Systemic Therapy Program

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Drug Monographs
Treatment Regimens

Scientific Name:
AMIFOSTINE
Brand Name(s):
Ethyol®

Drug Monograph

Pharmacology

Mechanism of Action

Prodrug; pharmacologically active free thiol metabolite can reduce the toxic effects of cisplatin (is available to bind to , and detoxify, reactive metabolites of cisplatin). It can also act as a scavenger of free radicals that may be generated in tissues exposed to cisplatin. It also protects against cell damage from radiation and other alkylators. Other mechanisms may be responsible for protection against paclitaxel toxicity and for therapeutic effect in MDS.

Pharmacokinetics

Oral Absorption:
poor
Distribution:
In bone marrow cells after 4-8 minutes; t½ less than 1 minutes; excretion in breast-milk unknown
Cross blood brain barrier?  No information
Vd: 3.5 L
PPB: no
Metabolism:
Prodrug is metabolized by hepatic alkaline phosphatase (dephosphorylation)
metabolite(s): 2 active metabolites: thiol metabolite, disulfide metabolite (less active)
Excretion:
renal
urine: unchanged 69%, disulfide 2.2%
t½: 8 minutes
Cl: 2.17 L/min

Side Effects

IMMEDIATE ONSET (hours to days)

hypotension (62%)
nausea, vomiting (may be severe)
• dehydration
• allergic reactions (rare)

EARLY ONSET (days to weeks)

• decreased serum calcium

Therapeutics

Approved Indications

Reduction of cumulative renal toxicity associated with repeated doses of cisplatin.

Routes

• Intravenous infusion (over 15 min) or rapid intravenous injection- 15-20 minutes before chemotherapy.
• Infusion over 3 minutes before radiotherapy.

Administration

• Mix in 100mL minibag (Normal Saline) ; Infuse over 15 minutes
• Patient must be supine during infusion; measure blood pressure throughout infusion

IV Compatibility

0.9% sodium chloride (ONLY)

Dosing

Intravenous:

• 910mg/m2 starting 30 minutes prior to chemotherapy- Infuse over 15 minutes (longer infusions are less well tolerated)
• Retreatment with 740mg/m2 starting 30 minutes prior to chemotherapy (if 910mg/m2 not tolerated in previous dose- Infuse over 15 minutes
• 200mg/m2 daily during radiation therapy (for reduction of xerostomia from head & neck radiation- Infuse over 3 minutes

Pediatric: Limited data on the use of this drug in pediatric patients

Antiemetic Risk

HIGH RISK (30-90% of patients)
• If not already in use for chemotherapy, use a serotonin receptor antagonist PLUS dexamethasone pre-chemotherapy and post-chemotherapy

Contraindications

Hypotensive patients, patients reseaving antihypertensive therapy, sensitivity to aminothiol compounds or mannitol.

Monitoring

Clinical Monitoring

RECOMMENDED CRITERIA
• Blood pressure monitoring through infusion; interrupt infusion if hypotensive, administer Normal Saline until normotensive, then restart Amifostine infusion

SUGGESTED CRITERIA

• Serum calcium levels, especially if symptomatic or at high risk for hypocalcemia

Extravasation Hazard

None

Significant Interactions

Bleomycin, carboplatin, cisplatin, fluorouracil, paclitaxel, antihypertensives hypotension-producing medications.

Product Information

Commercial Product Description

Vial of 500mg Amifostine for reconstitution with 9.7mL sterile Saline Injection. May be available on a case-by-case basis through Special Access Program, Health Canada (call 613-941-2108 /e-mail EDR_Drugs-BPA@hc-sc.gc.ca.

Pharmaceutical Considerations

Injection:
Vials with 500mg of amifostine for reconstitution.  Store at room temperature 20-25oC

Preparation
:
Reconstitute with 9.7mL of sterile normal saline, for a final solution of 500mg/10mL. 

Reconstituted Solution for Injection
:
Solution is stable for up to 5 hours at room temperature or 24 hours under refrigeration.

Diluted Solution for Infusion
:
Dilute measured dose in normal saline to t final concentration of 5-40mg/mL.  Diluted solution is stable for up to 5 hours at room temperature or 24 hours under refrigeration.

Handling Risk Level

Pregnancy CPOSSIBLE HAZARDOUS DRUG
FDA Pregnancy Risk Factor C

  • Consider handling this drug using precuations outlined in CCNS Policies for Occupational Safety, Preparing Cancer Chemotherapy and Administering Cancer Chemotherapy

Note

HANDLING RISK LEVEL:

HAZARD RISK LEVEL 3
FDA Pregnancy Risk Factor C
• Consider handling this drug using precuations outlined in CCNS Policies for Preparing Cancer Chemotherapy and Administering Cancer Chemotherapy
• Go to "Additional Information" tab (above) for links to CCNS Policies

Availability & Funding

Administrative Information (Nova Scotia)

• CCNS Provincial Formulary Status- Advanced Level Non-Formulary status • Go to "Additional Information" tab (above) for links to Provincial Formulary of Cancer Drugs Pharmacare Formulary Status: Non-Formulary



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