Deferasirox

Trade Names:
Exjade
- Tablets for oral suspension 125 mg
- Tablets for oral suspension 250 mg
- Tablets for oral suspension 500 mg

Pharmacology

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Active chelating agent that has a high affinity for binding with iron.

Pharmacokinetics

Absorption

Bioavailability is 70%. Median time to T _max is approximately 1.5 to 4 h. C _max and AUC increase approximately linearly.

Distribution

Protein binding is approximately 99% and almost exclusively to serum albumin. Vd is approximately 14 L.

Metabolism

Major metabolic pathway is glucuronidation, with subsequent biliary excretion. Deferasirox is deconjugated in the intestine and undergoes enterohepatic recirculation.

Elimination

Primarily excreted in feces (84%) with minimal renal excretion (8%). Elimination t _½ ranges from 8 to 16 h.

Special Populations

In children younger than 6 yr of age, systemic exposure was approximately 50% lower than in adults.

Cl appears to be moderately lower (17.5%) in women than in men.

Has not been studied in patients with renal or hepatic function impairment.

Indications and Usage

Treatment of chronic iron overload caused by blood transfusions (transfusional hemosiderosis) in patients 2 yr of age and older.

Contraindications

Standard considerations.

Dosage and Administration

PO Start when patient has evidence of chronic iron overload and a serum ferritin consistently greater than 1,000 mcg/L. Initial dose is 20 mg/kg.

PO Adjust the dose as needed every 3 to 6 mo based on serum ferritin trends. Make dose adjustments in steps of 5 or 10 mg/kg based on patient's response and therapeutic goals. Consider interrupting therapy if serum ferritin consistently falls below 500 mcg/L. Dosage should not exceed 30 mg/kg/day.

Dose reduction, interruption, or discontinuation should be considered for increases in serum creatinine. If there is a progressive increase in serum creatinine beyond the age-appropriate ULN, interrupt deferasirox therapy. Once creatinine has returned to within the normal range, therapy may be restarted at a lower dose followed by gradual dose escalation. For adult patients, reduce the daily dose by 10 mg/kg if serum creatinine increases to more than 33% above the average of the pretreatment measurements at 2 consecutive visits, and if the increase cannot be attributed to other causes. For children, reduce the dose by 10 mg/kg if serum creatinine levels rise above the age-appropriated ULN at 2 consecutive visits.

General Advice

• Administer once daily on an empty stomach at least 30 min before food, preferably at the same time each day.
• Tablets are for suspension only. Do not chew or swallow whole.
• Calculate dose to the nearest whole tablet.
• Completely disperse tablet by stirring in water, orange juice, or apple juice until a fine suspension is obtained. Disperse doses less than 1 g in 3.5 oz of liquid, and disperse doses of 1 g or more in 7 oz of liquid. Drink suspension immediately.
• Resuspend any residue in a small volume of liquid and swallow.

Storage/Stability

Store between 59° to 86°F. Protect from moisture.

Drug Interactions

Avoid coadministration.

Do not coadminister because safety has not been established.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Pyrexia (19%); headache (16%); fatigue (6%).

Dermatologic

Rash (8%); urticaria (4%); leukocytoclastic vasculitis (postmarketing).

EENT

Nasopharyngitis (13%); pharyngolaryngeal pain (11%); pharyngitis (8%); acute tonsillitis, rhinitis (6%); ear infection (5%).

GI

Abdominal pain (14%); diarrhea (12%); nausea (11%); vomiting (10%); upper abdominal pain (8%).

Genitourinary

Acute renal failure (postmarketing).

Hematologic-Lymphatic

Cytopenias including agranulocytosis, neutropenia, and thrombocytopenia (postmarketing).

Hepatic

Hepatic failure, some with fatal outcome (postmarketing).

Hypersensitivity

Anaphylaxis and angioedema (postmarketing).

Lab Tests

Increased creatinine (38%); increased ALT (8%).

Musculoskeletal

Arthralgia (7%); back pain (6%).

Renal

Increased creatinine (11%).

Respiratory

Cough (14%); respiratory tract infection (10%); bronchitis (9%).

Miscellaneous

Influenza (11%).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 2 yr of age.

Elderly

Use with caution, usually starting at the low end of the dosage range because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Hypersensitivity

Serious hypersensitivity reactions (eg, anaphylaxis, angioedema) have been reported, with the onset of the reaction occurring in the majority of cases within the first month of treatment.

Renal Function

Dose-dependent increases in serum creatinine have been reported.

Hepatic Function

There have been postmarketing reports of hepatic failure, some with fatal outcome.

Special senses

Auditory disturbances (eg, decreased hearing, high-frequency hearing loss) and ocular disturbances (eg, cataract, elevations in IOP, lens opacities, retinal disorders) have been reported.

Overdosage

Symptoms

Diarrhea, hepatitis, nausea.

Patient Information

• Advise patient to take deferasirox once daily on an empty stomach at least 30 min prior to food, preferably at the same time each day.
• Advise patient not to chew or swallow the tablet whole.
• Instruct patient to completely disperse the tablet in water, orange juice, or apple juice, and to drink the resulting suspension immediately.
• Instruct patient to resuspend any residue in a small volume of liquid and swallow.
• Caution patient to not take deferasirox with aluminum-containing antacids.
• Caution patients that if they experience dizziness to exercise caution when driving or operating machinery.

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