Amifostine

As a cytoprotective adjuvant, Amifostine is used therapeutically to reduce fever and infection associated with neutropenia, which is induced by DNA-binding and platinum-containing agents.

Overview:

Amifostine was originally developed to reduce kidney toxicity from cisplatin in lung cancers, however it has also proven useful in reducing the incidences of xerostomia in patients who are undergoing radiotherapy for cancers in the neck and head. It is an organic thiophosphate medicine which is split in two with water and alkaline phosphatase to create a cytoprotective metabolite which protects non-cancerous tissues.

This medicine is typically administered intravenously (often diluted with saline in a drip) during long-form radiotherapy and chemotherapy treatments in order to alleviate some of the unpleasant side effects associated with these treatments.

Conditions treated:

  • Cancer

Type of medicine:

  • Cytoprotective adjuvant

Side effects:

Along with the required effects, Amifostine can also cause some unwanted side effects. Although not all of these side effects will occur, some may require additional medical attention in order to control them. Some of the most common side effects experienced by patients undergoing treatment with Amifostine include: confusion, blurred vision, dizziness and lightheadedness, feeling faint when getting up from a prone position, irregular or fast breathing, loss of consciousness, itching, vomiting, skin rash, swollen or peeling skin, swelling of the eyes or eyelid area, unusual tiredness, weakness, and excess sweating.

Some of these side effects are caused by the cancer the patient is being treated for, and others may appear as a result of radiotherapy or chemotherapy. Amifostine can actually be beneficial in combatting some of these effects, although it can take some time before the patient’s body adjusts. As the patient continues treatment with the drug, as administered by a healthcare professional, many (if not all) of these symptoms should lessen or subside either completely or to a bearable level.

Other side effects, which are experienced rarely, but enough to warrant mentioning, include: chills, joint and muscle pain, loss of bladder control, a feeling of coldness, muscle cramps in the extremities, low blood pressure, faint pulse, fever, irritated eyes, skin lesions with a purple center, seizures, ulcers or sores in the mouth and on the lips, tremors, sudden loss of consciousness, palpitations, headaches, hiccups, sneezing, pounding in the ears, redness or flushing of the face or neck, and loss of appetite.

While most of these symptoms will subside over the course of treatment, it is important for patients to notify their physician if side effects are particularly uncomfortable or unbearable. Healthcare professionals should be able to offer advice on how to alleviate minor symptoms, and may offer corrective actions or treatments in the event of severe side effects.

Cardiovascular side effects:

Approximately 62% of patients undergoing treatment with Amifostine will experience a transient reduction in blood pressure (hypotension), and arrhythmias (irregular heartbeats) such as supraventricular tachycardia and atrial fibrillation. In rare instances, this can cause short-term loss of consciousness, however in a clinical environment this should not put the patient under any undue risk.

Hypersensitivity:

In some patients, an acute allergic reaction to Amifostine has been reported. In such instances, treatment with this medication should be discontinued immediately and permanently. If the patient suffers a serious anaphylactic reaction, ephinephrine should be administered. Because of this risk, albeit a small one, access to an epi-pen or other anti-anaphylaxis measures should be on-hand in a clinical setting.

Dosage for cancer:

As with all medicines, it is important that Amifostine is only administered as directed by a qualified healthcare professional. This means patients should not be administered with larger doses than prescribed, or larger frequencies. A doctor should advise when it is suitable to stop taking Amifostine, which is typically towards the end or shortly after a course of radiotherapy or chemotherapy.

The typical adult dose of Amifostine to treat cumulative renal toxicity associated with continuous administration of cisplatin is 910mg/m2. The dose should be administered once a day as a 15-minute intravenous infusion, approximately 30 minutes before chemotherapy or radiotherapy begins. Extended infusions can be used if prescribed by a doctor, although these are not as well-tolerated by the body.

Prior to Amifostine infusion, patients should ensure that they are adequately hydrated and laid in a face-up position for the duration of the infusion. During infusion, blood pressure should be monitored at least every five minutes or as directed by a qualified healthcare professional. Patients who are dehydrated should not be permitted to commence with treatment.

Infusion with Amifostine should be interrupted if systolic blood pressure drops significantly from the baseline value, as per the following guidelines:

  • If baseline systolic blood pressure is less than 100mm Hg, and decreases by 20mm Hg during infusion
  • If baseline systolic blood pressure is between 100-119mm Hg, and decreases by 25mm Hg during infusion
  • If baseline systolic blood pressure is between 120-139mm Hg, and decreases by 30mm Hg during infusion
  • If baseline systolic blood pressure is between 140-179mm Hg, and decreases by 40mm Hg during infusion
  • If baseline systolic blood pressure is greater than 180mm Hg, and decreases by 50mm Hg during infusion

An interrupted infusion may be restarted if blood pressure returns to normal levels within five minutes and the patient is asymptomatic and showing no signs of discomfort. If the patient is not fit for the full dose of Amifostine to be administered, doses for subsequent cycles of chemotherapy should be adjusted to 740/mg2.

Antiemetic medication, such as dexamethasone, can be administered intravenously along with a serotonin 5-HT3 agonist in conjunction with Amifostine treatment.

Dosage for malignant disease:

To reduce moderate to severe xerostomia in patients who are undergoing post-operative treatment for cancers of the head and neck, the recommended dose of Amifostine is 200mg/m2, administered once a day as a 3-minute intravenous infusion, commencing 15 to 30 minutes before standard fractional radiation therapy.

Interactions:

All medicines have the potential to react with other drugs or chemicals in the body, and these interactions can cause the effects of the medication to change, or even produce potentially harmful side effects. For these reasons, it is imperative that patients keep a detailed list of all medicines they are currently taking, including the dosage and frequency of each drug. This applies to over the counter treatments, herbal supplements and vitamins as well as prescribed medicines.

Below is a list of medications known to have majorly interacted with Amifostine. If the patient is currently taking any of these drugs, he or she should inform their doctor before beginning treatment:

  • Etelcalcetide
  • Parsabiv

Use of Amifostine in conjunction with Etelcalcetide can decrease the levels of calcium in the blood, and the decision to use both of these medicines at once should be only taken by a doctor who understands the risks and has determined that this is the best possible course of treatment.

Other medications known to have minor interactions with Amifostine include:

  • Amlopidine
  • Atenolol
  • Avapro
  • Bepridil
  • Bumex
  • Bystolic
  • Chlorothiazide
  • Calan
  • Coreg
  • Demadex
  • Doxazosin
  • Esmolol
  • Felodipine
  • Guanabenz
  • Hydralazine
  • Isordil
  • Inspra
  • Levitra
  • Mannitol
  • Nitroglycerin
  • Olmesartan
  • Sildenafil
  • Sorine
  • Terazosin
  • Univasc
  • Zaroxylin
  • Zestril

Many of these medications can cause excessively low blood pressure when combined with Amifostine. Patients should allow their doctor to determine whether treatment with Amifostine is safe in conjunction with one or more of these drugs before commencing treatment.

Warnings:

Patients at risk of hypocalcemia, such as those receiving multiple Amifostine doses or those with nephrotic syndrome, should have serum calcium levels regularly monitored during treatment with the drug.

Amifostine may not be suitable for patients who are currently suffering from, or have recently suffered from:

  • Kidney disease
  • Heart disease
  • Stroke

Mothers are advised not to breastfeed when receiving treatment with Amifostine, as the medication could potentially by excreted in breastmilk. It is not known whether the compound poses a risk to infants, although FDA advice is to refrain from feeding infants when receiving treatment with a drug which has not been sufficiently studied in those under the age of 18.

Patients who are currently undergoing treatment for edema associated with congenital heart failure should avoid using Amifostine. This is because the diuretic effects of medicines used to treat swelling and water retention can cause the patient to become dehydrated, and combining this with Amifostine can result in a severe drop in blood pressure.

In some patients, serious cutaneous reactions have been reported, including (but not limited to) Stevens-Johnson syndrome, toxoderma, necrolysis and exfoliative dermatitis – most notably when Amifostine is used as a radioprotectant. In rare instances, these reactions can prove fatal. It is therefore vital that patients only receive treatment with Amifostine in a clinical environment, as overseen by a doctor and/or a team of healthcare professionals.

Storage:

Amifostine is shipped in vials, diluted solutions and reconstituted solutions. Intact vials should be stored at room temperature (20C to 25C). Solutions for intravenous infusion are stable for periods not exceeding 5 hours at room temperature, or 24 hours when kept refrigerated (between 2C and 5C).

Because Amifostine is generally only administered in a clinical environment, the storage and disposal of solutions and vials should be the responsibility of the patient’s healthcare provider, who will ensure that the medicine is destroyed in accordance with local and national laws pertaining to controlled substances and hazardous materials.

Summary:

Amifostine is effective in preventing and reducing side effects and symptoms associated with renal toxicity resulting from repeated doses of radiotherapy, chemotherapy and cisplatin in patients with advanced stages of lung, head and neck cancers.

Care should be taken when administering Amifostine, with regular monitoring of blood pressure and calcium levels commencing during and after infusion. Healthcare professionals should also take care to ensure that patients are hydrated prior to treatment with an IV solution.

In the US, Amifostine is often marketed under the brand name Ethyol. It is classed an an antidote and chemoprotective agent, and was approved by the FDA in 1995. It's used in oncology departments across the world.

Amifostine may also have some “off label” uses for other conditions besides the prevention of chemo-related side effects, although the manufacturer offers no recommendation and any such uses should be decided upon by a qualified healthcare practitioner.

Resources
Last Reviewed:
December 10, 2017
Last Updated:
December 22, 2017