Deferasirox

BRAND NAMES:

Exjade—The active ingredient is deferasirox, which is available in the form of oral suspension tablets called Exjade Deferasirox.

Jadenu - Jadenu deferasirox tablets are available for oral use and are used to treat patients with chronic iron overload.

Jadenu sprinkles—These come in the form of granules for oral use and help remove excess iron from the body. 

MECHANISM OF ACTION:

Deferasirox is used in the management of iron overload in patients. Deferasirox chelates non-transferrin-bound iron, iron in transit between transferrin ferritin and hemosiderin. Deferasirox can directly bind and remove iron from myocardial cells. It will not bind iron-bound molecules such as transferrin, hemoglobin, or cytochromes. A small amount of iron is available from chelation at any given time. Although this is a small fraction of total body iron, it has a profound effect. The resultant ferrioxamine is very water-soluble. If chelation occurs in hepatocytes, the compound will be excreted in bile; when chelation occurs with free iron in plasma or other tissues, it is excreted by the kidneys and then excreted via urine. It can also bind aluminum within the plasma to form aluminoxane, which is renally excreted.

PHARMACOKINETICS:

Absorption: Deferasirox tablets for oral suspension have a 70% bioavailability compared to intravenous doses. 

 Distribution: 14.37 ± 2.69 L. 

 Metabolism: In humans, deferasirox's oxidative metabolism appears minor, mediated by CYP450. The main metabolic pathway is glucuronidation, which leads to biliary excretion. 

 Excretion: 84% of the primary dose is excreted through feces, with minimal renal excretion of deferasirox and its metabolites.

 PHARMACODYNAMICS:

It is an orally active chelator that is selective for iron. It has a capacity that binds iron with high affinity in a 2:1 ratio and a very low affinity for zinc and copper, which are variable decreases in the serum concentration of these trace metals after the administration of deferasirox.

DOSAGE AND STRENGTH:

These are available in tablets, granules, and tablets for oral suspension. The amount of medicine described depends on the strength of the medicine, and number of doses, and the time allowed between doses.

For chronic iron overload after blood transfusions, 

• The oral dosage forms of granules and tablets in adults and children above 2 years are recommended to take a dosage starting from 14mg/Kg of the body weight per day. The dose will not be increased by more than 28mg/kg once a day. 
• The oral dosage form of tablet for suspension in adults or children above 2 years, the starting dose will be 20mg/kg of the body weight per day. The dosage can be adjusted to 40 mg/kg per day.

For chronic iron overload in non-transfusion-dependent thalassemia syndrome, 

• For the oral dosage forms of tablets and granules for adults and children above years the recommended starting dose will be from 7mg/kg of body weight per day and do not exceed 14mg/kg per day. 
• The oral tablets for suspension in adults and children above 10 years will be recommended 10mg/kg of the body weight per day, and the dose should not exceed 20mg/kg per day.

Tables for suspension should always be dissolved in liquid before ingesting. After completely dissolving the tablet in the liquid, the mixture thickens and should be drunk immediately.

If you miss your dose, take it as soon as possible. If it is time for the next dose, omit the missed dose and stick to the normal scheduled dose.

CONTRAINDICATIONS:

Deferasirox is contraindicated to hypersensitivity, renal OR liver failure, kidney disease, bone marrow, and thrombocytopenia.

DRUG INTERACTIONS:

As certain drugs should not be used together, discuss with a physician the drugs that were already taken for other treatments. If it is compulsory to take those drugs with deferasirox, then the dosage will be changed according to the patient's condition. Below are the few drugs mentioned that should be avoided with Deferasirox.

• Aspirin
• Aluminium hydroxide
• Busulfan,
• Repaglinide
• Theophylline
• Paracetamol
• Diltiazem
• Celecoxib
• Amiodarone
• Duloxetine
• Ritonavir
• Enzalutamide
• Daprodustat
• Colestinol
• Resmetirom

FOOD INTERACTIONS:

Administration of food causes inconsistent bioavailability. Take on an empty stomach. Take at least 30 minutes before food.

ADVERSE EFFECTS:

• Blurred vision
• Dizziness
• Stomach pain
• Nausea
• Voice changes
• Earache
• Skin rashes
• Increase in serum creatinine
• Bleeding gums
• Black tarry stools
• Blood vomiting
• Bleeding gums
• Dark urine
• Pale skin
• Lower back or side pain
• Change in hearing and vision

OVERDOSE:

• Symptoms of overdose include
• Loss of appetite
• Lack of energy
• Diarrhea
• Unusual bruising or bleeding
• Yellowing of the skin or eyes
• Decreased urination
• Swelling of legs or ankles

TOXICITY:

Medication should be taken as prescribed by the doctor. Avoid in the cases of pregnancy and breastfeeding.

STORAGE:

Store the medicine at room temperature in a closed container. Keep away from heat, direct sunlight, and moisture. Do not keep outdated medicine for a longer time.