AMIFOSTINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMIFOSTINE (AMIFOSTINE).
Amifostine is a prodrug that is dephosphorylated by alkaline phosphatase to an active free thiol metabolite, which scavenges free radicals generated by chemotherapy and radiation therapy, thereby protecting normal tissues from cytotoxic damage.
| Metabolism | Amifostine is rapidly dephosphorylated by alkaline phosphatase to the active free thiol metabolite (WR-1065) and further metabolized to disulfides. |
| Excretion | Primarily renal; unchanged drug and metabolites (70-90% of administered dose recovered in urine within 24 hours). Biliary/fecal excretion negligible (<5%). |
| Half-life | Terminal elimination half-life approximately 8-9 minutes for the parent compound; active metabolite (WR-1065) has a half-life of about 1-2 hours. Clinical context: short half-life allows administration just before chemotherapy or radiation. |
| Protein binding | Low protein binding; approximately 10-15% bound, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 6-10 L/kg, indicating extensive tissue distribution (likely due to rapid cellular uptake). |
| Bioavailability | Not applicable; only administered intravenously (oral bioavailability negligible due to extensive first-pass metabolism). |
| Onset of Action | Intravenous: Radioprotective effect occurs within 1-2 minutes; chemoprotective effect begins within 15 minutes of infusion start. |
| Duration of Action | Radioprotection lasts 2-3 hours after infusion; chemoprotection spans 4-6 hours. Clinical note: Infusion must be timed immediately prior to treatment. |
910 mg/m² IV over 15 minutes, once daily, 30 minutes prior to chemotherapy or radiotherapy.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >60 mL/min: no adjustment; CrCl 30-60 mL/min: reduce dose by 25%; CrCl <30 mL/min: reduce dose by 50%; not recommended if CrCl <10 mL/min. |
| Liver impairment | No specific dose adjustments for hepatic impairment; use with caution in severe hepatic dysfunction. |
| Pediatric use | Not established; limited data suggest 740 mg/m² IV over 15 minutes prior to chemotherapy. |
| Geriatric use | No specific dose adjustments; monitor for hypotension and electrolyte disturbances. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AMIFOSTINE (AMIFOSTINE).
| Breastfeeding | Not known if excreted in human milk. Animal data not available. Due to potential for serious adverse reactions (e.g., hypotension, hypocalcemia) in nursing infants, advise against breastfeeding during therapy and for at least 1 week after last dose. No M/P ratio available. |
| Teratogenic Risk | Pregnancy Category D. Animal studies have shown teratogenicity (skeletal and visceral malformations) at doses lower than human therapeutic doses. In humans, aminofostine is used as a cytoprotectant during chemotherapy; limited human data exist but due to its active metabolite and potential to cause fetal harm, use only if clearly needed. First trimester exposure may be associated with increased risk of malformations; second and third trimester use may cause fetal toxicity (e.g., hypotension, hypocalcemia). Women of childbearing potential should use effective contraception. |
■ FDA Black Box Warning
Patients should be monitored for hypotension and severe allergic reactions (e.g., cutaneous reactions, anaphylaxis). Amifostine should be administered only when a physician is immediately available to treat these reactions. Patients should be adequately hydrated before administration.
| Serious Effects |
["Known hypersensitivity to amifostine or any of its components","Patients who are hypotensive or dehydrated"]
| Precautions | ["Hypotension: Blood pressure monitoring required during administration; interrupt infusion if significant hypotension occurs","Severe cutaneous reactions: Including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis; discontinue permanently if suspected","Hypersensitivity: Anaphylactic reactions may occur; have appropriate resuscitation equipment available","Nausea and vomiting: Antiemetic therapy recommended prior to administration","Hypocalcemia: Monitor calcium levels in patients at risk"] |
| Food/Dietary | No known food interactions. However, maintain adequate hydration. Avoid alcohol as it may exacerbate hypotension. |
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| Fetal Monitoring | Monitor maternal blood pressure (every 5 minutes during infusion for hypotension), serum calcium (risk of hypocalcemia), and electrolytes. Fetal monitoring: consider fetal heart rate monitoring if used near term due to potential for fetal hypotension. Assess fetal growth and well-being with ultrasound if prolonged use. |
| Fertility Effects | Animal studies have shown impaired fertility (reduced pregnancy rates, increased preimplantation loss) at doses comparable to human doses. In males, sperm motility and count may be reduced. Reversible upon discontinuation in animal models; human data limited. |
| Clinical Pearls | Amifostine is a cytoprotective agent used to reduce the cumulative renal toxicity of cisplatin and the incidence of xerostomia in patients undergoing radiation therapy for head and neck cancer. It is a prodrug that is dephosphorylated by alkaline phosphatase to an active thiol metabolite that scavenges free radicals. Administer intravenously over 15 minutes, starting 30 minutes prior to chemotherapy or radiation. Monitor blood pressure closely during infusion due to risk of hypotension; hold infusion if systolic BP drops significantly. Antiemetic premedication (e.g., dexamethasone, 5-HT3 antagonist) is recommended as nausea and vomiting are common. Avoid use in patients with pre-existing hypotension, dehydration, or those on antihypertensives. Calcium supplementation may be needed due to transient hypocalcemia from chelation. |
| Patient Advice | You will receive this medication as an intravenous infusion before your chemotherapy or radiation treatment. · Common side effects include nausea, vomiting, and low blood pressure. You will be monitored for blood pressure changes during the infusion. · Report any dizziness, lightheadedness, or fainting immediately. · You may be given medications to prevent nausea and vomiting before each dose. · Stay well-hydrated before and after treatment. · Inform your healthcare provider if you have a history of low blood pressure, dehydration, or are taking blood pressure medications. · This drug may temporarily lower calcium levels; notify your doctor if you experience muscle cramps or tingling in your fingers or around your mouth. |