Davis's Drug Guide

amifostine

General

Pronunciation
a-mi-FOS-teen

Trade Name(s)

• Ethyol



Pregnancy Category
Category C

Ther. class.
cytoprotective agents

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 Effect(s):

• 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

Contraindication/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:

OB: Safety not established

Geri: Geriatric patients or patients with cardiovascular disease have increased risk of adverse reactions

Adverse Reactions/Side Effects

CNS: dizziness, somnolence.

EENT: sneezing.

CV: hypotension.

GI: hiccups, nausea, vomiting.

Derm: flushing.

F and E: hypocalcemia.

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, TOXODERMA, ERYTHEMA MULTIFORMA, EXFOLIATIVE DERMATITIS (I WHEN USED AS A RADIOPROTECTANT), chills.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug
Concurrent use of antihypertensives risk of hypotension

Route/Dosage

Reduction of Renal Damage with Cisplatin

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



Reduction of Xerostomia from Radiation

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

Availability

Powder for injection: 500 mg/vial

Assessment

• Monitor blood pressure 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 blood pressure 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 (ondansetron, dolasetron, granisetron, 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



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

IV Adminstration:

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

» ampicillin

» ampicillin/sulbactam

» aztreonam

» bleomycin

» bumetanide

» buprenorphine

» butorphanol

» calcium gluconate

» carboplatin

» carmustine

» cefazolin

» cefotaxime

» cefotetan

» cefoxitin

» ceftazidime

» ceftizoxime

» ceftriaxone

» cefuroxime

» cimetidine

» ciprofloxacin

» clindamycin

» cyclophosphamide

» cytarabine

» dacarbazine

» dactinomycin

» daunorubicin

» diphenhydramine

» dobutamine

» docetaxel

» dopamine

» doxorubicin

» doxycycline

» droperidol

» enalaprilat

» etoposide

» famotidine

» floxuridine

» fluconazole

» fludarabine

» fluorouracil

» furosemide

» gentamicin

» gemcitabine

» granisetron

» haloperidol

» heparin

» hydrocortisone

» hydromorphone

» idarubicin

» ifosfamide

» imipenem/cilastatin

» leucovorin

» lorazepam

» magnesium sulfate

» mannitol

» mechlorethamine

» meperidine

» mesna

» methotrexate

» methylprednisolone

» metoclopramide

» metronidazole

» mitomycin

» mitoxantrone

» morphine

» nalbuphine

» ondansetron

» pemetrexed

» piperacillin

» potassium chloride

» promethazine

» ranitidine

» sodium bicarbonate

» streptozocin

» teniposide

» thiotepa

» ticarcillin/clavulanate

» tobramycin

» trimethoprim/sulfamethoxazole

» trimetrexate

» vancomycin

» vinblastine

» vincristine

» zidovudine

Y-Site Incompatibility:

» acyclovir

» amphotericin B

» cefoperazone

» chlorpromazine

» cisplatin

» ganciclovir

» prochlorperazine

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

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



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