Deferasirox

Uses

Deferasirox is used for the treatment of chronic iron overload due to blood transfusions in adult and paediatric patients (aged 2 years and over).

Deferasirox is also used to associated treatment for these conditions: Chronic Iron Overload

How Deferasirox works

Two molecules of deferasirox are capable of binding to 1 atom of iron. Deferasirox works in treating iron toxicity by binding trivalent (ferric) iron (for which it has a strong affinity), forming a stable complex which is eliminated via the kidneys.

Dosage

Deferasirox dosage

2 years children & Adult Dose:

Chronic Iron overload: Initially, 20 mg/kg daily. Adjust dosage every 3-6 months as needed based on trends in serum ferritin concentrations (monitor monthly). Adjust dosage in increments of 5 or 10 mg/kg daily (up to maximum dosage of 30 mg/kg daily) according to the patient’s clinical response and therapeutic goals. Consider temporarily interrupting therapy if serum ferritin concentrations are consistently <500 mcg/L.

Deferasirox must be taken once daily on an empty stomach at least 30 minutes before food, preferably at the same time each day. The tablets are dispersed by stirring in a glass of water or apple or orange juice (100 to 200 mL) until a line suspension is obtained. After the suspension has been swallowed, any residue must be resuspended in a small volume of water or juice and swallowed. The tablets must not be chewed or swallowed whole. Dispersion in carbonated drinks or milk is not recommended due to foaming and slow dispersion, respectively.

Completely disperse tab by stirring in water, orange or apple juice. Disperse 1 gm in 210 ml of liq. Following admin, any residue should be resuspended in a small vol of liq.

Side Effects

Serum creatinine increase, Abdominal pain, Nausea, Vomiting, Diarrhea, Proteinuria, Pyrexia, Headache, Cough , Nasopharyngitis, Pharyngolaryngeal pain, Influenza, Rash, Respiratory tract infection, Bronchitis, ALT increased, Arthralgia, back pain, Acute tonsillitis, Rhinitis, Fatigue, Ear infection, Transaminitis, Urticaria, Anaphylaxis, Angioedema, Cytopenias, including agranulocytosis, neutropenia and thrombocytopenia; leukocytoclastic vasculitis

Precaution

Moderate hepatic impairment. Children. Pregnancy and lactation.

Interaction

May chelate Al when used with Al-containing antacids. Decreased exposure with colestyramine and potent inducers of UGT enzymes (e.g. carbamazepine, rifampicin, phenytoin). May increase serum concentration of CYP1A2 (e.g. duloxetine, theophylline) and CYP2C8 (e.g. repaglinide, paclitaxel) substrates, and decrease serum concentrations of CYP3A4 substrates (e.g. ciclosporin, hormonal contraceptives, simvastatin).

Food Interaction

• Take at the same time every day.
• Take on an empty stomach. Take at least 30 minutes before food.
• Take separate from meals. Administration with food causes inconsistent bioavailability. May administer granules with a light meal, if necessary.

[Moderate] ADJUST DOSING INTERVAL: According to product labeling, the bioavailability of deferasirox was variably increased when taken with a meal.

MANAGEMENT: To ensure consistent plasma drug levels, deferasirox should be taken on an empty stomach 30 minutes before eating preferably at the same time everyday.

Deferasirox Drug Interaction

Moderate: diltiazem, diltiazem, acetaminophen, acetaminophenUnknown: ubiquinone, ubiquinone, glucose, glucose, metoprolol, metoprolol, metoprolol, metoprolol, nystatin topical, nystatin topical, valproic acid, valproic acid, pyridoxine, pyridoxine, phytonadione, phytonadione

Deferasirox Disease Interaction

Major: bone marrow suppression, dermatologic toxicities, hepatic impairment, renal dysfunctionModerate: auditory and ocular abnormalities, GI complication

Volume of Distribution

• 14.37 ± 2.69 L

Elimination Route

The absolute bioavailability (AUC) of deferasirox tablets for oral suspension is 70% compared to an intravenous dose.

Half Life

The mean elimination half-life ranged from 8 to 16 hours following oral administration.

Elimination Route

Deferasirox and metabolites are primarily (84% of the dose) excreted in the feces. Renal excretion of deferasirox and metabolites is minimal (8% of the administered dose).

Pregnancy & Breastfeeding use

Pregnancy: No clinical data on exposed pregnancies are available for deferasirox. Studies in animals have shown some reproductive toxicity at maternally toxic doses. The potential risk for humans is unknown. As a precaution, it is recommended that Deferasirox not be used during pregnancy unless clearly necessary.

Breast-feeding: In animal studies, Deferasirox was found to be rapidly and extensively secreted into maternal milk. No effect on the offspring was noted. It is not known if Deferasirox is secreted into human milk. Breast-feeding while taking Deferasirox is not recommended.

Contraindication

Creatinine clearance <40 mL/min or serum creatinine >2 times the age-appropriate upper limit of normal. High risk myelodysplastic syndrome (MDS) patients and patients with other hematological and non-hematological malignancies who are not expected to benefit from chelation therapy due to the rapid progression of their disease. Hypersensitivity to the active substance or to any of the excipients.

Special Warning

Dosage Modification for Adverse Renal Effects: Interrupt therapy if a progressive increase in SCR (Serum Creatinine Concentration) beyond the ULN occurs. Once SCR returns to within normal limits, reinitiate therapy at a lower dosage followed by gradual dosage escalation if clinical beneht is expected to outweigh potential risks. Reduce dosage by 10 mg/kg daily if SCR at 2 consecutive visits increases to a level >33% above the average pretreatment value and the increase cannot be attributed to other causes.

Dosage Modifcation for Adverse Hepatic Effects: Consider dosage adjustment or interruption of therapy in patients with severe, persistent, progressive, or unexplained elevations of liver function test results.

Acute Overdose

Single doses up to 40 mg/kg in normal subjects have been well tolerated. Acute signs of overdose may include nausea, vomiting, headache, and diarrhea. Overdose may be treated by induction of emesis or by gastric lavage, and by symptomatic treatment.

Storage Condition

Store at 25° C. Protect from moisture.

Innovators Monograph

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