Deferoxamine

560.68

560.68

200-738-5

J06Y7MXW4D

527604

DTXSID7022887

C416

V03AC01|V - Various

2924199090

206

-2.2

Solid

1.212g/cm3

140 °C

627.9°C (rough estimate)

1.537

9.90e-02 g/L

LD50 oral in mouse: 1340mg/kg

CRYSTALS FROM DIL ALC /MONOHYDRATE/|CRYSTALS FROM SLIGHTLY ACIDIC METHANOL /HYDROCHLORIDE/|CRYSTALS FROM DIL ALC /METHANESULFONATE/|CRYSTALS FROM N-PROPANOL /N-ACETYL DERIV/

RECONSTITUTED SOLN ARE STABLE FOR 2 WK @ ROOM TEMP /MESYLATE/

P264, P270, P301+P312, P330, P501

H302

|Warning|H302 (98.98%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 197 companies from 3 notifications to the ECHA C&L Inventory.

Intravenous LD50 in mouse, rat, and rabbit is 340 mg/kg, 520 mg/kg, and 600 mg/kg, respectively. Subcutaneous LD50 in mouse and rat is 1600 mg/kg and >1000 mg/kg, respectively. Oral LD50 in mouse and rat is >3000 mg/kg and >1000 mg/kg, respectively. Nephrotoxicity, ototoxicity and retinal toxicity have been reported following long-term administration for chronic iron overload.

In large clinical trials, elevations in serum aminotransferase levels were rare in patients receiving deferoxamine and instances of acute, clinically apparent liver injury were not reported. Patients with transfusion related iron overload often have concurrent chronic hepatitis B or C, and elevations of serum aminotransferase levels during chelation therapy may be due to natural fluctuations in the underlying chronic liver disease activity. Nevertheless, elevations in serum aminotransferase levels and “hepatic dysfunction” are listed as potential adverse events in product labels for deferoxamine. After an early report of hepatitis occurring in patient on hemodialysis receiving deferoxamine to reduce aluminum levels, there have been no further published instances of clinically apparent liver injury that have been convincingly linked to deferoxamine therapy.

THE CONCOMITANT ORAL ADMINISTRATION OF ASCORBIC ACID (0.5 TO 1 G TWICE DAILY) SEEMS TO IMPROVE THE CHELATING ACTION OF DEFEROXAMINE IN HEMOCHROMATOSIS, PARTICULARLY IF THERE IS A VITAMIN C DEFICIENCY.

Less than 10% bound to serum proteins in vitro.

Used to treat acute iron or aluminum toxicity (an excess of aluminum in the body) in certain patients. Also used in certain patients with anemia who must receive many blood transfusions.

Deferoxamine is a parenterally administered iron chelating agent used to treat transfusion related chronic iron overload. Deferoxamine rarely causes serum aminotransferase elevations during therapy and has not been convincingly linked to instances of clinically apparent liver injury.

Hematological Agents

Antidotes; Chelating Agents|/DEFEROXAMINE IS/ A CHELATING AGENT THAT IS SPECIFIC FOR IRON. IT IS USED FOR THE TREATMENT OF SEVERE IRON INTOXICATION, IRON OVERLOAD RESULTING FROM HEMOLYSIS (FROM DRUGS, THALASSEMIA, SICKLE-CELL ANEMIA, FREQUENT BLOOD TRANSFUSIONS, ETC) OR IRON STORAGE DISEASE. ... ALTHOUGH IT DOES NOT APPRECIABLY BIND FERROUS IRON, IT HAS NEVERTHELESS PROVEN USEFUL IN THE TREATMENT OF INTOXICATION BY FERROUS AS WELL AS BY FERRIC SALTS...|ALTHOUGH RESULTS...IN PRIMARY HEMOCHROMATOSIS & HEMOSIDEROSIS SECONDARY TO HEPATIC CIRRHOSIS ARE DISAPPOINTING, SOME PATIENTS WITH TRANSFUSION SIDEROSIS RESPOND WELL TO DEFEROXAMINE THERAPY.|...HAS BEEN USED CLINICALLY BOTH SYSTEMICALLY & LOCALLY IN EYE FOR OCULAR SIDEROSIS & FOR IRON FOREIGN BODIES IN EYE.|For more Therapeutic Uses (Complete) data for DESFERRIOXAMINE (14 total), please visit the HSDB record page.

/DESPITE EFFECTIVENESS OF DEFEROXAMINE AS IRON CHELATING AGENT/...OTHER MEASURES SUCH AS INDUCED VOMITING, AIRWAY MAINTENANCE, GASTRIC LAVAGE WITH SODIUM PHOSPHATE OR SODIUM BICARBONATE TO FORM NONABSORBABLE IRON SALTS, AND CONTROL OF METABOLIC ACIDOSIS AND SHOCK, ARE ALSO IMPORTANT.|BECAUSE OF SIDE EFFECTS, DEFEROXAMINE SHOULD NOT BE USED TO TREAT MILD IRON INTOXICATION. /MESYLATE/|THERE ARE NO ABSOLUTE CONTRAINDICATIONS TO THE USE OF DEFEROXAMINE WHEN TREATING ACUTE IRON INTOXICATION OR HEMOCHROMATOSIS. SINCE THE DRUG AND THE FERRIOXAMINE COMPLEX ARE EXCRETED PRIMARILY BY THE KIDNEYS, DEFEROXAMINE IS CONTRAINDICATED IN PATIENTS WITH SEVERE RENAL DISEASE OR ANURIA.|ALTHOUGH CHRONIC RENAL INFECTION MAY BE EXACERBATED IN SOME PATIENTS, RENAL DAMAGE IN OTHERWISE-NORMAL INDIVIDUALS HAS NOT BEEN DEMONSTRATED EVEN AFTER 2 YR OF DEFEROXAMINE THERAPY.

Deferoxamine, otherwise known as desferrioxamine or desferal, is a chelating agent used to remove excess iron or aluminum from the body. It acts by binding free iron or aluminum in the bloodstream and enhancing its elimination in the urine. By removing excess iron or aluminum, the agent reduces the damage done to various organs and tissues, such as the liver.

Low-molecular-weight compounds produced by microorganisms that aid in the transport and sequestration of ferric iron. (The Encyclopedia of Molecular Biology, 1994) (See all compounds classified as Siderophores.)

Deferoxamine is rapidly absorbed after intramuscular or subcutaneous administration, but only poorly absorbed from the gastrointestinal tract in the presence of intact mucosa.|Deferoxamine mesylate is metabolized principally by plasma enzymes, but the pathways have not yet been defined. Some is also excreted in the feces via the bile.|THE DRUG IS...READILY EXCRETED IN URINE.

Deferoxamine is mainly metabolised in the plasma and hepatic metabolism is minimal. A number of metabolites have been isolated but not characterised. Some metabolites of deferoxamine, most notably the product of oxidative deamination, also chelate iron, and thus the antidotal effect of the drug appears unaffected by hepatic metabolism.|DEFEROXAMINE IS METABOLIZED PRINCIPALLY BY PLASMA ENZYMES, ALTHOUGH THE PATHWAYS HAVE NOT YET BEEN DEFINED.

Biphasic elimination pattern in healthy volunteers with a first rapid phase half life of 1 hour and a second slow phase half-life of 6 hours.

Deferoxamine works in treating iron toxicity by binding trivalent (ferric) iron (for which it has a strong affinity), forming ferrioxamine, a stable complex which is eliminated via the kidneys. 100 mg of deferoxamine is capable of binding approximately 8.5 mg of trivalent (ferric) iron. Deferoxamine works in treating aluminum toxicity by binding to tissue-bound aluminum to form aluminoxamine, a stable, water-soluble complex. The formation of aluminoxamine increases blood concentrations of aluminum, resulting in an increased concentration gradient between the blood and dialysate, boosting the removal of aluminum during dialysis. 100 mg of deferoxamine is capable of binding approximately 4.1 mg of aluminum.|DEFEROXAMINE HAS...REMARKABLY HIGH AFFINITY FOR FERRIC IRON... IT...COMPETES FOR IRON OF FERRITIN & HEMOSIDERIN, BUT IT REMOVES ONLY SMALL AMOUNT OF IRON OF TRANSFERRIN. ... GIVEN ORALLY, DEFEROXAMINE BINDS IRON IN LUMEN OF BOWEL & RENDERS THE METAL NONABSORBABLE.|IT READILY COMPLEXES WITH FERRIC ION TO FORM FERRIOXAMINE, COLORED, STABLE, WATER-SOL CHELATE; IT ALSO HAS LIMITED AFFINITY FOR FERROUS ION. /MESYLATE/

PAIN & INDURATION MAY OCCUR @ SITE OF IM INJECTION. OTHER UNTOWARD EFFECTS INCL ERYTHEMA, FLUSHING, DIARRHEA, BLURRING OF VISION, ABDOMINAL DISCOMFORT, MUSCULAR SPASMS IN LEGS, ITCHING, TACHYCARDIA, & FEVER. IN LONG TERM THERAPY, VARIOUS ALLERGIC REACTIONS, INCL ANAPHYLAXIS, HAVE BEEN REPORTED. /MESYLATE/|REACTIONS HAVE INCLUDED HYPOTENSION, PROBABLY DUE TO HISTAMINE RELEASE (ESP DURING IV ADMIN), SKIN RASHES, & GI IRRITATION. OCCASIONAL CASES OF CATARACT FORMATION IN MAN HAVE BEEN REPORTED...|A WOMAN WITH BETA-THALASSAEMIA INTERMEDIA, AND IRON OVERLOAD FOLLOWING MANY YEAR'S THE COURSE OF THIS TREATMENT SHE DEVELOPED TINNITUS, WHICH WAS CONSIDERED TO BE A RARE COMPLICATION OF THE USE OF THIS CHELATING AGENT.|DESFERRIOXAMINE WAS GIVEN INTRAVENOUSLY, AT HIGHER DOSES THAN PREVIOUSLY REPORTED, TO COUNTER THE EFFECTS OF TRANSFUSION-INDUCED IRON OVERLOAD IN FOUR PATIENTS WITH BETA THALASSAEMIA MAJOR. IN TWO OF THEM RETINAL ABNORMALITIES DEVELOPED, PRESENTING WITH NIGHT BLINDNESS AND FIELD DEFECTS, WHICH IMPROVED ON WITHDRAWAL OF THE DRUG.

Deferoxamine

STERILE DEFEROXAMINE MESYLATE, USP (DESFERAL MESYLATE), IS AVAILABLE IN AMPULES CONTAINING 500 MG OF THE DRUG. /MESYLATE/|DESFERAL (CIBA). INJECTION: LYOPHILIZED POWDER (FOR SOLN) 500 MG.

THE IRON-CHELATING AGENT DESFERROXAMINE INHIBITED BOTH THE BASELINE AND IRON-STIMULATED AUTOXIDATION OF DOPAMINE OR NOREPINEPHRINE. DESFERROXAMINE APPEARS TO BE A USEFUL TOOL THAT MAY BE ADDED TO SOLUTIONS CONTAINING CATECHOLAMINES TO PREVENT THEIR DEGRADATION.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Fatty Acyls [FA] -> Fatty amides [FA08] -> N-acyl amines [FA0802]