Deferasirox说明书

Instructions

Product name Enrig

Generic name Deferasirox dispersible tablets

The main ingredient is deferasirox.

Indications: It is used to treat chronic iron overload in patients with beta-thalassemia older than 6 years old due to frequent blood transfusions (monthly administration of concentrated red blood cells ≥7mL/kg).

Adverse reactions include gastrointestinal dysfunction, rash, mild elevation of serum creatinine and transaminases.

Contraindications 1. It is prohibited for those who are known to be allergic to the active ingredients or any excipients.

2. It should not be used in combination with other iron chelation treatments because the safety of such combined use has not been established.

3. It is prohibited to be used in patients with creatinine clearance <40mL/min or serum creatinine >2 times the upper limit of normal for the corresponding age; patients with poor general condition, high-risk myelodysplastic syndrome (MDS) or advanced malignant tumors; patients with platelet count <50x109/L.

Precautions 1. Use with caution in elderly patients with reduced liver and kidney function, pregnant and lactating women, and children under 6 years old. Not suitable for use by children under 2 years old.

2. During the medication period, liver and kidney function indicators, platelet count, hearing and vision need to be monitored regularly.

Pregnant and lactating women should use this medication with caution.

Pediatric Medication: Children under 6 years of age should use Enrego with caution. Not suitable for use by children under 2 years old.

Medication for the elderly should be used with caution.

Drug interactions: Avoid combination with strong inducers of UDP-glucuronosyltransferase (UGT) (such as rifampicin, phenytoin, sedatives and hypnotics, protease inhibitors), cholestyramine.

Do not administer concurrently with aluminum-containing antacids. Not to be combined with other iron chelation treatments.

Be careful with repaglinide, drugs with potential ulcerogenic effects such as NSAIDs, cortisones, or oral bisphosphonates, drugs metabolized by CYP3A4 (such as cyclosporine, simvastatin, hormonal contraceptives). Withhold Enrig at least 5 days before performing Gallium-67 imaging.

Overdose Cases of overdose (taking 2-3 times the prescribed amount for several weeks) have been reported. One case report reported that an overdose resulted in subclinical hepatitis, which resolved after discontinuation of the drug, with no long-term effects.

Thalassemia patients with iron overload can tolerate a single dose of 80 mg/kg with only mild nausea and diarrhea.

A single dose of 40 mg/kg was well tolerated by healthy volunteers.

Signs of acute overdose include nausea, vomiting, headache, and diarrhea. Treatment of overdose includes induction of vomiting, gastric lavage, and symptomatic treatment.

Drug Toxicology Deferasirox is an oral active chelating agent that is highly selective for iron (Fe3+). It is a ligand with 3 protrusions that binds iron with high affinity in a 2:1 ratio.

Although deferasirox has a very low affinity for zinc and copper, serum concentrations of these trace metals decreased to varying degrees after administration. The clinical significance of these reductions in metal concentrations is unclear.

Repeated Dose Toxicity: The main findings in long-term toxicity studies were nephrotoxicity, bile duct changes, and lens opacification (cataracts).

Reproductive Toxicity, Genotoxicity, Carcinogenicity: There is no evidence of adverse effects on fertility and reproduction in male and female rats at daily oral doses of deferasirox up to 75 mg/kg (equivalent to 0.6 times the MRHD calculated as mg/m2).

Pharmacokinetics 1. Absorption: After oral administration of deferasirox, the time to peak (Tmax) is approximately 1.5-4 hours.

(1) The absolute bioavailability (AUC) of deferasirox tablets is 73.5±12.8%. Both the Cmax and AUC of deferasirox increase approximately linearly with dose after a single dose and under steady-state conditions.

(2) After multiple doses, the exposure level of deferasirox increased, with an accumulation factor of 1.3-2.3. The absolute bioavailability (AUC) of deferasirox orally dispersible tablets is approximately 70% of intravenous administration.

(3) When taken with a high-fat breakfast (fat content > 50% of total calories), the total exposure (AUC) increases approximately 1-fold; when taken with a standard breakfast, the total exposure (AUC) increases by approximately 50%.

(4) The bioavailability (AUC) of deferasirox is moderately increased (approximately 13-25%) when taken 30 minutes before a meal with a normal or high-fat meal.

2. Distribution: Deferasirox is highly bound to plasma proteins (about 99%), and is almost exclusively bound to serum albumin. The steady-state distribution volume (Vss) in adults is 14.37±2.69 liters.

Storage Moisture-proof, sealed and stored below 30°C, out of reach of children.