Important information regarding Ethyol (amifostine) and severe cutaneous reactions - Health Professional Advisory

Date: 2003-03-12

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The Marketed Health Products Directorate (MHPD), Therapeutic Products Directorate (TPD) and Biologics and Genetic Therapies Directorate (BGTD) post safety alerts, public health advisories, press releases and other notices as a service to health professionals, consumers, and other interested parties. Although MHPD, TPD and BGTD approve therapeutic products, MHPD, TPD and BGTD do not endorse either the product or the company. Any questions regarding product information should be discussed with your health professional.

This is a letter issued by the Marketed Health Products Directorate and the Therapeutic Products Directorate

March 12, 2003

The Marketed Health Products and Therapeutic Products Directorates wish to draw your attention on a letter to prescribers published on February 10th 2003 by the Agence française de sécurité sanitaire des produits de santé (Afssaps) regarding important information on the use of amifostine (marketed as Ethyol in Canada).

The original French posting is available at:  http://afssaps.sante.fr/htm/10/filltrpsc/ltrpsc03.htm - available in French only

AGENCE FRANÇAISE DE SECURITÉ SANITAIRE DES PRODUITS DE SANTÉ

IMPORTANT SAFETY INFORMATION regarding Ethyol® (amifostine) and severe cutaneous reactions

Dear healthcare professional:

Ethyol® is a proprietary medicine produced by MedImmune Oncology Inc. and distributed by Schering-Plough within the European Union.

Working in consultation with the Agence française de sécurité sanitaire des produits de santé (Afssaps), MedImmune Oncology Inc. and Schering-Plough wish to apprise you of important safety information concerning Ethyol® (amifostine) and to make certain recommendations concerning the management of severe cutaneous reactions.

The therapeutic indications for Ethyol® (amifostine) are:

IN CHEMOTHERAPY

• to prevent the risk of neutropenia and its consequences (infections in particular) resulting from the combined use of cyclophosphamide and cisplatin in patients with advanced ovarian carcinoma (IFGO stage III or IV);
  
  
• to prevent cumulative renal toxicity associated with the administration of cisplatin and treatments containing cisplatin, when unit doses of the latter are between 60 and 120 mg/m2, in association with measures to provide adequate hydration to patients presenting advanced non-germinal solid tumors.

IN RADIOTHERAPY

• to prevent acute and late xerostomia in ORL cancer patients, in association with standard fractionated radiotherapy.

Since 1994, the date Ethyol® was authorized for marketing in Europe, approximately 128,000 patients have been treated with Ethyol® in Europe and around the world. Approximately 32,000 of these patients were given Ethyol® in the context of radiation protection measures.

During the past two years, an increased number of cutaneous reactions has been reported with Ethyol®, at the same time as its use has become more widespread, particularly in the context of radiation treatment. A total of 35 cases of severe cutaneous reactions (24 radiotherapy-related) have been reported around the world since Ethyol® came onto the market. These include cases of polymorphic erythema (8), Stevens-Johnson syndrome (10), toxic epidermal necrolysis (11), toxidermia (3), and bullous erythema (3). Four of these cases had a fatal outcome. The notification rate for severe cutaneous reactions with Ethyol® is estimated to be 6 to 9 cases per 10,000 in patients undergoing radiation treatment and 0.8 to 1 case per 10,000 in patients receiving chemotherapy. For 10 of the 35 reported cases, it would appear that administration of Ethyol® was continued despite the appearance of warning signs and symptoms of a cutaneous nature.

In keeping with their common commitment to ensure patient safety, MedImmune Oncology Inc. and Schering-Plough, in consultation with Afssaps, is informing health practitioners of the risk of cutaneous reactions and recommending strategies to manage such reactions should they arise.

Recommendations for the management of skin reactions associated with Ethyol®

• The patient should be evaluated from a cutaneous standpoint before each dose of Ethyol® is administered, with particular attention to the potential occurrence of the following events:

  • any rash appearing near the mouth or mucous membranes for which no other etiology can be established (such as radiation-induced mucitis, herpes simplex, etc.)
  • erythematous, edematous or bullous lesions on the palms of the hands or the soles of the feet and/or truncal cutaneous reactions (anterior trunk, posterior trunk, abdomen)
    cutaneous reactions associated with fever or other general signs.
    
    

• Cutaneous reactions must be clearly differentiated from radiation-induced dermatitis and cutaneous reactions of other etiology.
  

• In the presence of a cutaneous reaction which appears at a distance from the injection site or the irradiated areas and has no other etiology, the administration of Ethyol® should be discontinued and a consultation with a dermatologist, as well as a biopsy, should be considered.
  

• Cutaneous reactions should be treated symptomatically. The resumption of treatment with Ethyol® is a medical decision which should be based on appropriate clinical evaluations and dermatological consultations.
  

• Ethyol® should be stopped permanently in the presence of any cutaneous reaction considered to be polymorphic erythema, toxic epidermal necrolysis, Stevens-Johnson syndrome, or exfoliative dermatitis, as well as any cutaneous reaction associated with fever or other general signs which cannot be attributed to some other etiology.

Please report any undesirable side effect you may encounter to the Centre régional de pharmacovigilance (CRPV) with which you deal (contact information available on the website of Afssaps: www.afssaps.sante.fr or in the front pages of the Vidal dictionary).

If you have any questions or wish to obtain additional information concerning the use of Ethyol® please contact the Unité de Pharmacovigilance (01 41 06 36 36) or the Unité d'Information Médicale at Schering-Plough (01 55 46 44 80).

Sincerely,

original signed by

Dr. Alain RIMAILHO
Medical director

Any suspected adverse reactions can also be reported to:
Canadian Adverse Drug Reaction Monitoring Program (CADRMP)
Marketed Health Products Directorate
HEALTH CANADA
Address Locator: 0201C2
OTTAWA, Ontario, K1A 1B9
Tel: (613) 957-0337 or Fax: (613) 957-0335
Toll free for consumers and health professionals:
Tel: 866 234-2345, Fax: 866 678-6789
cadrmp@hc-sc.gc.ca

The AR Reporting Form and the AR Guidelines can be found on the TPD web site or in The Canadian Compendium of Pharmaceuticals and Specialties.