Ethyol


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amifostine

Ethyol

Pharmacologic class: Organic thiophosphate cytoprotective drug

Therapeutic class: Cytoprotectant

Pregnancy risk category C

Action

Undergoes conversion to free thiol, an active metabolite that reduces toxic effects of cisplatin on renal tissue

Availability

Powder for injection: 500-mg anhydrous base and 500 mg mannitol in 10-ml vials

Indications and dosages

To reduce cumulative renal toxicity of cisplatin therapy in patients with ovarian cancer or non-small-cell lung

Adults: 910 mg/m2 I.V. daily as a 15-minute infusion, starting 30 minutes before chemotherapy

To reduce moderate to severe xerostomia in patients undergoing postoperative radiation treatment for head or neck cancer

Adults: 200 mg/m2 I.V. daily as a 3-minute infusion, starting 15 to 30 minutes before standard fraction radiation therapy

Off-label uses

• Protection against cisplatin- and paclitaxel-induced neurotoxicity

Contraindications

• Hypersensitivity to drug
• Hypotension

Precautions

Use cautiously in:
• arrhythmias, heart failure, ischemic heart disease, renal impairment, hearing impairment, hypocalcemia, myasthenia gravis, nausea, vomiting, hypotension, obesity
• history of cerebrovascular accident or transient ischemic attacks
• concurrent antihypertensive therapy that can't be discontinued for 24 hours before amifostine therapy (not recommended)
• definitive radiotherapy (not recommended)
• elderly patients
• pregnant patients (safety and efficacy not established)
• breastfeeding patients
• children (safety and efficacy not established).

Administration

• Ensure that patient is adequately hydrated before starting drug.
• Give antiemetics before and during therapy.
• Reconstitute single-dose vial with 9.7 ml of sterile normal saline injection. May be further diluted with normal saline solution up to a concentration of 40 mg/ml.
• Don't mix with other drugs or solutions.
• Know that drug also can be prepared in polyvinyl chloride bags.
• Don't infuse longer than 15 minutes; doing so increases risk of adverse reactions.

Keep patient supine during administration.

Adverse reactions

CNS: dizziness, drowsiness, rigors

CV: hypotension

GI: nausea, vomiting

Metabolic: hypocalcemia

Respiratory: dyspnea, sneezing

Skin: flushing, rash, urticaria, erythema multiforme

Other: chills, warm sensation, hiccups, allergic reactions

Interactions

Drug-drug.Antihypertensives: increased risk of hypotension

Drug-diagnostic tests.Calcium: decreased level

Patient monitoring

• Monitor blood pressure every 5 minutes during infusion and immediately after infusion as clinically indicated.
• Assess for severe nausea and vomiting.
• Monitor fluid intake and output.
• Monitor blood calcium level. Give calcium supplements as ordered.

Patient teaching

• Emphasize importance of remaining supine during drug administration to prevent hypotension.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
• Provide dietary counseling. Refer patient to dietitian if adverse GI effects significantly limit food intake.
• Inform patient that sneezing is a normal effect of drug.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

amifostine

(a-mi-fos-teen) ,

Ethyol

(trade name)

Classification

Therapeutic: cytoprotective agents
Pregnancy Category: C

Indications

Reduces renal toxicity from cisplatin.Reduces the incidence of moderate to severe xerostomia from postoperative radiation for head and neck cancer in which the radiation port includes a large portion of the parotid glands.

Action

Converted by alkaline phosphatase in tissue to a free thiol compound that binds and detoxifies damaging metabolites of cisplatin and reactive oxygen species generated by radiation.

Therapeutic effects

Decreased renal damage from cisplatin.
Decreased severity of xerostomia following radiation for head and neck cancer.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Rapidly cleared from plasma; converted to cytoprotective compounds by alkaline phosphatase in tissues.
Half-life: 8 min.

Time/action profile

ROUTEONSETPEAKDURATION
IVunknownunknownunknown

Contraindications/Precautions

Contraindicated in: Known sensitivity to aminothiol compounds;Hypotension or dehydration; Lactation: Use an alternative to breast milk;Concurrent antineoplastic therapy for other tumors (especially malignancies of germ cell origin).
Use Cautiously in: Obstetric / Pediatric: Safety not established; Geriatric: Geriatric patients or patients with cardiovascular disease have ↑ risk of adverse reactions.

Adverse Reactions/Side Effects

Central nervous system

  • dizziness
  • somnolence

Ear, Eye, Nose, Throat

  • sneezing

Cardiovascular

  • hypotension (most frequent)

Gastrointestinal

  • hiccups
  • nausea (most frequent)
  • vomiting (most frequent)

Dermatologic

  • flushing

Fluid and Electrolyte

  • hypocalcemia

Miscellaneous

  • allergic reactions including anaphylaxis, stevens-johnson syndrome, toxic epidermal necrolysis, toxoderma, erythema multiforma, exfoliative dermatitis (↑ when used as a radioprotectant) (life-threatening)
  • chills

Interactions

Drug-Drug interaction

Concurrent use of antihypertensives ↑ risk of hypotension.

Route/Dosage

Reduction of Renal Damage with Cisplatin

Intravenous (Adults) 910 mg/m2 once daily, within 30 min before chemotherapy; if full dose is poorly tolerated, subsequent doses should be ↓ to 740 mg/m2.

Reduction of Xerostomia from Radiation

Intravenous (Adults) 200 mg/m2 once daily, as a 3-minute infusion starting 15–30 min before standard fraction radiation therapy.

Availability (generic available)

Powder for injection: 500 mg/vial

Nursing implications

Nursing assessment

  • Monitor BP before and every 5 min during infusion. Discontinue antihypertensives 24 hr prior to treatment. If significant hypotension requiring interruption of therapy occurs, place patient in Trendelenburg position and administer an infusion of 0.9% NaCl using a separate IV line. If BP returns to normal in 5 min and patient is asymptomatic, infusion may be resumed so that full dose may be given.
  • Assess fluid status before administration. Correct dehydration before instituting therapy. Nausea and vomiting are frequent and may be severe. Administer prophylactic antiemetics including dexamethasone 20 mg IV and a serotonin-antagonist antiemetic (dolasetron, granisetron, ondansetron, palonosetron) before and during infusion. Monitor fluid status closely.
  • Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue the drug and notify physician or other health care professional immediately if these problems occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction.
  • Xerostomia: Assess patient for dry mouth and mouth sores periodically during therapy.
  • Monitor patient for skin reactions before, during, and after amifostine administration; reactions may be delayed by several weeks after initiation of therapy. Permanently discontinue amifostine in patients who experience serious or severe cutaneous reactions or cutaneous reactions associated with fever or other symptoms of unknown cause. Withhold therapy and obtain dermatologic consultation and biopsy for cutaneous reactions or mucosal lesions of unknown cause appearing outside of injection site or radiation port, and for erythematous, edematous, or bullous lesions on the palms of the hand or soles of the feet.
  • Lab Test Considerations: Monitor serum calcium concentrations before and periodically during therapy. May cause hypocalcemia. Calcium supplements may be necessary.

Potential Nursing Diagnoses

Risk for injury (Indications)

Implementation

  • Intravenous Administration
  • pH: 7.0.
  • Intermittent Infusion: Diluent: Reconstitute with 9.7 mL of sterile 0.9% NaCl. Dilute further with 0.9% NaCl. Do not administer solutions that are discolored or contain particulate matter. Solution is stable for 5 hr at room temperature or 24 hr if refrigerated.Concentration: Adults: dilute dose to a final volume of 50 mL; Children: 5–40 mg/mL.
  • Rate: For renal toxicity: Administer over 15 min within 30 min before chemotherapy administration. Longer infusion times are not as well tolerated. For xerostomia: Administer over 3 min starting 15–30 min prior to radiation therapy.
  • Y-Site Compatibility: amikacin, aminophylline, amphotericin B liposome, ampicillin, ampicillin/sulbactam, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, caspofungin, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daptomycin, daunorubicin hydrochloride, dexamethasone, dexmedetomidine, diltiazem, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin hydrochloride, doxycycline, droperidol, enalaprilat, epirubicin, ertapenem, etoposide, etoposide phosphate, famotidine, fenoldopam, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gemcitabine, gentamicin, granisetron, haloperidol, heparin, hydrocortisone, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, leucovorin, levofloxacin, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, mesna, methotrexate, methylprednisolone, metoclopramide, metronidazole, milrinone, mitomycin, morphine, nalbuphine, nesiritide, octreotide, ondansetron, oxaliplatin, paclitaxel, palonosetron, pantoprazole, pemetrexed, piperacillin/tazobactam, potassium chloride, promethazine, ranitidine, rituximab, sodium acetate, sodium bicarbonate, streptozocin, tacrolimus, teniposide, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, trastuzumab, trimethoprim/sulfamethoxazole, vancomycin, vasopressin, vecuronium, vinblastine, vincristine, vinorelbine, voriconazole, zidovudine
  • Y-Site Incompatibility: acyclovir, amphotericin B colloidal, cefoperazone, cisplatin, ganciclovir, hydroxyzine, minocycline, prochlorperazine, quinupristin/dalfopristin
  • Additive Incompatibility: Do not mix with other solutions or medications.

Patient/Family Teaching

  • Explain the purpose of amifostine infusion to patient.
  • Inform patient that amifostine may cause hypotension, nausea, vomiting, flushing, chills, dizziness, somnolence, hiccups, and sneezing.
  • Advise patient to notify health care professional if skin reactions occur.

Evaluation/Desired Outcomes

  • Prevention of renal toxicity associated with repeated administration of cisplatin in patients with ovarian cancer.
  • Decreased severity of xerostomia from radiation treatment of head and neck cancer.

Ethyol

A brand name for AMIFOSTINE.
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Clinigen's product lines increased from three to five following the acquisition of two oncology support products: Savene in March and Ethyol from AstraZeneca in August.
Clinigen declared the purchase of Ethyol from AstraZeneca, which will see it assume full responsibility for distribution of the product.
April 18, 2012 /PRNewswire/ --Pinnacle Biologics is pleased to announce the appointment of Bioprojet Pharma, effective March 15, 2012, as its exclusive distributor for ETHYOL (amifostine) and PHOTOFRIN (Porfimer Sodium) in select European countries.
Detroit, MI) has executed a settlement agreement with MedImmune, stipulating the dismissal of the lawsuits filed in the United States District Court for the District of Maryland regarding the submission of an Abbreviated New Drug Application (ANDA) for a generic version of Ethyol.
1million over a potential generic threat to cancer treatment Ethyol.
Evoxac (cevimeline/Daiichi Sankyo) is approved in the US and Japan to treat xerostomia associated with Sjogren's syndrome, while Ethyol (amifostine/MedImmune) is approved in the US and Europe for xerostomia associated with radiation therapy.
Currently Pinnacle commercializes ETHYOL, brand of Amifostine in Western Europe.
Detroit, MI) announced that it has executed a settlement agreement with MedImmune, stipulating the dismissal of the lawsuits filed in the United States District Court for the District of Maryland regarding the submission of an Abbreviated New Drug Application (ANDA) for a generic version of Ethyol.
NYSE Amex: CPD) announces today that it has executed a settlement agreement with MedImmune, stipulating the dismissal of the lawsuits filed in the United States District Court for the District of Maryland regarding the submission of an Abbreviated New Drug Application (ANDA) for a generic version of Ethyol .
stated, "We are pleased to conclude this agreement with pharmexx, which allows us a cost effective way to support our sales and marketing activities for Ethyol (R) in key European markets where we believe there is upside potential.
the main products are synagis, cytogam, respigam, ethyol, neutrexin and hexalen.
The agreement, which is scheduled to take effect on June 1, 2008, grants Pinnacle Biologics exclusive Ethyol marketing authorization, certain licenses and distribution rights in Western Europe, Turkey and Israel.