Amifostine [Discontinued in SA Market]

Registered South African indications:

• Reduce the neutropenia related risk of infection
• Reduce the cumulative renal toxicity in patients with ovarian cancer
• Reduce xerostomia

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Risk factors for hypocalcemia
• Cardiovascular disease or whom the adverse effects of hypotension may have serious adverse events
• Cerebrovascular disease

Forms avail. in SA and covered in this monograph: inj

Used for the treatment of

Reduce the neutropenia related risk of infection
- Due to the combination regimen cyclophosphamide and cisplatin
Reduce the cumulative renal toxicity
- Associated with repeated administration of cisplatin in patients with advanced ovarian cancer
Reduce the incidence of moderate to severe xerostomia
- In patients undergoing post undergoing post-operative radiation treatment for head and neck cancer

Consult specialist for dosages and regimens

Not established for use in children

Pregnancy

• FDA Pregnancy Category C

Breastfeeding

• Caution; not recommended

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• No dose adjustment recommended

Elderly

• No dose adjustment recommended

Central Nervous System Disorders

• Chills
• Dizziness
• Drowsiness
• Malaise
• Sensation of cold

Cardiovascular Disorders

• Hypotension
• Bradycardia
• Chest pain
• Extrasystoles
• Flushing
• Ischemic heart disease
• Tachycardia

Respiratory Disorders

• Hiccups
• Apnea
• Dyspnea
• Hypoxia
• Sneezing

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhea

Endocrine and Metabolic Disorders

• Hypocalcemia 

Skin and Subcutaneous Tissue Disorders

• Erythema multiforme
• Skin rash

Immune, Blood and Lymphatic System Disorders

• Anaphylaxis
• Fever
• Injection site reaction 

Sensory Disorders

• Blurred vision
• Diplopia

• Blood pressure lowering agents
• Obinutuzumab

• Blood pressure

Specific cases may require

• Calcium levels

Amifostine is a pro-drug that is dephosphorylated to the active metabolite WR-1065 (free thiol), by alkaline phosphatase. This active metabolite is believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. The ability of amifostine to differentially protect normal tissues is attributed to the higher capillary alkaline phosphatase activity, higher pH and better vascularity of normal tissue relative to tumour tissue, which results in a more rapid generation of the active third metabolite as well as a higher rate constant for uptake into cells. The higher concentration of the thiol metabolite in normal tissues is available to bind to, and thereby detoxify, reactive metabolites of cisplatin. This thiol metabolite can also scavenge reactive oxygen species generated by exposure to either cisplatin or radiation.

Injection (per vial) 500mg

• Ethyol (Schering Plough) originator