Erbitux 5mg/ml solution for infusion

  • Name:

    Erbitux 5mg/ml solution for infusion

  • Company:
    info
  • Active Ingredients:

    cetuximab

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 17/09/19

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Summary of Product Characteristics last updated on medicines.ie: 6/6/2019

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Merck

Merck

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When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 17 September 2019 PIL

Reasons for updating

  • Change to section 6 - manufacturer

Updated on 7 June 2019 PIL

Reasons for updating

  • Change to section 6 - marketing authorisation holder
  • Change to section 6 - date of revision

Updated on 6 June 2019 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 26 November 2018 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 9 June 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 9 June 2017 PIL

Reasons for updating

  • Change to section 4 - how to report a side effect

Updated on 16 December 2016 SmPC

Reasons for updating

  • Change to Section 4.8 – Undesirable effects - how to report a side effect

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.8 Undesirable effects - how to report a side effect - was updated with the addition of Malta. Internal Ref: TW1230178.

Updated on 16 December 2016 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 16 February 2015 PIL

Reasons for updating

  • Change to date of revision
  • Addition of information on reporting a side effect.
  • Change to how the medicine works

Updated on 4 August 2014 SmPC

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Changes are in Section 5.1 - Pharmacodynamic properties

Section 10 - now has a date of June 2014.

Updated on 25 April 2014 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 6.3 - Shelf life
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

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Additional information on the reporting of adverse reactions in section 4.8.
Shelf life increased to 4 years in section 6.3.

Updated on 18 March 2014 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to warnings or special precautions for use

Updated on 7 January 2014 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Update of the SPC regarding cytokine-releasing syndrome.

Update of the SPC to exclude patients who test positive for RAS mutation.

Updated on 5 June 2013 PIL

Reasons for updating

  • Change to side-effects
  • Deletion of a pack size

Updated on 22 March 2013 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.4 Special warnings and prcautions for use:
Skin Reaction

Main adverse reactions of cetuximab are skin reactions which may become severe, especially incombination with chemotherapy. The risk for secondary infections (mainly bacterial) is increased andcases of staphylococcal scalded skin syndrome, necrotising fasciitis and sepsis, in some cases withfatal outcome, have been reported (see section 4.8).

If a patient experiences an intolerable or a severe skin reaction (
grade 3; US National CancerInstitute - Common Terminology Criteria for Adverse Events, CTCAE), cetuximab therapy must beinterrupted. Treatment may only be resumed if the reaction has resolved to grade 2.

Section 4.8 Undesirable effects
Skin Reaction

Skin reactions may develop in more than 80% of patients and mainly present as acne-like rash and/or,less frequently, as pruritus, dry skin, desquamation, hypertrichosis, or nail disorders (e.g. paronychia).Approximately 15% of the skin reactions are severe, including single cases of skin necrosis. Themajority of skin reactions develop within the first three weeks of therapy. They generally resolve,without sequelae, over time following cessation of treatment if the recommended adjustments in doseregimen are followed (see section 4.4).Skin lesions induced by cetuximab may predispose patients to superinfections (e.g. with
S. aureus),which may lead to subsequent complications, e.g. cellulitis, erysipelas, or, potentially with fataloutcome, staphylococcal scalded skin syndrome, necrotising fasciitis or sepsis.

Updated on 25 February 2013 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.3 - Shelf life
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Throughout SPC:

was ml now mL

4.8 Undesirable effects

General disorders and administration site conditions

Very common: Mild or moderate infusion-related reactions*; mucositis, in some cases severe. Mucositis may lead to epistaxis.

Common: Severe infusion-related reactions*, fatigue.

10. DATE OF REVISION OF THE TEXT

01/2013

Updated on 10 September 2012 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 6.5 - Nature and contents of container
  • Change to section 8 - MA number

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Non-marketed vial sizes of 10ml and 50ml have been deleted. 
The stopper has changed in composition from flurotec-coated bromobutyl rubber to halobutyl rubber.

Updated on 8 June 2012 PIL

Reasons for updating

  • Change to storage instructions
  • Change to side-effects
  • Change to drug interactions
  • Change to date of revision

Updated on 10 April 2012 PIL

Reasons for updating

  • New PIL for medicines.ie

Updated on 10 February 2012 SmPC

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 

There are minor editorial changes in sections 2 and 3 of the SPC.

The main change is the update of the 5-year overall survival data in study EMR 62 202-006 in section 5.1. This is shown as follows by the red text:

     

Variable/ statistic

Radiation therapy + cetuximab

Radiation therapy alone

 

(N=211)

(N=213)

Locoregional control

 

 

 

 

months, median (95% CI)

24.4

(15.7, 45.1)

14.9

(11.8, 19.9)

Hazard Ratio (95% CI)

0.68 (0.52, 0.89)

p-value

0.005

OS

 

 

 

 

months, median (95% CI)

49.0

(32.8, 69.5+)

29.3

(20.6, 41.4)

Hazard Ratio (95% CI)

0.73 (0.56, 0.95)

p-value

0.018

median follow-up, months

1-year OS rate, % (95% CI)

2-year OS rate, % (95% CI)

3-year OS rate, % (95% CI)

5-year OS rate, % (95% CI)

                        60.0                                                           60.1

             77.6 (71.4, 82.7)                                          73.8 (67.3, 79.2)

             62.2 (55.2, 68.4)                                          55.2 (48.2, 61.7)

             54.7 (47.7, 61.2)                                          45.2 (38.3, 51.9)

             45.6 (38.5, 52.4)                                          36.4 (29.7, 43.1)    

        

 

Updated on 23 January 2012 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

(Changes highlighted in red)
4.1          Therapeutic indications

 

Erbitux is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type metastatic colorectal cancer

·                in combination with irinotecan-based chemotherapy,

·                in first-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.

For details, see section 5.1.

 

Erbitux is indicated for the treatment of patients with squamous cell cancer of the head and neck

·                in combination with radiation therapy for locally advanced disease,

·                in combination with platinum-based chemotherapy for recurrent and/or metastatic disease.

 

4.2          Posology and method of administration

Colorectal cancer

 

In patients with metastatic colorectal cancer, cetuximab is used in combination with chemotherapy or as a single agent (see section 5.1). Wild-type KRAS tumour status must be verified prior to the first cetuximab infusion. It is important that a validated test method is used by an experienced laboratory (see section 4.4 and 5.1).

Paediatric population

 

The efficacy of cetuximab in paediatric patients below the age of 18 years has not been established. No new safety signals were identified in paediatric patients as reported from a phase‑I study.

 

There is no relevant use of cetuximab in the paediatric population in the granted indications.

4.3          Contraindications

 

Erbitux is contraindicated in patients with known severe (grade 3 or 4) hypersensitivity reactions to cetuximab.

 

The combination of Erbitux with oxaliplatin-containing chemotherapy is contraindicated for patients with mutant KRAS metastatic colorectal cancer (mCRC) or for whom KRAS mCRC status is unknown (see also section 4.4).

 

Before initiation of combination treatment, contraindications for concomitantly used chemotherapeutic agents or radiation therapy must be considered.

4.4          Special warnings and precautions for use

Skin reactions 

(New paragraph added)
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........

Colorectal cancer patients with KRAS mutated tumours

 

Cetuximab should not be used in the treatment of colorectal cancer patients whose tumours have KRAS mutations or for whom KRAS tumour status is unknown. Results from clinical studies show a negative benefit-risk balance in tumours with KRAS mutations. In particular, in these patients negative effects on progression-free survival (PFS) and overall survival (OS) were seen as add-on to FOLFOX4 (see section 5.1).

 

Similar findings were also reported when cetuximab was given as add-on to XELOX in combination with bevacizumab (CAIRO2). However, in this study no positive effects on PFS or OS were demonstrated in patients with KRAS wild‑type tumours, either.

5.1          Pharmacodynamic properties

Paediatric population

 

The European Medicines Agency has waived the obligation to submit the results of studies with cetuximab in all subsets of the paediatric population in the indications adenocarcinoma of the colon and rectum and oropharyngeal, laryngeal or nasal epithelial carcinoma (excluding nasopharyngeal carcinoma or lymphoepithelioma, see section 4.2 for information on paediatric use).

10.          DATE OF REVISION OF THE TEXT

 

01/2012

Updated on 4 November 2011 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In Section 4.4 under the heading of Respiratory disorders the test now reads:
"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".

An additional paragraph is added under Eye 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 cetuximab should be interrupted or discontinued. If keratitis is diagnosed, the benefits 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".

Under Section 4.8 - Respiratory, thoracic and mediastinal disorders - now reads:

Respiratory, thoracic and mediastinal disorders

Uncommon:              Pulmonary embolism, interstitial lung disease.

Under heading Skin and subcutaneous tissue diosrders - now reads:
Very common:          Skin reactions*
Very rare:                 Stevens-Johnson syndrome/toxic epidermal necrolysis.
Frequency not known: Superinfection of skin lesions*.

 

 

Updated on 1 July 2011 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

changes are widespread throughout the document

Updated on 9 May 2011 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Following sections updated

4.2 Posology and method of administration

Paediatric population

The efficacy of cetuximab in paediatric patients below the age of 18 years has not been established. No new safety signals were identified in paediatric patients as reported from a phase-I study.

 

4.4 Special warnings and precautions for use

Paediatric population

The efficacy of cetuximab in paediatric patients below the age of 18 years has not been established. No new safety signals were identified in paediatric patients as reported from a phase-I study.

 

4.6

 

Fertility, pregnancy and lactation

 

Pregnancy

EGFR is involved in foetal development. Limited observations in animals are indicative of a placental transfer of cetuximab, and other IgG1 antibodies have been found to cross the placental barrier. Animal data revealed no evidence of teratogenicity. However, dependent on the dose, an increased incidence of abortion was observed (see section 5.3). Sufficient data from pregnant or lactating women are not available.

It is strongly recommended that Erbitux be given during pregnancy or to any woman not employing adequate contraception only if the potential benefit for the mother justifies a potential risk to the foetus.

Breastfeeding

It is recommended that women do not breast-feed during treatment with Erbitux and for 2 months after the last dose, because it is not known whether cetuximab is excreted in breast milk.

Fertility

There are no data on the effect of cetuximab on human fertility. Effects on male and female fertility have not been evaluated within formal animal studies (see section 5.3).

 

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studies with cetuximab in all subsets of the paediatric population in the granted indications (see section 4.2 for information on paediatric use).

 

5.2 Pharmacokinetic properties

Paediatric population

In a phase-I study in paediatric patients (1-18 years) with refractory solid tumours, cetuximab was administered in combination with irinotecan. The pharmacokinetic results were comparable to those in adults.

 

10. DATE OF REVISION OF THE TEXT

04/2011

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/.

Updated on 19 November 2010 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Inclusion of Aseptic Meningitis to section 4.8

4.8       Undesirable effects

 

The main undesirable effects of cetuximab are skin reactions, which occur in more than 80% of patients, hypomagnesaemia which occurs in more than 10% of patients and infusion-related reactions, which occur with mild to moderate symptoms in more than 10% of patients and with severe symptoms in more than 1% of patients.

 

The following definitions apply to the frequency terminology used hereafter:

 

Very common (³ 1/10)

Common (³ 1/100 to < 1/10)

Uncommon (³ 1/1,000 to < 1/100)

Rare (³ 1/10,000 to < 1/1,000)

Very rare (< 1/10,000)

Frequency not known (cannot be estimated from the available data)

 

An asterisk (*) indicates that additional information on the respective undesirable effect is provided below the table.

 

Metabolism and nutrition disorders

 

Very common:          Hypomagnesaemia (see section 4.4).

Common:                  Dehydration, in particular secondary to diarrhoea or mucositis; hypocalcaemia (see section 4.4); anorexia which may lead to weight decrease.

 

Nervous system disorders

 

Common:                  Headache.

Frequency not known: Aseptic meningitis.

 

Eye disorders

 

Common:                  Conjunctivitis.

Uncommon:              Blepharitis, keratitis.

 

Vascular disorders

 

Uncommon:              Deep vein thrombosis.

 

Respiratory, thoracic and mediastinal disorders

 

Uncommon:              Pulmonary embolism.

 

Gastrointestinal disorders

 

Common:                  Diarrhoea, nausea, vomiting.

 

Hepatobiliary disorders

 

Very common:          Increase in liver enzyme levels (ASAT, ALAT, AP).

 

Skin and subcutaneous tissue disorders

 

Very common:          Skin reactions*.

Frequency not known: Superinfection of skin lesions*.

 

General disorders and administration site conditions

 

Very common:          Mild or moderate infusion-related reactions*; mild to moderate mucositis which may lead to epistaxis.

Common:                  Severe infusion-related reactions*, fatigue.

 

 

Additional information

 

Overall, no clinically relevant difference between genders was observed.

 

Infusion-related reactions

 

Mild or moderate infusion-related reactions are very common comprising symptoms such as fever, chills, dizziness, or dyspnoea that occur in a close temporal relationship mainly to the first cetuximab infusion.

 

Severe infusion-related reactions may commonly occur, in rare cases with fatal outcome. They usually develop during or within 1 hour of the initial cetuximab infusion, but may occur after several hours or with subsequent infusions. Although the underlying mechanism has not been identified, some of these reactions may be anaphylactoid/anaphylactic in nature and may include symptoms such as 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.

 

For clinical management of infusion-related reactions, see section 4.4.

 

Skin reactions

 

Skin reactions may develop in more than 80% of patients and mainly present as acne-like rash and/or, less frequently, as pruritus, dry skin, desquamation, hypertrichosis, or nail disorders (e.g. paronychia). Approximately 15% of the skin reactions are severe, including single cases of skin necrosis. The majority of skin reactions develop within the first three weeks of therapy. They generally resolve, without sequelae, over time following cessation of treatment if the recommended adjustments in dose regimen are followed (see section 4.4).

Skin lesions induced by cetuximab may predispose patients to superinfections (e.g. with S. aureus), which may lead to subsequent complications, e.g. cellulitis, erysipelas, or, potentially with fatal outcome, staphylococcal scalded skin syndrome or sepsis.

 

Combination treatment

 

When cetuximab is used in combination with chemotherapeutic agents, also refer to their respective product information.

 

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 (see section 4.4).

 

In combination with fluoropyrimidines, 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 fluoropyrimidines.

 

In combination with local radiation therapy of the head and neck area, additional undesirable effects were those typical of radiation therapy (such as mucositis, radiation dermatitis, dysphagia or leukopenia, mainly presenting as lymphocytopenia). In a randomised controlled clinical study with 424 patients, reporting rates of severe acute radiation dermatitis and mucositis as well as of late radiation-therapy-related events were slightly higher in patients receiving radiation therapy in combination with cetuximab than in those receiving radiation therapy alone.

Updated on 10 August 2010 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.4 - Special precautions for storage

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

The following changes apply:

4.2 Posology and method of administration

 

Colorectal cancer

In patients with metastatic colorectal cancer, cetuximab is used in combination with chemotherapy or

as a single agent (see section 5.1). Detection of KRAS mutational status must be performed prior to

the first cetuximab infusion. It is important that a validated test method is used by an experienced

laboratory (see section 4.4 and 5.1).It is recommended that the detection of KRAS mutational status be

performed by an experienced laboratory using a validated test method.

 

4.4 Special warnings and precautions for use

 

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 (non-small cell lung cancer) association

with age ≥ 65 years has been observed. When prescribing cetuximab, the cardiovascular status of the

patients and concomitant administration of cardiotoxic compounds such as fluoropyrimidines should

be taken into account.

Colorectal cancer patients with KRAS mutated tumours

Cetuximab should not be used in the treatment of colorectal cancer patients whose tumours have

KRAS mutations or for whom KRAS tumour status is unknown. Results from clinical studies show a

negative benefit-risk balance in tumours with KRAS mutations.

 

4.5 Interaction with other medicinal products and other forms of interaction

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 (see

section 4.4).

In combination with fluoropyrimidinesinfusional 5-fluorouracil, 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

fluoropyrimidinesinfusional 5-fluorouracil.

 

4.8 Undesirable effects

 

Combination treatment

When cetuximab is used in combination with chemotherapeutic agents, also refer to their respective

product information.

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 (see

section 4.4).

In combination with fluoropyrimidinesinfusional 5-fluorouracil, 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

fluoropyrimidinesinfusional 5-fluorouracil.

 

5.1 Pharmacodynamic properties

 

The KRAS status was recognised as predictive factor for the treatment with cetuximab in 4 of the randomised controlled studies. KRAS mutational status was available for 1261 2072 patients. Only in study EMR 62 202-007, an analysis was not possible.

 

Table amended in section 5.1 also.

 

6.4 Special precautions for storage

Store in a refrigerator (2°C – 8°C).

Updated on 1 July 2010 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 6.2 - Incompatibilities
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

2. Qualitative and quantitative composition

Each ml of solution for infusion contains 5 mg cetuximab.

Each vial

 

of 10 ml contains 50 mg cetuximab.

 

Each vial of 20 ml contains 100 mg cetuximab.

Each vial of 50 ml contains 250 mg cetuximab.

Each vial of 100 ml contains 500 mg cetuximab.

 

 

 

6.2 Incompatibilities

 

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

A separate infusion line must be used.

10. Date of revision of the text

06/2010

Updated on 20 October 2009 SmPC

Reasons for updating

  • Correction of spelling/typing errors

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

The following errors rectified:

section 4.2: change from 'very first dose' to 'initial dose'

section 4.4: deletion of 'body surface area'

section 4.4: addition of 'below the age of 18 years'

section 4.6: addition of 'for the mother'

section 4.8: change from 'primary' to 'main'

section 10: addition '07/2009'

Updated on 4 September 2009 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Chnage to section 4.8 - Undesirable Effects

Severe infusion-related reactions may commonly occur, in rare cases with fatal outcome. They usually develop during or within 1 hour of the initial cetuximab infusion, but may occur after several hours or with subsequent infusions. Although the underlying mechanism has not been identified, some of these reactions may be anaphylactoid/anaphylactic in nature and may include symptoms such as bronchospasm, urticaria, hypotension increase or decrease in blood pressure, loss of consciousness or shock. In rare cases, angina pectoris, myocardial infarction or cardiac arrest have been observed.

 

Updated on 5 December 2008 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.       Clinical particulars

 

4.1     Therapeutic indications

 

Erbitux is indicated for the treatment of patients with squamous cell cancer of the head and neck

                in combination with radiation therapy for locally advanced disease

                in combination with platinum-based chemotherapy for recurrent and/or metastatic disease.

Updated on 13 August 2008 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

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Only changes to section 4.1 shown:
 
Section 4.1 Therapeutic indications
 
Erbitux is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type metastatic colorectal cancer
- in combination with chemotherapy
- as a single agent in patients who have failed oxaliplatin-and irinotecan-based therapy who are intolerant to irinotecan

Updated on 8 August 2008 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.3 - Shelf life

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

change to section 4.1 only shown:
 
Section 4.1 Therapeutic Indications
 

Erbitux is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type metastatic colorectal cancer

                  in combination with chemotherapy

                  as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who
are intolerant to irinotecan.

Updated on 19 March 2008 SmPC

Reasons for updating

  • Change to section 6.3 - Shelf life
  • Change to section 6.6 - Special precautions for disposal and other handling

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

see changes in bold.

6.3     Shelf life

 

Chemical and physical in-use stability of Erbitux 5 mg/ml has been demonstrated for 48 hours at 25°C, if the solution is prepared as described in section 6.6.

 
 
6.6     Special precautions for disposal and other handling

 

Erbitux 5 mg/ml is compatible

·                with polyethylene (PE), ethyl vinyl acetate (EVA) or polyvinyl chloride (PVC) bags,

·                with polyethylene (PE), polyurethane (PUR), ethyl vinyl acetate (EVA), polyolefine thermoplastic (TP) or 
          polyvinyl chloride (PVC) infusion sets,

· with polypropylene (PP) perfusor syringes.

 

Care must be taken to ensure aseptic handling when preparing the infusion.

 

Erbitux 5 mg/ml must be prepared as follows:


For administration with infusion pump or gravity drip (diluted with sterile sodium chloride 9 mg/ml (0.9%) solution)
: Take an infusion bag of adequate size of sterile sodium chloride 9 mg/ml (0.9%) solution

 

 For administration with infusion pump or gravity drip (undiluted): Calculate the required volume of Erbitux. Take an appropriate sterile syringe (minimum 50 ml) and attach a suitable needle. Draw up the required volume of Erbitux from a vial. Transfer the Erbitux into a sterile evacuated container or bag. Repeat this procedure until the calculated volume has been reached. Connect the infusion line and prime it with Erbitux before starting the infusion. Set and control the rate as explained in section 4.2.

 

Updated on 6 June 2007 SmPC

Reasons for updating

  • New SPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)