DEFRATAJ - Full SmPC / Package Leaflet

DEFRATAJ contains the active substance deferasirox, an iron chelator. Iron chelators are medicines that bind to excess iron in the body so that it can be removed.

DEFRATAJ is used to treat chronic iron overload caused by frequent blood transfusions in patients with beta-thalassemia major, sickle-cell disease, myelodysplastic syndromes (MDS) and other transfusion-dependent anemias, in line with the prescribing information approved in your country.

Do not take DEFRATAJ if you:

• are allergic to deferasirox or any other ingredient;
• have severe kidney problems (creatinine clearance below 60 mL/min);
• are taking other iron-chelation therapies, unless specifically advised by a specialist.

Warnings and precautions

• Kidney problems: your doctor will check kidney function before and during treatment.
• Liver problems: liver enzymes will be monitored regularly.
• Skin reactions: serious skin reactions including SJS, TEN and DRESS have been reported. Stop treatment and seek urgent medical advice if you develop a severe rash, blisters or peeling skin.
• Stomach problems: rarely, ulcers or bleeding may occur, especially in elderly patients.
• Children, the elderly and patients with low blood-cell counts may need closer monitoring.

Other medicines and DEFRATAJ

Tell your doctor if you take aluminium-containing antacids, ciclosporin, simvastatin, oral contraceptives, theophylline, rifampicin, phenytoin, phenobarbital, ritonavir or any bile-acid sequestrant.

Pregnancy, breast-feeding and fertility

DEFRATAJ should not be used during pregnancy unless clearly necessary. Effective contraception is recommended. Speak to your doctor before breast-feeding.

Detailed Warnings & Precautions for Healthcare Professionals

Renal monitoring. Acute kidney injury, including cases requiring dialysis, has been reported. Establish baseline serum creatinine on two separate occasions before initiation. During the first month and after every dose escalation, measure creatinine weekly; thereafter, monthly. If creatinine rises above the age-appropriate upper limit of normal at two consecutive visits, reduce the dose by 10 mg/kg/day. Discontinue if the rise persists or if proteinuria is detected. Annual screening for proximal tubulopathy (Fanconi syndrome) is recommended in long-term paediatric use.

Hepatic monitoring. Measure serum transaminases, bilirubin and alkaline phosphatase before initiation, every two weeks during the first month, and monthly thereafter. Hepatic failure - including fatal cases - has been reported, predominantly in patients with significant comorbidity, advanced age or pre-existing cirrhosis. Avoid in severe hepatic impairment (Child-Pugh C); use with caution and at reduced dose in moderate impairment (Child-Pugh B).

Severe Cutaneous Adverse Reactions (SCAR). Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), DRESS syndrome and erythema multiforme have been reported. Counsel patients to seek immediate medical attention for any new rash, mucosal involvement, fever or systemic symptoms. Permanently discontinue deferasirox if SCAR is suspected and consider lifelong avoidance.

Gastro-intestinal events. Upper gastro-intestinal ulceration, haemorrhage and perforation have been reported. Use caution in patients with active peptic ulcer disease, anticoagulant therapy, or NSAID/corticosteroid co-medication.

Auditory and visual disturbances. High-frequency hearing loss and lens opacities have been reported in long-term use. Perform baseline and annual audiometry and ophthalmologic examination, particularly in paediatric patients.

Haematological monitoring. Cytopenias have been reported, particularly in pre-existing MDS or advanced disease. Discontinue deferasirox if unexplained cytopenia develops; resumption may be considered after recovery, with reduced dose.

Always take this medicine exactly as your doctor has told you.

How to disperse and take

1. Add the tablet(s) to a glass of water, orange juice or apple juice (~100-200 ml).
2. Stir until fully dispersed.
3. Drink the suspension immediately.
4. Rinse the glass with extra liquid and drink that as well.

When to take it

Take once daily, on an empty stomach, at least 30 minutes before food, at the same time every day. Do not crush or chew the tablets.

If you take more than you should

Contact your doctor or nearest emergency department immediately. Take the medicine pack with you.

If you forget to take a dose

Take it as soon as you remember on the same day, then continue the normal schedule. Do not double the next dose.

Detailed Dosing Guidance for Healthcare Professionals

Administration: disperse the tablet in a glass of water, orange juice or apple juice (100-200 mL for Ôëñ 1 g doses; 200-300 mL for higher doses) by stirring until a fine suspension is obtained. Drink immediately. Re-suspend any residue in a small additional volume and drink that as well. Take at least 30 minutes before food, preferably first thing in the morning, at the same time each day to minimise food-related variability in absorption.

Dose interruption: consider interruption when serum ferritin consistently falls below 500 ng/mL to avoid over-chelation; resume with reduced dose when ferritin rises above 1000 ng/mL or per protocol.

Missed dose: if missed by less than 12 hours, take as soon as remembered with the next-day dose at the usual time; if greater than 12 hours, omit and resume the schedule.

Switching from another chelator: when transitioning from deferoxamine, allow a 48-hour washout. From deferiprone, no washout is required but baseline labs must be re-established.

Like all medicines, DEFRATAJ can cause side effects, although not everybody gets them.

Stop taking DEFRATAJ and seek urgent medical attention if you notice:

• severe rash, blisters, peeling skin or sores in the mouth (signs of SJS / TEN / DRESS);
• signs of allergic reaction (swelling of face/tongue, difficulty breathing);
• black/tarry stools or vomiting blood;
• greatly reduced urine output, leg swelling, severe tiredness (kidney failure);
• yellowing of skin or eyes (liver problems).

Common side effects

• Nausea, vomiting, diarrhoea, abdominal pain;
• Mild rash;
• Increases in serum creatinine and liver enzymes (laboratory finding).

Reporting: report side effects to your doctor or to pharmacovigilance@tajpharma.com.

Adverse Reaction Frequency Categories (CIOMS / EMA)

Adverse reactions are listed by MedDRA System Organ Class and frequency: very common ( 1/10), common ( 1/100 to < 1/10), uncommon ( 1/1,000 to < 1/100), rare ( 1/10,000 to < 1/1,000), very rare (< 1/10,000), and not known (cannot be estimated from available data).

Pharmacovigilance reporting. Healthcare professionals are asked to report any suspected adverse reactions to the national pharmacovigilance authority and/or to Taj Pharma at pv@tajpharma.com. Reporting suspected adverse reactions after authorisation of the medicinal product is important and allows continued monitoring of the benefit/risk balance.

• Keep out of the sight and reach of children.
• Do not use after the expiry date stated on the carton.
• Store below 30 degrees C, in the original blister, protected from moisture.
• Do not throw away medicines via wastewater or household waste.

What DEFRATAJ contains

The active substance is deferasirox. Each dispersible tablet contains 100, 125, 250, 400 or 500 mg of deferasirox.

Other ingredients: lactose monohydrate, microcrystalline cellulose, crospovidone, povidone K30, sodium lauryl sulfate, colloidal silicon dioxide, magnesium stearate.

What DEFRATAJ looks like and contents of the pack

Off-white to pale yellow, round, uncoated dispersible tablets with a break-line. PVC/PVDC-Aluminium blisters of 10 x 10 tablets; HDPE bottles and custom pack sizes available. Not all pack sizes may be marketed.

Marketing Authorisation Holder & Manufacturer

Taj Pharma India Ltd., Plot Sarigam GIDC, Sarigam, Gujarat, India.