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Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals

-2.2

-1.52

Breast Feeding; Lactation; Chelating Agents; Iron Chelating Agents

Antidotes and other substances used in poisonings > Specific

MP: 138-140 °C /MONOHYDRATE/; 172-175 °C /HYDROCHLORIDE/; 148-149 °C /METHANESULFONATE/

MP: 180-182 °C /N-ACETYL DERIV/

138 - 140 °C

CRYSTALS FROM DIL ALC /MONOHYDRATE/

CRYSTALS FROM SLIGHTLY ACIDIC METHANOL /HYDROCHLORIDE/

CRYSTALS FROM DIL ALC /METHANESULFONATE/

CRYSTALS FROM N-PROPANOL /N-ACETYL DERIV/

Warning

H302 (97.1%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 69 reports by companies from 3 notifications to the ECHA C&L Inventory.

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.

Chronic deferoxamine therapy can lead to sensorineural hearing loss and retinopathy. Though the mechanism of ocular injury is not well understood, it appears to partially occur due to damage to the retinal pigment epithelium, which can lead to decreased visual acuity, visual field defects, and color vision defects. Hearing and vision loss can be reversible if the patient discontinues the drug early in the course. Growth retardation can also occur in children receiving deferoxamine treatment, and clinicians should monitor patients for appropriate growth velocity over time.

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.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

deferoxamine

Desferal®

Chelating agents

Not Applicable

no-DILI-concern

DOGS TOLERATE SINGLE IV DOSES UP TO 100 MG/KG WITH SIGNS SUGGESTING TRANSIENT HYPOTENSION.

...IT HAS PRODUCED OPACITIES IN CRYSTALLINE LENS IN DOGS, CATS, & RATS WHEN GIVEN BY DAILY SC INJECTION FOR LONG PERIODS @ DOSAGES SO LARGE THAT THEY PRODUCE SEVERE GASTROENTERITIS.

INJECTION OF 28.5% SOLN SUBCONJUNCTIVALLY HAS CAUSED SLIGHT CHEMOSIS & HYPEREMIA. ... INJECTION OF 50 MG SUBCONJUNCTIVALLY WAS TOLERATED BY EYES OF MONKEYS...

...50 MG INJECTED SUBCONJUNCTIVALLY IN RABBITS EVERY 1-3 DAYS FOR SEVERAL MO WAS TOLERATED...BUT 200 MG SUBCONJUNCTIVALLY IN RABBITS CAUSED REDN IN RESPONSE OF PUPIL TO LIGHT, CONGESTION OF UVEA, & EXUDATIVE DETACHMENT OF CHOROID & RETINA...

INTRAVITREAL INJECTIONS OF 5 MG DEFEROXAMINE IN RABBITS PROVED VERY TOXIC, CAUSING WIDESPREAD HEMORRHAGIC NECROSIS, PARTICULARLY AFFECTING RODS & CONES OF RETINA & EXTINGUISHING ELECTRORETINOGRAM.

V03AC01

V - Various

QV - Various

V03AC01

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.

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/

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.

J06Y7MXW4D

DEFEROXAMINE

Mechanisms of Action [MoA] - Iron Chelating Activity

Established Pharmacologic Class [EPC] - Iron Chelator

Deferoxamine is an Iron Chelator. The mechanism of action of deferoxamine is as an Iron Chelating Activity.

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.

MEDICATION

Use (kg; approx.) in Germany (2009): >100

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.