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Amifostine Dosage

Applies to the following strength(s): 500 mg

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Usual Adult Dose for:

Additional dosage information:

Usual Adult Dose for Non-Small Cell Lung Cancer

To reduce the cumulative renal toxicity associated with repeated administration of cisplatin: 910 mg/m2 administered once daily as a 15 minute IV infusion, starting 30 minutes prior to chemotherapy.

The 15 minute infusion is better tolerated than more extended infusions. Further reductions in infusion times for chemotherapy regimens have not been systematically investigated.

Patients should be adequately hydrated prior to amifostine infusion and kept in a supine position during the infusion. Blood pressure should be monitored every 5 minutes during the infusion, and thereafter as clinically indicated.

The infusion of amifostine should be interrupted if the systolic blood pressure decreases significantly from the baseline value as listed in the guideline below:
1) baseline systolic blood pressure is <100 mm Hg and decreases by 20 mm Hg during treatment
2) baseline systolic blood pressure is 100-119 mm Hg and decreases by 25 mm Hg during treatment
3) baseline systolic blood pressure is 120-139 mm Hg and decreases by 30 mm Hg during treatment
4) baseline systolic blood pressure is 140-179 mm Hg and decreases by 40 mm Hg during treatment
5) baseline systolic blood pressure is >=180 mm Hg and decreases by 50 mm Hg during treatment

If the blood pressure returns to normal within 5 minutes and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent chemotherapy cycles should be 740 mg/m2.

It is recommended that antiemetic medication, including dexamethasone 20 mg intravenously and a serotonin 5-HT3 receptor antagonist, be administered prior to and in conjunction with amifostine. Additional antiemetics may be required based on the chemotherapy drugs administered.

Usual Adult Dose for Ovarian Cancer

To reduce the cumulative renal toxicity associated with repeated administration of cisplatin: 910 mg/m2 administered once daily as a 15 minute IV infusion, starting 30 minutes prior to chemotherapy.

The 15 minute infusion is better tolerated than more extended infusions. Further reductions in infusion times for chemotherapy regimens have not been systematically investigated.

Patients should be adequately hydrated prior to amifostine infusion and kept in a supine position during the infusion. Blood pressure should be monitored every 5 minutes during the infusion, and thereafter as clinically indicated.

The infusion of amifostine should be interrupted if the systolic blood pressure decreases significantly from the baseline value as listed in the guideline below:
1) baseline systolic blood pressure is <100 mm Hg and decreases by 20 mm Hg during treatment
2) baseline systolic blood pressure is 100-119 mm Hg and decreases by 25 mm Hg during treatment
3) baseline systolic blood pressure is 120-139 mm Hg and decreases by 30 mm Hg during treatment
4) baseline systolic blood pressure is 140-179 mm Hg and decreases by 40 mm Hg during treatment
5) baseline systolic blood pressure is >=180 mm Hg and decreases by 50 mm Hg during treatment

If the blood pressure returns to normal within 5 minutes and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent chemotherapy cycles should be 740 mg/m2.

It is recommended that antiemetic medication, including dexamethasone 20 mg intravenously and a serotonin 5-HT3 receptor antagonist, be administered prior to and in conjunction with amifostine. Additional antiemetics may be required based on the chemotherapy drugs administered.

Usual Adult Dose for Malignant Disease

For reduction of moderate to severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands:
The recommended dose of amifostine is 200 mg/m2 administered once daily as a 3 minute intravenous infusion, starting 15 to 30 minutes prior to standard fraction radiation therapy (1.8-2.0 Gy).

Patients should be adequately hydrated prior to amifostine infusion. Blood pressure should be monitored at least before and immediately after the infusion, and thereafter as clinically indicated.

It is recommended that antiemetic medication be administered prior to and in conjunction with amifostine. Oral 5-HT3 receptor antagonists, alone or in combination with other antiemetics, have been used effectively in the radiotherapy setting.

Renal Dose Adjustments

Data not available.

Liver Dose Adjustments

Data not available.

Precautions

Patients who are hypotensive or in a state of dehydration should not receive amifostine. Patients receiving amifostine at doses recommended for chemotherapy who are taking antihypertensive therapy that cannot be stopped for 24 hours preceding amifostine treatment, should not receive amifostine. Patients should be adequately hydrated prior to amifostine infusion and kept in a supine position during the infusion. Blood pressure should be monitored every 5 minutes during the infusion, and thereafter as clinically indicated. It is important that the duration of the 910 mg/m2 infusion not exceed 15 minutes, as administration of amifostine as a longer infusion is associated with a higher incidence of side effects. For infusion duration less than 5 minutes, blood pressure should be monitored at least before and immediately after the infusion, and thereafter as clinically indicated. If hypotension occurs, patients should be placed in the Trendelenburg position and be given an infusion of normal saline using a separate IV line.

Hypotension may occur during or shortly after amifostine infusion, despite adequate hydration and positioning of the patient Hypotension has been associated with dyspnea, apnea, hypoxia, and in rare cases seizures, unconsciousness, respiratory arrest and renal failure.

The safety of amifostine administration has not been established in patients with preexisting cardiovascular or cerebrovascular conditions such as ischemic heart disease, arrhythmias, congestive heart failure, or history of stroke or transient ischemic attacks. Amifostine should be used with particular care in these and other patients in whom the common amifostine adverse effects of nausea/vomiting and hypotension may be more likely to have serious consequences.

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Dialysis

Data not available.

Other Comments

Amifostine should not be administered in patients receiving definitive radiotherapy, except in the context of a clinical trial, since there are at present insufficient data to exclude a tumor protective effect in this setting.

Antiemetic medication should be administered prior to and in conjunction with amifostine. When amifostine is administered with highly emetogenic chemotherapy, the fluid balance of the patient should be carefully monitored.

Serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome or patients receiving multiple doses of amifostine. If necessary, calcium supplements can be administered.

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