Ethyol

Mechanism of Action

Provide the protection your patients need

  • Treatment-induced toxicities may be due, at least in part, to oxidative damage to a cell’s DNA and the resulting cell death12,13
  • An effective cytoprotector should12,13
    • Be selective for healthy tissue13
    • Act by directly or indirectly preventing DNA damage caused by free radicals12
    • Not compromise the efficacy of the planned tumor treatment13

ETHYOL® (amifostine) is a prodrug that preferentially protects normal tissue against chemo- and radiotherapy toxicities1

The cytoprotective effects of ETHYOL are based on its preferential uptake into normal tissues – with concentrations that may be 100-fold greater than in tumor tissues14,16

  • ETHYOL is a very hydrophilic compound that is rapidly dephosphorylized to an active free thiol metabolite1
  • Once inside the cell, the active thiol, WR-1065, scavenges free radicals and protects cellular membranes and DNA from damage – with additional actions adding to its protective effects16
    • ETHYOL enhances cellular proliferation that results in less DNA damage, which may be an important pathway to accelerated recovery of endothelial tissues
    • ETHYOL, indirectly through hypoxia, may upregulate the expression of proteins involved with DNA repair and inhibition of apoptosis
  • ETHYOL and its metabolites display prolonged retention within the normal tissue14

References
1. ETHYOL [prescribing information]. Nashville, TN; Cumberland Pharmaceuticals Inc.; May 2017. 12. Mell LK, Movsas B. Pharmacologic normal tissue protection in clinical radiation oncology: focus on amifostine. Expert Opin Drug Metab Toxicol. 2008;4(10):1341-1350. 13. Santini V, Giles FJ. The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica. 1999; 84(11): 1035-1042. 14. Capizzi RL, Scheffler BJ, Schein PS. Amifostine-mediated protection of normal bone marrow from cytotoxic chemotherapy. Cancer. 1993;72(11 suppl):3495-3501. 15. Moss RW. Should patients undergoing chemotherapy and radiotherapy be prescribed antioxidants? Int Cancer Ther. 2006;5(1):63-82. 16. Kouvaris JR, Kouloulias VE, Vlahos LJ. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist. 2007;12(6):738-747.

Indication: ETHYOL (amifostine) is indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer.

ETHYOL is indicated to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands.

IMPORTANT DOSAGE AND ADMINISTRATION INSTRUCTIONS
Patients should be adequately hydrated prior to ETHYOL infusion. Blood pressure should be monitored prior to, during and immediately after infusion. Antiemetic medication should be administered prior to and in conjunction with ETHYOL.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS

ETHYOL is contraindicated in patients with known hypersensitivity to aminothiol compounds.

WARNINGS AND PRECAUTIONS
ETHYOL should not be administered in patients receiving chemotherapy for other malignancies in which chemotherapy can produce a significant survival benefit or cure. ETHYOL should not be administered in patients receiving definitive radiotherapy, since there are at present insufficient data to exclude a tumor-protective effect in this setting.

Patients who are hypotensive or in a state of dehydration should not receive ETHYOL. Patients should have antihypertensive therapy interrupted 24 hours preceding administration of ETHYOL. Patients should not receive ETHYOL where therapy cannot be stopped for 24 hours preceding treatment.

The fluid balance of the patient should be carefully monitored when ETHYOL is administered with highly emetogenic chemotherapy.

Fatal and serious cutaneous reactions such as Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, toxicoderma, exfoliative dermatitis and drug reaction with biopsy-confirmed eosinophilia and systemic symptoms (DRESS) have been reported with ETHYOL treatment. These reactions is higher in patients receiving ETHYOL as a radioprotectant. Serious cutaneous reactions may develop weeks after initiation of ETHYOL administration. Discontinue Ethyol for cutaneous reactions or mucosal lesions appearing outside the injection site or radiation port and for erythematous, edematous or bullous lesions on the palms or soles. Monitor patients carefully prior to, during and after ETHYOL administration. In case of severe acute allergic reactions ETHYOL should be immediately and permanently discontinued. Epinephrine and other appropriate measures should be available for treatment of serious allergic events such as anaphylaxis.

ADVERSE REACTIONS
In a randomized study of patients with ovarian cancer given ETHYOL, the most common adverse events included transient hypotension, nausea, vomiting, and a decrease in serum calcium concentrations. Other adverse events reported in clinical studies involving patients with ovarian or head and neck cancers include hypersensitivity and anaphylactic reactions, flushing, chills, malaise, pyrexia, diplopia, blurred vision, rash, dizziness, somnolence, hiccups, diarrhea, and sneezing. Injection site reactions including pruritus and urticaria were also observed.

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