Amifostine (WR-2721, ethiofos) is a phosphorylated sulfhydryl-containing prodrug that protects tissues from the cytotoxic actions of radiation and chemotherapy. It was originally developed by the military for use as a radioprotectant in the event of nuclear warfare. Amifostine has selective cytoprotective effects for normal tissues. In the pivotal US trial, amifostine reduced the incidence and severity of myelosuppression, nephrotoxicity and peripheral neuropathies seen with cisplatin and cyclophosphamide combination therapy. Studies examining the myeloprotective effects of amifostine show a higher white blood cell nadir, shorter duration of neutropenia, and a decreased incidence of neutropenia-related adverse events as compared to controls. These chemoprotective effects seem to be additive with repeated cycles and do not affect antitumor efficacy. Preliminary trials indicate enhanced response rates but no effect on survival in patients treated with radiation and amifostine. In head and neck cancer patients, amifostine administered prior to radiation therapy significantly reduced the incidence of acute- and late-onset xerostomia as compared to patients who received radiation alone. Amifostine is being studied to see if it is efficacious at preventing toxicities due to paclitaxel, melphalan and mitomycin-C in pediatric patients. Initial studies have shown that treatment with amifostine may increase platelet, red blood cell, and neutrophil counts and decrease transfusion requirements in patients with myelodysplastic syndromes. Amifostine has been in use in Europe since 1994. Amifostine was FDA-approved on December 8, 1995 for prevention of cisplatin-induced nephrotoxicity in ovarian cancer patients and in March 1996 was given FDA approval for use in patients with non-small cell lung cancer receiving cisplatin based chemotherapy; this indication was removed in April 2006. In June 1998, the FDA designated Ethyol as an orphan drug for reducing the incidence and severity of radiation-induced xerostomia. In June 1999, the FDA approved Ethyol for this use.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Patients receiving full dose amifostine should have antihypertensive therapy interrupted 24 hours before receiving amifostine
-Patients should be adequately hydrated prior to administration and kept in a supine position during administration.
-Monitor blood pressure at least every 5 minutes during the infusion. Care should be taken to monitor the blood pressure during and after the infusion for patients whose antihypertensive medication has been interrupted.
-Premedicate with antiemetics including dexamethasone and a serotonin 5HT3 receptor antagonist.
-Epinephrine and other appropriate measures should be available for treatment of serious allergic events such as anaphylaxis.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The reconstituted solution should be colorless. Discard if cloudiness or precipitates are observed.
Intravenous Administration
Reconstitution of IV infusions:
-During reconstitution, use gloves to avoid contact with the skin or mucous membranes.
-A vial may contain more drug than is required for the recommended dose, or multiple vials may be needed to obtain the recommended dose.
-Reconstitute each vial containing 500 mg amifostine with 9.7 mL of sterile 0.9% Sodium Chloride for Injection. The resultant solution should contain 50 mg/mL of amifostine and is chemically stable for up to 5 hours at room temperature (about 25 degrees C) or up to 24 hours under refrigeration (2 to 8 degrees C).
-Further dilute with 0.9% Sodium Chloride for injection in a polyvinylchloride (PVC) bag to a final concentration that ranges from 5 mg/mL to 40 mg/mL. The diluted product is chemically stable for up to 5 hours when stored at room temperature (approximately 25 degrees C) or up to 24 hours when stored under refrigeration (2 to 8 degrees C).
-The compatibility of amifostine with solutions other than 0.9% Sodium Chloride for Injection, or Sodium Chloride solutions with other additives, has not been examined. The use of other solutions is not recommended.
Intravenous (IV) infusion:
-For chemotherapy: Administer 30 minutes prior to chemotherapy by a 15 minute IV infusion. The 15-minute infusion is better tolerated than longer infusions.
-For radiation therapy: Administer 15 to 30 minutes prior to radiation therapy by a 3 minute IV infusion.
-Monitor blood pressure at least every 5 minutes during the infusion. Care should be taken to monitor the blood pressure during and after the infusion for patients whose antihypertensive medication has been interrupted.
Nausea and vomiting (grades 1 and 2, 66%; grade 3 or higher, 30%) were reported commonly when amifostine 910 mg/m2 IV was administered in 122 ovarian cancer patients who were receiving chemotherapy with cyclophosphamide and cisplatin in a randomized study. In this study, severe nausea and vomiting were experienced on day 1 in 19% of women who received amifostine prior to chemotherapy. Similarly, during the head and neck cancer study, 45% of the 150 patients who received amifostine 200 mg/m2 IV experienced mild nausea and vomiting (grades 1 and 2), while 8% of amifostine recipients developed severe nausea and vomiting (grade 3 or higher). Administer antiemetic medications (e.g., dexamethasone 20 mg IV and a serotonin 5-HT3 receptor antagonist) prior to and in conjunction with amifostine therapy. Ensure fluid balance is maintained if patients are receiving highly emetogenic chemotherapy.
Hypotension (grade 1 and 2, 54%; grade 3 or higher, 8%) was reported commonly when amifostine 910 mg/m2 IV was administered in 122 ovarian cancer patients who were receiving chemotherapy with cyclophosphamide and cisplatin in a randomized study. In the head and neck cancer study, 12% of the patients (n = 18/150) receiving amifostine 200 mg/m2 IV developed mild or moderate hypotension (grade 1 and 2), while 3% (n = 4/150) experienced drops in blood pressure of more than 20 mm Hg (grade 3 or higher hypotension). Hypotension is usually brief (mean onset: 14 minutes; mean duration 6 minutes) and has been accompanied with1 or more of the following symptoms: apnea, dyspnea, hypoxia, sinus tachycardia, bradycardia, extrasystoles, chest pain (unspecified), myocardial ischemia (angina), and seizures. Additionally, renal failure (unspecified), myocardial infarction, syncope, cardiac arrest, and respiratory arrest have been observed rarely during or after hypotensive episodes. Use of amifostine in patients with pre-existing dehydration or hypotension is not recommended. Antihypertensive therapy should be withheld for 24 hours prior to amifostine administration; do not give amifostine to patients who cannot have antihypertensive therapy held. Monitor blood pressure at least every 5 minutes during the amifostine infusion and thereafter as indicated. If hypotension occurs, place the patient in the Trendelenburg position and infuse normal saline through a separate IV line. Restart the amifostine infusion if blood pressure returns to normal within 5 minutes and the patient is asymptomatic. If the full dose cannot be given, subsequent amifostine doses should be reduced.
Decrease in serum calcium concentrations is a known effect with amifostine, and was observed in 1% of the 150 patients receiving amifostine 200 mg/m2 IV during the head and neck cancer study; however, significant hypocalcemia was not reported when amifostine 910 mg/m2 IV was administered in 122 ovarian cancer patients who were receiving 6 cycles of chemotherapy with cyclophosphamide and cisplatin in a randomized study. Monitor serum calcium levels in patients at risk for hypocalcemia (e.g., nephrotic syndrome, multiple amifostine infusions). Calcium supplements may be required in some patients.
Allergic reactions have been reported with amifostine use in clinical trials and in postmarketing surveillance, including rare cases of anaphylactoid reactions and cardiac arrest. Allergic reactions have been characterized by one or more of the following conditions: hypotension, fever, chills or rigors, dyspnea, hypoxia, chest pressure syndrome (chest tightness), cutaneous eruptions, pruritus, urticaria, and laryngeal edema. Promptly and permanently discontinue amifostine if a severe acute allergic reaction occurs; epinephrine and other appropriate supportive therapies to treat allergic reactions should be available when amifostine is administered.
Cutaneous eruptions have been reported commonly with amifostine use in clinical trials; most eruptions were not serious. However, serious skin reactions have occurred with amifostine use, including erythema multiforme and rarely Stevens-Johnson syndrome, toxicoderma, exfoliative dermatitis, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS). Some cases were fatal or required hospitalization. Serious reactions were seen more frequently when amifostine was used as a radioprotective agent. In addition, an injection site reaction, including rash (unspecified), erythema, pruritus, urticaria, pain, inflammation, bruising, and local swelling, has been reported during administration of amifostine. A cutaneous evaluation should be performed prior to, during, and after each amifostine infusion. Some serious skin reactions developed weeks after starting amifostine therapy. Permanently discontinue amifostine in patients who develop a serious or severe cutaneous reaction or skin reactions accompanied by fever or other body symptoms. Hold amifostine therapy, consult a dermatologic specialist, and consider obtaining a skin biopsy in patients who have any rash involving the lips or mucosa not caused by another etiology or erythematous, edematous, or bullous lesions on the palms of the hands or soles of the feet. Therapy may be restarted at the discretion of the treating physician.
Arrhythmias such as atrial fibrillation, atrial flutter, and supraventricular tachycardia (SVT) have been reported rarely with amifostine use in clinical trials and postmarketing surveillance. These arrhythmias were sometimes associated with hypotension or allergic reactions.
Transient hypertension and exacerbations of preexisting hypertension have been reported rarely with amifostine use in clinical trials and postmarketing surveillance.
Malaise has been reported during or following amifostine administration.
Flushing or a feeling of warmth has been reported during or following amifostine administration.
Diplopia, blurred vision, dizziness, and drowsiness (somnolence) have been reported during or following amifostine administration.
Hiccups and diarrhea have been reported during or following amifostine administration.
Sneezing has been reported during or following amifostine administration.
Amifostine is indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin chemotherapy in patients with advanced ovarian cancer. For the approved indication, clinical data do not suggest that the efficacy of cisplatin is altered by amifostine; however, data are limited concerning the effects of amifostine on the efficacy of chemotherapy used in other situations. Avoid use of amifostine in settings where chemotherapy can produce a significant survival benefit or cure, except in the context of a clinical trial.
Amifostine is indicated to reduce the incidence of xerostomia in patients undergoing post-operative radiation therapy for head and neck cancer. For the approved indication, clinical data do not suggest that the efficacy of radiation therapy is altered by amifostine. There are only limited data on the effects of amifostine on the efficacy of radiation therapy in other settings. Avoid use of amifostine in patients receiving definitive (e.g., curative) radiation therapy, except in the context of a clinical study, since there are insufficient data to exclude a tumor-protective effect in these patients. The effects of amifostine on the incidence of xerostomia and treatment-induced toxicity associated with combined chemotherapy and radiation or with accelerated and hyperfractionated radiation therapy have not been extensively studied. In addition, use of the drug in combination with radiation therapy may increase the risk for serious, sometimes fatal, cutaneous reactions. The reported incidence of serious rash (i.e., erythema multiforme, toxicoderma, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms) is higher in patients receiving amifostine as a radioprotectant than in patients receiving the drug as a chemoprotectant. Cutaneous reactions may develop weeks after drug initiation. Monitor patients closely before, during, and after amifostine therapy. Discontinue therapy if cutaneous reactions or mucosal lesions appear outside of the injection site or radiation port, or if erythematous, edematous, or bullous lesions appear on the palms and soles.
Amifostine should not be given to patients who have hypotension or in whom dehydration is present. Amifostine-induced hypotension is known to occur during intravenous infusion and is quickly reversible. Patients should not take antihypertensive medication 24 hours prior to receiving amifostine. Hypotension has also been associated with severe allergic reactions to amifostine. Patients should be adequately hydrated prior to administering amifostine and kept in a supine position during administration. Infusions should be no longer than 15 minutes to decrease the incidence of hypotension and other side effects. Monitor blood pressure every 5 minutes during amifostine infusion. If hypotension occurs, the patient should be placed in the Trendelenburg position and be given IV fluids using a separate IV line; see Dosage for guidelines for interrupting the amifostine infusion. If the blood pressure returns to normal within 5 minutes and the patient is asymptomatic, the infusion may be restarted so that the full amifostine dose can be administered. Care should be taken to monitor the blood pressure during and after the infusion of amifostine for patients whose antihypertensive medication has been interrupted since hypertension may be exacerbated by the discontinuation of antihypertensive medication and administration of IV fluids.
Amifostine is contraindicated in patients with known aminothiol hypersensitivity. Amifostine should not be used in these patients. In case of severe acute allergic reactions, amifostine should be immediately and permanently discontinued. Epinephrine and other appropriate measures should be available for treatment of serious allergic events such as anaphylaxis. Amifostine should be permanently discontinued for serious or severe cutaneous reactions or for cutaneous reactions associated with fever or other constitutional symptoms not known to be due to another etiology. Amifostine should be withheld and dermatologic consultation and biopsy considered for cutaneous reactions or mucosal lesions of unknown etiology appearing outside of the injection site or radiation port and for erythematous, edematous, or bullous lesions on the palms of the hand or soles of the feet (e.g., exfoliative dermatitis). Further treatment with amifostine should be at the physician's discretion based on medical judgment and appropriate dermatologic evaluation.
Amifostine should be used cautiously in patients with hypocalcemia. Serum calcium levels should be monitored during treatment with amifostine. Patients at risk for hypocalcemia include patients with renal disease, nephrotic syndrome, or patients receiving multiple doses of amifostine. These patients should be monitored closely. Amifostine-associated hypocalcemia is believed to occur as a result of parathyroid hormone inhibition. Calcium supplements may be needed in some patients.
The safety of amifostine in neonates, infants, children, geriatric patients, or those with pre-existing cardiac disease or cerebrovascular disease has not been established. Amifostine should also be used with caution in patients with conditions such as ischemic cardiac disease (e.g., angina or history of myocardial infarction), cardiac arrhythmias, congestive heart failure, or history of stroke or transient ischemic attacks. Amifostine should be used with caution in any patient in whom the common side effects of hypotension or nausea and vomiting may be more likely to have serious consequences.
No adequate and well-controlled human studies have been conducted to determine if use of amifostine is safe and effective during pregnancy; it is unknown if the drug causes fetal harm or affects reproductive capacity. In rabbits, amifostine was embryotoxic at 60% of the recommended human dose based on body surface area. Use during pregnancy is recommended only if the benefit to the mother justifies the potential risk to the fetus.
Data are limited regarding use of amifostine during breast-feeding, and its excretion into breast milk is unknown. The manufacturer recommends discontinuing breast feeding if treatment with the drug is required. However, because it is administered when breast-feeding is unlikely (immediately prior to chemotherapy or radiation) and because of its short half-life, the risk to a nursing infant is low. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
Based on data from animal reproduction studies, amifostine may cause fetal harm when administered to pregnant women; thus, women of childbearing potential should undergo pregnancy testing before receiving amifostine therapy.
For nephrotoxicity prophylaxis in patients receiving cisplatin for advanced ovarian cancer:
NOTE: Amifostine has been designated an orphan drug by the FDA for this indication.
NOTE: Amifostine may interfere with the antitumor activity of chemotherapy regimens. DO NOT use in patients receiving chemotherapy for other malignancies in which chemotherapy can produce a significant benefit or cure, except in the context of a clinical study.
Intravenous dosage:
Adults: 910 mg/m2 IV over 15 minutes starting 30 minutes prior to chemotherapy. Chemotherapy should be started 15 minutes after completion of amifostine infusion. Monitor blood pressure frequently; the infusion should be interrupted if the systolic blood pressure (SBP) decreases significantly. If the full dose of amifostine (i.e., 910 mg/m2) cannot be administered prior to cisplatin therapy, reduce the amifostine dose to 740 mg/m2 for subsequent cycles.
For xerostomia prophylaxis in patients undergoing post-operative radiation treatment of head and neck cancer, where the radiation port includes a substantial portion of the parotid glands:
NOTE: Amifostine has been designated an orphan drug by the FDA for this indication.
NOTE: Amifostine may interfere with the antitumor activity of radiotherapy regimens. DO NOT use in patients receiving definitive radiotherapy, except in the context of a clinical study.
Intravenous dosage:
Adults: 200 mg/m2 IV once daily as a 3-minute infusion starting 15 to 30 minutes prior to standard fraction radiation therapy (1.8 to 2 Gy). Adequately hydrate the patient prior to amifostine administration. Monitor blood pressure before and immediately after the infusion and more frequently if indicated. In a phase III trial, after about 1 month of treatment, 78% of head and neck cancer patients receiving radiation therapy alone, compared with 51% of patients treated with amifostine prior to radiation, experienced moderate-to-severe xerostomia. At 1 year following the completion of radiation therapy, 72% of amifostine-treated patients could produce a clinically relevant volume of saliva (more than 0.1 mL), compared to only 49% of those who did not receive amifostine.
For bone marrow suppression prophylaxis*, nephrotoxicity prophylaxis*, or neurotoxicity prophylaxis* in patients receiving antineoplastic agents and/or fractionated radiation therapy:
Intravenous dosage:
Adults: In most studies, amifostine 100 to 340 mg/m2/day IV over 15 minutes prior to each dose of chemotherapy or radiation therapy was given. In one study, the maximum tolerated dose of amifostine in patients prior to daily irradiation of 170 to 200 cGy was 340 mg/m2/day IV for 4 days every week. Patients receiving hemibody irradiation of 600 to 700 cGy have received amifostine at doses of 600 to 900 mg/m2 IV 15 to 30 minutes prior to radiation therapy. Monitor blood pressure frequently; the infusion should be interrupted if the systolic blood pressure (SBP) decreases significantly according to the adjustment guidelines.
For the promotion of hematopoiesis in patients with myelodysplastic syndrome (MDS)*, including refractory anemia (RA)*, refractory anemia with ringed-sideroblasts (RARS)* and refractory anemia with excess blasts (RAEB)*:
NOTE: Amifostine has been designated an orphan drug by the FDA for this indication.
Intravenous dosage:
Adults: Patients were initially treated with 100 mg/m2 IV 3-times weekly, increasing the dosage by 100 mg/m2 IV 3 times weekly up to 300 mg/m2 IV 3 times weekly. Initial treatment was for 8 weeks, and if patients responded or had stable disease, treatment continued for 6 months. Of the patients treated, 40% had a greater than 50% increase in platelets and absolute neutrophil counts (written communication, 2/99).
Therapeutic Drug Monitoring:
The infusion should be interrupted if the systolic blood pressure (SBP) decreases significantly. The infusion may be restarted if the SBP returns to normal within 5 minutes and the patient is asymptomatic.
If baseline SBP is less than 100: Stop amifostine infusion if SBP decreases by 20 mmHg.
If baseline SBP is 100 to 119: Stop amifostine infusion if SBP decreases by 25 mmHg.
If baseline SBP is 120 to 139: Stop amifostine infusion if SBP decreases by 30 mmHg.
If baseline SBP is 140 to 179: Stop amifostine infusion if SBP decreases by 40 mmHg.
If baseline SBP is 180 or more: Stop amifostine infusion if SBP decreases by 50 mmHg.
Maximum Dosage Limits:
-Adults
910 mg/m2 IV.
-Geriatric
910 mg/m2 IV.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustments are recommended.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available.
*non-FDA-approved indication
Acebutolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Aliskiren; Hydrochlorothiazide, HCTZ: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Alpha-blockers: (Major) Patients receiving alpha-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Amiloride: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Amiloride; Hydrochlorothiazide, HCTZ: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Amlodipine: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Amlodipine; Atorvastatin: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Amlodipine; Benazepril: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Amlodipine; Celecoxib: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Amlodipine; Olmesartan: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Amlodipine; Valsartan: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses. (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Angiotensin II receptor antagonists: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Angiotensin-converting enzyme inhibitors: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Atenolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Atenolol; Chlorthalidone: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses. (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Azilsartan: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Azilsartan; Chlorthalidone: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Benazepril: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Benazepril; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Beta-blockers: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Betaxolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Bisoprolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses. (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Brimonidine; Timolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Calcium-channel blockers: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Candesartan: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Candesartan; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Captopril: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Captopril; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Carteolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Carvedilol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Central-acting adrenergic agents: (Major) Patients receiving central-acting adrenergic agents should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Chlorothiazide: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Chlorthalidone: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Clevidipine: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Clonidine: (Major) Patients receiving central-acting adrenergic agents should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Diazoxide: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Diltiazem: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Dorzolamide; Timolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Doxazosin: (Major) Patients receiving alpha-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Enalapril, Enalaprilat: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Enalapril; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Eplerenone: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Epoprostenol: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Eprosartan: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Eprosartan; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Esmolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Felodipine: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Fenoldopam: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Fosinopril: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Fosinopril; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Guanfacine: (Major) Patients receiving central-acting adrenergic agents should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Hydralazine: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Hydralazine; Isosorbide Dinitrate, ISDN: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Hydrochlorothiazide, HCTZ: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Hydrochlorothiazide, HCTZ; Moexipril: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Iloprost: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Irbesartan: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Irbesartan; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Isradipine: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Labetalol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Levamlodipine: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Levobunolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Lisinopril: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Lisinopril; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Losartan: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Losartan; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Mecamylamine: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Methyldopa: (Major) Patients receiving central-acting adrenergic agents should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Metolazone: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Metoprolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Metoprolol; Hydrochlorothiazide, HCTZ: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses. (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Minoxidil: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Moexipril: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Nadolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Nebivolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Nebivolol; Valsartan: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Nicardipine: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
NIFEdipine: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Nimodipine: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Nisoldipine: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Nitroprusside: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Olmesartan: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses. (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Olmesartan; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Perindopril: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Perindopril; Amlodipine: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Phenoxybenzamine: (Major) Patients receiving alpha-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Phentolamine: (Major) Patients receiving alpha-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Pindolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Potassium-sparing diuretics: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Prazosin: (Major) Patients receiving alpha-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Propranolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Quinapril: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Quinapril; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Ramipril: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Sacubitril; Valsartan: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Sotalol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Spironolactone: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Telmisartan: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Telmisartan; Amlodipine: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Telmisartan; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Terazosin: (Major) Patients receiving alpha-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Thiazide diuretics: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Timolol: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Trandolapril: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Trandolapril; Verapamil: (Major) Patients receiving angiotensin-converting enzyme inhibitors should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Treprostinil: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Triamterene: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Triamterene; Hydrochlorothiazide, HCTZ: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Valsartan: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Valsartan; Hydrochlorothiazide, HCTZ: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Vasodilators: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
Verapamil: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Clinically, amifostine administered prior to cytotoxic therapy attenuates the hematologic, neurologic, and/or nephrotoxic effects secondary to chemotherapy or radiation. Amifostine can increase tolerable doses of alkylating agents, other DNA-reactive agents and ionizing radiation. The cytoprotective activity of amifostine is due to the dephosphorylated active thiol, WR-1065. Amifostine is activated by membrane-bound alkaline phosphatase enzymes and is absorbed in a pH-dependent manner. WR-1065 inactivates charged carbonium ions of activated alkylating agents by directly binding to the reactive molecule, thereby protecting nucleic acids from alkylation. The increased expression and activity of alkaline phosphatase in normal cells as opposed to tumor cells is one reason for the selective protection of amifostine. In addition, the lower pH surrounding tumor cells lessens alkaline phosphatase activity. WR-1065 also acts as a hydrogen donor to repair damaged DNA and is a free radical scavenger of reactive oxygen species created following exposure to antineoplastic agents and radiation. This activity supplements the protection provided by other intrinsic free-radical scavengers such as glutathione. The renal protective effects of amifostine are due to the presence of sulfhydryl groups. As cisplatin binds extensively to renal tubule proteins, the additional sulfhydryl groups provided by amifostine provide protection to the renal tubules. In comparison with colony-stimulating factors, amifostine provides trilineage protection (red blood cells, platelets, and white blood cells) to hematopoietic stem cells, whereas colony-stimulating factors stimulate recovery of single cell lines (e.g., granulocytes).
Amifostine is administered intravenously. Following administration, amifostine is rapidly taken up by normal cells and is dephosphorylated to WR-1065 and other metabolites. Amifostine metabolism via alkaline phosphatase enzymes may be saturable resulting in increased drug exposure at higher doses leading to more adverse reactions. Lower doses of amifostine (i.e., 740 mg/m2) result in similar efficacy and better tolerance with a decreased incidence of hypotension and nausea/vomiting. Animal data reveal extensive tissue distribution, especially to the liver, kidney, heart, bone marrow, and salivary glands. Amifostine does not cross the blood-brain barrier. Steady-state levels occur within 10 to 15 minutes. The beta half-life of amifostine is less than 10 minutes.
-Route-Specific Pharmacokinetics
Intravenous Route
Following administration, amifostine is rapidly taken up by normal cells and is dephosphorylated to WR-1065 and other metabolites. Measurable levels of the thiol metabolite have been found in bone marrow cells 5 to 8 minutes after intravenous infusion. Amifostine and its metabolites produce concentrations in normal tissues that can reach as much as 100-fold greater than in tumor tissues in the first 30 minutes after administration. A 10-fold difference may be maintained for at least 60 minutes.