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  • Erbitux
    / Merck


    Active Ingredient
    Cetuximab 5 mg/ml

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    100 ml

    partial basket chart 85543 5531

    Vial

    20 ml

    partial basket chart 85542 5530

    Related information


    Dosage

    Prior to the first infusion, patients must receive premedication with an antihistamine and a corticosteroid at least 1 hour prior to administration of Cetuximab. This premedication is recommended prior to all subsequent infusions. In all indications, Erbitux is administered once a week. The initial dose is 400 mg Cetuximab per m2 body surface area. All subsequent weekly doses are 250mg Cetuximab per m2 each.
    Colorectal cancer: In patients with metastatic colorectal cancer, Cetuximab is used in combination with chemotherapy or as a single agent. Evidence of wild-type RAS (RAS and NRAS) status is required before initiating treatment with Cetuximab. Mutational status should be determined by an experienced laboratory using validated test methods for detection of RAS and NRAS (exons 2, 3, and 4) mutations.
    For the dosage or recommended dose modifications of concomitantly used chemotherapeutic agents, refer to the product information for these medicinal products. They must not be administered earlier than 1 hour after the end of the Cetuximab infusion. It is recommended that Cetuximab treatment be continued until progression of the underlying disease.
    Squamous cell cancer of the head and neck: In patients with locally advanced squamous cell cancer of the head and neck, Cetuximabis used concomitantly with radiation therapy. It is recommended to start Cetuximab therapy one week before radiation therapy and to continue Cetuximab therapy until the end of the radiation therapy period.
    In patients with recurrent and/or metastatic squamous cell cancer of the head and neck, Cetuximab is used in combination with platinumbased chemotherapy followed by Cetuximab as maintenance therapy until disease progression. Chemotherapy must not be administered earlier than 1 hour after the end of the Cetuximab infusion.
    In patients with recurrent and/or metastatic squamous cell cancer of the head and neck, Cetuximab is used as monotherapy. It is recommended that treatment be continued until progression of the underlying disease.
    Method of Administration: The drug administered intravenously with an infusion pump, gravity drip or a syringe pump. The initial dose should be given slowly and speed of infusion must not exceed 5 mg/min. The recommended infusion period is 120 minutes. For the subsequent weekly doses, therecommended infusion period is 60 minutes. The infusion rate must not exceed 10 mg/min.


    Indications

    Treatment of patients with epidermal growth factor receptor (EGFR)-expressing, RAS Wild-type metastatic colorectal cancerin combination with irinotecan-based chemotherapy. In 1st -line in combination with FOLFOX, as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan.
    Treatment of patients with squamous cell cancer of the head and neck (SCCHN).
    In combination with radiation therapy for locally advanced disease in combination with platinum-based chemotherapy for recurrent and/or metastatic disease. As a single agent after failure of platinum-based chemotherapy for recurrent and/or metastatic disease. Must be administered under the supervision of a physician experienced in the use of antineoplastic medicinal products. Close monitoring is required during the infusion and for at least 1 hour after the end of the infusion. Availability of resuscitation equipment must be ensured.


    Contra-Indications

    Severe (grade 3 or 4)  hypersensitivity  reactions to Cetuximab. Combination with Oxaliplatin-containing chemotherapy is contraindicated for patients with mutant RASmetastatic colorectal cancer (mCRC) or for whom RASmCRC status is unknown.
    Before initiation of combination treatment, contraindications for concomitantly used chemotherapeutic agents or radiation therapy must be considered.


    Special Precautions

    Infusion-related, including anaphylactic, reactions: Severe infusion-related reactions, including anaphylactic reactions, may commonly occur, in some cases with fatal outcome. Occurrence of a severe infusion-related reaction requires immediate and permanent discontinuation of Cetuximab therapy and may necessitate emergency treatment. Some of these reactions may be anaphylactic or anaphylactoid in nature or represent a cytokine release syndrome (CRS). Symptoms may occur during the first infusion and for up to several hours afterwards or with subsequent infusions. It is recommended to warn patients of the possibility of such a late onset and instruct them to contact their physician if symptoms or signs of an infusion-related reaction occur.
    Symptoms may include bronchospasm, urticaria, increase or decrease in blood pressure, loss of consciousness or shock. In rare cases, angina pectoris, myocardial infarction or cardiac arrest have been observed.
    Respiratory disorders: Cases of interstitial lung disease have been reported, with the majority of patients from the Japanese population. If interstitial lung disease is diagnosed,  Cetuximab must be discontinued and the patient be treated appropriately.
    Skin reactions: Main adverse reactions of Cetuximab are skin reactions which may become severe, especially in combination with chemotherapy. The risk for secondary infections (mainly bacterial) is increased and cases of staphylococcal scalded skin syndrome, necrotising fasciitis and sepsis, in some cases with fatal outcome, have been reported. Skin reactions are very common and treatment interruption or discontinuation may be required. According to clinical practice guidelines prophylactic use of oral tetracyclines (6 – 8 weeks) and topical application of 1% hydrocortisone cream with moisturiser should be considered. Medium to high-potency topical corticosteroids or oral tetracyclines have been used for the treatment of skin reactions. If a patient experiences an intolerable or severe skin reaction (≥ grade 3; – Common Terminology Criteria for Adverse Events, CTCAE), Cetuximab therapy must be interrupted. Treatment may only be resumed, if the reaction has resolved to grade 2. If the severe skin reaction occurred for the fi rst time, treatment may be resumed without any change in dose level. With the second and third occurrences of severe skin reactions, Cetuximab therapy must again be interrupted. Treatment may only be resumed at a lower dose level (200 mg/m² body surface area after the second occurrence and 150 mg/m² after the third occurrence), if the reaction has resolved to grade 2. If severe skin reactions   occur a fourth time or do not resolve to grade 2 during interruption of treatment, permanent discontinuation of Cetuximab treatment is required.
    Electrolyte disturbances: Progressively decreasing serum magnesium levels occur frequently and may lead to severe hypomagnesaemia. Hypomagnesaemia is reversible following discontinuation of Cetuximab. In addition, hypokalaemia may develop as a consequence of diarrhea. Hypocalcaemia may also occur; in particular in combination with platinum-based chemotherapy the frequency of severe hypocalcaemia may be increased. Determination of serum electrolyte levels is recommended prior to and periodically during Cetuximab treatment. Electrolyte repletion is recommended, as appropriate. Neutropenia and related infectious complications.
    Patients who receive Cetuximab in combination with platinum-based chemotherapy are at an increased risk for the occurrence of severe neutropenia, which may lead to subsequent infectious complications such as febrile neutropenia, pneumonia or sepsis. Careful monitoring is recommended in such patients, in particular in those who experience skin lesions, mucositis or diarrhoea that may facilitate the occurrence of infections.
    Cardiovascular disorders: An increased frequency of severe and sometimes fatal cardiovascular events and treatment emergent deaths has been observed in the treatment of non-small cell lung cancer, squamous cell carcinoma of the head and neck and colorectal carcinoma. In some studies association with age ≥ 65 years or performance status has been observed. When prescribing cetuximab, the cardiovascular status and performance status of the patients and concomitant administration of cardiotoxic compounds such as fl uoropyrimidines should be taken into account.
    Eye disorders:Patients presenting with signs and symptoms suggestive of keratitis such as acute or worsening: eye infl ammation, 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 Cetuximab should be interrupted or discontinued. If keratitis is diagnosed, the benefi ts and risks of continuing treatment should be carefully considered. Cetuximab 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. Colorectal cancer patients with RAS mutated tumours Cetuximab should not be used in the treatment of colorectal cancer patients whose tumours have RAS mutations or for whom RAS tumour status is unknown. Results from clinical studies show a negative benefi t-risk balance in tumours with RAS mutations. In particular, in these patients negative eff ects on progression-free survival (PFS) and overall survival (OS) were seen as add-on to FOLFOX4 .
    Similar fi ndings were also reported when Cetuximab was given as add-on to XELOX in combination with bevacizumab (CAIRO2). However, in this study no positive eff ects on PFS or OS were demonstrated in patients with RASwild-type tumours, either.
    Special Populations: Only patients with adequate renal and hepatic function have been investigated to date (serum creatinine ≤ 1.5 fold, transaminases ≤ 5 fold and bilirubin ≤ 1.5 fold the upper limit of normal). Cetuximab has not been studied in patients presenting with one or more of the following laboratory parameters: Hemoglobin < 9 g/dl, Leukocyte count < 3000/mm³.
    See prescribing information for full details.


    Side Effects

    Headache, conjunctivitis, diarrhea, nausea, vomiting. Skin reactions. Hypomagnesemia, dehydration (in particular secondary to diarrhea or mucositis), hypocalcemia, anorexia which may lead to weight decrease. Mild or moderate infusion-related reactions, mild to moderate mucositis which may lead to epistaxis. Severe infusion-related reactions, fatigue.
    See prescribing information for full details.


    Drug interactions

    In combination with platinum-based chemotherapy, the frequency of severe leukopenia or severe neutropenia may be increased, and thus may lead to a higher rate of infectious complications such as febrile neutropenia, pneumonia and sepsis compared to platinum-based chemotherapy alone.
    In combination with fl uoropyrimidines, the frequency of cardiac ischaemia including myocardial infarction and congestive heart failure as well as the frequency of hand-foot syndrome (palmar-plantar erythrodysaesthesia) were increased compared to that with fl uoropyrimidines.
    In combination with Capecitabine and Oxaliplatin (XELOX) the frequency of severe diarrhoea may be increased. A formal interaction study showed that the pharmacokinetic characteristics of Cetuximab remain unaltered after co-administration of a single dose of irinotecan (350 mg/m2 body surface area). Similarly, the pharmacokinetics of irinotecan were unchanged when Cetuximab was co-administered.
    No other formal interaction studies with Cetuximab have been performed in humans.
    See prescribing information for full details.


    Pregnancy and Lactation

    EGFR (The epidermal growth factor receptor) is involved in fetal development. Sufficient data from pregnant or lactating women are not available.
    See prescribing information for full details. 


    Overdose

    There is limited experience with single doses higher than 400 mg/m2 body surface area to date or weekly administrations of doses higher than 250 mg/m2 body surface area.
    See prescribing information for full details.  


    Important notes

    Compatibilities: This medicinal product must not be mixed with other medicinal products except those: May be administered via a gravity drip, an infusion pump or a syringe pump. A separate infusion line must be used for the infusion, and the line must be fl used with sterile sodium chloride 9 mg/mL (0.9%) solution for injection at the end of infusion.
    Compatible with: Polyethylene (PE), ethyl vinyl acetate (EVA) or polyvinyl chloride (PVC) bags, Polyethylene (PE), polyurethane (PUR), ethyl vinyl acetate (EVA), polyolefi ne thermoplastic (TP) or polyvinyl chloride (PVC) infusion sets, Polypropylene (PP) syringes for syringe pump. Care must be taken to ensure aseptic handling when preparing the infusion.
    Storage: Store in a refrigerator (2°C – 8°C). Chemical and physical in-use stability of this drug has been demonstrated for 48 hours at 25°C, if the solution is prepared as described in prescribing information.
    This drug does not contain any antimicrobial preservative or bacteriostatic agent. From a microbiological point of view, the product shall be used immediately after opening. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless opening has taken place in controlled and validated aseptic conditions.


    Manufacturer
    Merck KgaA, Germany
    Licence holder
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