simultaneous reception with P-glycoprotein inhibitors.

    Pregnancy and lactation:

    The use of the drug Erlotinib-native during pregnancy and during breastfeeding is contraindicated.

    Dosing and Administration:

    Inside, once a day, not less than 1 hour or 2 hours after eating.

    Non-small cell lung cancer

    150 mg daily.If there is evidence of disease progression or development of intolerable toxicity, erlotinib therapy should be discontinued.

    Before starting treatment in patients with non-small cell lung cancer who had not previously received chemotherapy, it is necessary to perform an analysis for the presence of a mutation L858R in 21 exon or a deletion in the 19 exon of the gene EGFR.

    Pancreas cancer

    For 100 mg daily, long-term, in combination with gemcitabine (see instructions for medical use of gemcitabine, indication of pancreatic cancer).

    If there is evidence of progression of the disease, erlotinib therapy should be discontinued.

    If the patient does not develop a rash within 4-8 weeks of treatment, further therapy with erlotinib should be reviewed.

    Special instructions for dosing

    With concomitant therapy, substrates or isoenzyme modulators CYP3A4 may require a change in the dose of erlotinib.

    If necessary, the dose of erlotinib decreases by 50 mg gradually.

    Impaired liver function

    Despite the fact that the exposure of erlotinib is the same in patients with moderate hepatic impairment (7-9 points on the Child-Pugh scale) and in patients without impaired liver function, caution should be exercised in appointing erlotinib to patients with impaired hepatic function.The use of erlotinib is not recommended for severe hepatic insufficiency.

    In the development of severe adverse reactions, consideration should be given to reducing the dose or interrupting therapy with erlotinib. Safety and efficacy in patients with severe hepatic insufficiency (activity of alanine aminotransferase (ALT) and aspartate aminotransferase (ACT) more than 5 times higher than the upper limit of the norm) have not been studied.

    Impaired renal function

    Safety and effectiveness in patients with impaired renal function (serum creatinine concentration more than 1.5 times higher than the upper limit of normal) have not been studied. According to pharmacokinetic data, no correction of the dose is required for renal failure of mild to moderate severity. The use of erlotinib is not recommended for severe renal failure.

    Childhood

    The safety and effectiveness of erlotinib in patients under the age of 18 years have not been studied.

    Smoking

    Smoking reduces the exposure of erlotinib by 50 - 60%. The maximum tolerated dose of erlotinib in smoking patients with non-small cell lung cancer is 300 mg.Long-term results of the efficacy and safety of doses above the recommended at the beginning of treatment, patients who continue to smoke, have not been established.

    Side effects:

    The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems. The incidence of undesirable reactions is estimated as follows: "very often" arising -> 10%; "often" -> 1% and <10%, "infrequently" -> 0.1% and <1%, "rarely" -> 0.01% and <0.1%, "very rarely" - <0, 01%, including individual messages, "frequency unknown".

    Disorders from the metabolism and nutrition: very often - anorexia.

    Disorders from the psyche: Often - Depression.

    Disturbances from the nervous system: Often - headache, neuropathy.

    Disturbances on the part of the organ of sight: Often - conjunctivitis, dry keratoconjunctivitis; often - keratitis; infrequently - impaired eyelash growth, including ingrown eyelashes, excessive growth and thickening of the eyelashes; rarely - ulceration and perforation of the cornea, uveitis.

    Disturbances from the respiratory system, chest and mediastinal organs: Often - shortness of breath, cough; often - nasal bleeding; infrequently - symptoms similar to interstitial lung diseases, including fatal cases.

    Disorders from the gastrointestinal tract: very often - diarrhea, nausea, vomiting, stomatitis, abdominal pain, flatulence, indigestion; often - gastrointestinal bleeding (including isolated fatal cases), some of which were associated with simultaneous use of warfarin or NSAIDs (non-steroidal anti-inflammatory drugs); infrequently - perforation of the gastrointestinal tract, in some cases with a fatal outcome.

    Disorders from the liver and bile ducts: often - violations of the liver (including increased activity ACT and ALT, increased bilirubin concentration); rarely - hepatic insufficiency (including fatal outcome).

    Disturbances from the skin and subcutaneous tissues: very often - rash (erythematous and papulo-pustular eruptions that appear or are intensified by exposure to sunlight), itching, dry skin, alopecia; often - Paronychia, skin cracks, usually not serious,in most cases associated with rash and dry skin, acne, acneiform dermatitis, folliculitis (in most cases, these adverse events were not serious, mild and moderate severity); infrequently - hyperpigmentation, hirsutism, changes in eyelashes and eyebrows, fragility and bundle of nails; there are cases of development of bullous, exfoliative and accompanied by formation of blistering skin lesions, including very rare cases of suspected development of Stevens-Johnson syndrome / toxic epidermal necrolysis, in some cases fatal.

    Disorders from the kidneys and urinary tract: often - kidney failure, infrequently - nephritis, proteinuria.

    General disorders and disorders in places of administration: very often - increased fatigue, severe infections (with or without neutropenia, pneumonia, sepsis, phlegmon), fever, chills, weight loss.

    Overdose:

    A single intake of erlotinib inwards at a dose of up to 1000 mg by healthy volunteers and up to 1600 mg once a week was well tolerated by patients with cancer.However, repeated administration of erlotinib 200 mg twice a day by healthy volunteers was not tolerated in a few days.

    Symptoms

    When taking erlotinib in a dose higher than recommended, severe adverse reactions, such as diarrhea, skin rashes and possibly an increase in the activity of "liver" transaminases, can be observed.

    Treatment

    In case of suspicion of an overdose, the treatment is suspended and symptomatic therapy is performed.

    The antidote to erlotinib is unknown.

    Interaction:

    Erlotinib in humans is metabolized by isoenzymes of the cytochrome P450 system, mainly with the participation of the isoenzyme CYP3A4 and to a lesser extent CYP1A2 and pulmonary isoenzyme CYP1A1. It is possible to interact with erlotinib in combination with inhibitors or inducers of isoenzymes, as well as drugs that are metabolized by these isoenzymes.

    Powerful inhibitors of isoenzyme CYP3A4 reduce the metabolism of erlotinib and increase its concentration in the blood plasma.

    Inhibition of isoenzyme metabolism CYP3A4 Under the influence ketoconazole (200 mg orally 2 times a day for 5 days) leads to an increase AUC erlotinib by 86% and CmOh on 69% in comparison with the same parameters at reception of one erlotinib.

    Ciprofloxacin (inhibitor of isoenzyme CYP3A4 and CYP1A2) increases the AUC and FROMmOh erlotinib by 39% and 17% respectively. The simultaneous use of erlotinib with potent inhibitors of isoenzyme CYP3A4 or CYP3A4/CYP1A2 is carried out only when absolutely necessary. In case of development of toxicity, a dose of erlotinib should be reduced.

    Powerful inducers of isoenzyme CYP3A4 increase the metabolism of erlotinib and significantly reduce its concentration in the blood plasma. Induction of metabolism involving isoenzyme CYP3A4 with simultaneous application of rifampicin (600 mg orally daily for 7 days) leads to a decrease in the median AUC erlotinib in a dose of 150 mg to 69% compared with the use of a single erlotinib.

    After preliminary treatment with rifampicin, as well as with the simultaneous use of rifampicin and erlotinib, the median AUC erlotinib in a dose of 450 mg is 57.5% of AUC erlotinib in a dose of 150 mg without prior therapy with rifampicin. If possible, an alternative treatment should be provided without induction of isoenzyme activity CYP3A4. Simultaneous application erlotinib with powerful isoenzyme inducers CYP3A4, such as rifampicin, is made only when absolutely necessary, and it is necessary to increase the dose of erlotinib up to 300 mg under a careful control of the safety profile. With good tolerability, when erlotinib is used for more than 2 weeks, an increase in the dose of erlotinib to 450 mg can be considered while continuing to closely monitor the safety profile (see section "Special instructions"). Higher doses in such situations have not been studied.

    Reduction of erlotinib concentration is possible and with simultaneous application with other inducers CYP3A4, for example, phenytoin, carbamazepine, barbiturates or preparations of St. John's wort perfumed. Care should be taken when using inducers CYP3A4 and erlotinib. If possible, an alternative treatment should be provided without the powerful induction of isoenzyme activity CYP3A4.

    Substrates of the isoenzyme CYP3A4

    Prior therapy or simultaneous administration of erlotinib does not disrupt the clearance of typical isoenzyme substrates CYP3A4, such as midazolam and erythromycin. Thus, the significant effect of erlotinib on the clearance of other isoenzyme substrates CYP3A4 unlikely. It turned out that the bioavailability of midazolam with oral intake is reduced by 24%, which is not related to the effect on isoenzyme activity CYP3A4.

    Erlotinib and proteasome inhibitors

    According to the mechanism of action of proteasome inhibitors (eg, bortezomib), one can expect an effect on the effect of inhibitors EGFR, including erlotinib. This interaction is confirmed by a limited number of clinical and preclinical studies showing degradation EGFR by means of proteasomes.

    Erlotinib and P-glycoprotein inhibitors

    Erlotinib is the substrate of the active substance of the carrier of P-glycoprotein (P-gp). The simultaneous use of erlotinib and inhibitors P-gp (eg, cyclosporine and verapamil), may result in a change in the distribution and / or elimination of erlotinib. The question of this drug interaction and toxic effects on the central nervous system has not been adequately studied, and therefore caution should be exercised while using erlotinib and inhibitors P-gp.

    Drugs that change the pH in the digestive tract

    The solubility of erlotinib depends on the pH of the medium.When the pH of the medium rises above 5, the solubility of erlotinib decreases. Thus, drugs that alter pH in the upper gastrointestinal tract can affect the solubility of erlotinib and its bioavailability. With the simultaneous use of erlotinib and omeprazole, a proton pump inhibitor, AUC and CmOh erlotinib are reduced by 46% and 61% respectively. TSmOh and T1 / 2 do not change. With the simultaneous use of erlotinib and ranitidine (300 mg), the blocker of Ng-histamine receptors, AUC and CmOh erlotinib are reduced by 33% and 54% respectively.

    Thus, whenever possible, avoid the simultaneous use of erlotinib and drugs that reduce the secretion of the glands of the stomach. It is unlikely that an increase in the dose of erlotinib with simultaneous application with such drugs can compensate for a decrease in its exposure. However, in cases where erlotinib appoint in different hours, i.e. 2 hours before or 10 hours after taking ranitidine (150 mg twice a day), AUC and CmOh erlotinib are reduced only by 15% and 17% respectively. If necessary, therapy with these drugs should be preferred to the use of H2-histamine receptor blockers,such as ranitidine, at different hours. Should be taken erlotinib at least 2 hours before or 10 hours after administration of the H2-histamine receptor blocker.

    Warfarin, other coumarin derivatives

    There is evidence of an increase in the international normalized relationship (INR) and the development of bleeding, in some cases fatal, in patients receiving erlotinib in combination with coumarin derivatives, including warfarin. Patients taking coumarin derivatives should regularly monitor prothrombin time or INR.

    Statins

    Erlotinib in combination with statins can enhance myopathy caused by statins, including rhabdomyolysis (rarely seen).

    Smoking

    Smoking cessation should be recommended when using erlotinib, since smoking, inducing isoenzymes CYP1A1 and CYP1A2, reduces the exposure of erlotinib by 50 - 60%.

    Gemcitabine

    There was no significant effect of gemcitabine on the pharmacokinetics of erlotinib and vice versa.

    Preparations of platinum

    Erlotinib increases the concentration of platinum in the blood plasma. Simultaneous reception of erlotinib with carboplatin and paclitaxel leads to a statistically significant but not significant clinical increase AUC of total platinum by 10.6%.An increase in the exposure of carboplatin may be associated with other factors, for example, impaired renal function. There was no significant effect of carboplatin or paclitaxel on the pharmacokinetics of erlotinib.

    Capecitabine

    Capecitabine increases the concentration of erlotinib in the blood plasma. The use of erlotinib in combination with capecitabine compared with erlotinib monotherapy results in a statistically significant increase AUC erlotinib and a slight increase in CmOh erlotinib. There was no significant effect of erlotinib on the pharmacokinetics of capecitabine.

    Substrates UGT1A1

    Because the erlotinib is an inhibitor of UDP-glucuronyl transferase UGT1A1, it is possible to interact with drugs that are substrates UGT1A1 and for which the conjugation reaction with glucuronic acid is the main pathway of metabolism. Caution should be exercised when prescribing erlotinib for patients with low levels of expression UGT1A1 or with genetic disorders that cause a decrease in the rate of the glucuronization reaction (for example, Gilbert's syndrome), since an increase in the concentration of bilirubin in the blood plasma is possible.

    Special instructions:

    Assessment of the status of mutations in the gene EGFR. When assessing the status of mutations in a gene EGFR patients with locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy should choose well-tested and reliable assays to avoid false negative or false positive definitions.

    Smoking. Smoking patients should be advised not to smoke, as the concentration of erlotinib in the blood plasma in smokers compared with non-smokers is significantly reduced.

    Interstitial lung disease (PID). In patients with non-small cell lung cancer, pancreatic cancer or other common solid tumors receiving erlotinib, IZL-like symptoms, including those with a fatal outcome, are rarely diagnosed. The overall incidence of ILE-like events in patients receiving erlotinib, is 0.6%. The most frequent diagnoses in patients with suspected ILE-like symptoms are: pneumonitis, interstitial pneumonia, radiation pneumonitis, allergic interstitial pneumonitis, interstitial lung disease,bronchiolitis obliterans, pulmonary fibrosis, acute respiratory distress syndrome, pulmonary infiltration and alveolitis. These ILD-like events occur during the period of from several days to several months after initiation of therapy with erlotinib and are most commonly associated with aggravating or contributing factors such as concomitant or prior of chemotherapy, radiation therapy, parenchymal lung disease history, metastatic lung disease or infection .

    In acute development of new and / or progressive unexplained pulmonary symptoms (dyspnea, cough, and fever), erlotinib is necessary to temporarily stop to determine the cause. In case of confirmation of the diagnosis of IZL it is necessary to cancel erlotinib and carry out the necessary treatment.

    Diarrhea, dehydration, electrolyte disorders and renal failure. If severe or moderate diarrhea occurs, loperamide. In some cases, a reduction in the dose of erlotinib may be required.

    In severe or resistant diarrhea, nausea, anorexia, vomiting or dehydration, erlotinib therapy should be interrupted and held rehydration.There are reports of rare cases of hypokalemia and renal insufficiency, including fatal outcome.

    Some cases of kidney failure were caused by severe dehydration due to diarrhea, vomiting and / or anorexia, others - concomitant chemotherapy. In cases of severe or persistent diarrhea, or conditions leading to dehydration, especially in patients at risk (concomitant therapy or disease, or in the presence of other predisposing factors, including the elderly), erlotinib are temporarily withdrawn and parenteral rehydration is carried out. Patients with a high risk of dehydration should monitor serum electrolytes, including potassium, and kidney function.

    Hepatitis, hepatic insufficiency. In rare cases, erlotinib may develop liver failure (there is information about cases with lethal outcome). It is recommended to periodically monitor liver function in patients with concomitant liver disease or receiving hepatotoxic drugs. With the development of severe liver damage, erlotinib is discontinued.

    Perforation of the gastrointestinal tract. There is evidence of an increased risk of developing gastrointestinal perforation in patients taking erlotinib, which is observed infrequently, in some cases with a fatal outcome. The high-risk group includes patients receiving concomitant therapy with anti-angiogenic drugs, glucocorticosteroids, NSAIDs and / or taxane-based chemotherapy, or patients having a history of peptic ulcer or diverticular disease.

    In the case of development of perforation of the gastrointestinal tract, erlotinib therapy should be discontinued.

    Bullous or exfoliative disorders. There are cases of bullous, accompanied by the formation of blisters and exfoliative disorders, including very rare cases of suspected development of the Stevens-Johnson syndrome / toxic epidermal necrolysis, in some cases fatal. In the case of the development of severe bullous, accompanied by the formation of blisters or exfoliative skin lesions, treatment with erlotinib should be suspended or discontinued.

    Ophthalmic disorders. When using erlotinib, very rare cases of perforation or ulceration of the cornea have been recorded. Other ophthalmic disorders, including abnormal eyelash growth, dry keratoconjunctivitis or keratitis, which are also risk factors for perforation / ulceration of the cornea, are also observed with erlotinib treatment. Treatment with erlotinib should be suspended or canceled if acute ophthalmic symptoms such as eye pain or worsening of chronic ophthalmic diseases occur.

    Contraception. During treatment with erlotinib and at least 2 weeks after the end, reliable contraceptive methods should be used.

    Disposal of the drug. Dispose of the drug in accordance with local requirements.

    Effect on the ability to drive transp. cf. and fur:

    Studies on the effect of erlotinib on the ability to drive vehicles and mechanisms have not been carried out. but erlotinib does not affect on the ability to concentrate. In case of development of undesirable reactions from the organs of vision,nervous system or psyche in the use of the drug should refrain from the management of vehicles and mechanisms, as well as from the employment of other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

    Form release / dosage:

    Tablets, film-coated 25 mg, 100 mg and 150 mg.

    Packaging:

    30 tablets in cans of polyethylene terephthalate, sealed with polyethylene caps. On cans stick a label.

    10 tablets per contour cell packaging made of polyvinylchloride film and foil of aluminum laminated printed, or polyvinylchloride / polyvinylidene chloride film and aluminum foil laminated printed.

    For 1 bank, 3 contour squares, together with instructions for use, are placed in a cardboard box.

    Storage conditions:

    In the dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    4 years.

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-004608
    Date of registration:21.12.2017
    Expiration Date:21.12.2022
    The owner of the registration certificate:NATIVA, LLC NATIVA, LLC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp24.01.2018
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