Chelova

Approved Indications:

• Chronic Iron Overload due to Blood Transfusions:
• In patients aged ≥2 years with transfusion‑dependent anemias (e.g., β‑thalassemia, sickle cell disease, myelodysplastic syndromes), to reduce iron overload when chelation therapy is indicated.
• Non‑transfusion‑dependent Thalassemia with Iron Overload:
• In patients aged ≥10 years with chronic iron overload (LIC ≥5 mg Fe/g dry weight) who require chelation.

Clinically Accepted Off-label Uses:

• Iron overload in hereditary hemochromatosis when phlebotomy is not feasible.
• Iron overload in other chronic anemias treated with chronic transfusion support.
• Occasional use in pediatric patients <2 years in specialized centers.

Adults and Pediatrics (≥2 years):

• Initial Dose (Transfusional Iron Overload):
• 20 mg/kg once daily by mouth, taken on an empty stomach or with a light meal.
• Dose Adjustment:
• If serum ferritin remains ≥1000 ng/mL after 3 months, dose may be increased in increments of 5 or 10 mg/kg to a maximum of 30 mg/kg/day.
• If ferritin falls below 500 ng/mL or LIC decreases below target, dose reduction recommended.

Non‑transfused Thalassemia:

• Initial dose usually 10 mg/kg/day, titrated up to 20 mg/kg/day based on LIC and ferritin.

Pediatrics (<2 years):

• Not routinely recommended; use only in specialist centers with pharmacokinetic monitoring.

Renal Impairment (eGFR <40 mL/min):

• Start at lowest dose (10 mg/kg/day); monitor serum creatinine and electrolytes twice weekly during initial therapy.

Hepatic Impairment:

• No formal dose adjustment but use caution in moderate to severe impairment; monitor liver enzymes.

Elderly:

• No specific adjustment; monitor renal and hepatic function.

Deferasirox is an orally active, once‑daily iron chelator that binds free iron in plasma (trivalent Fe³⁺) in a 2:1 molar ratio. The resulting complex is excreted primarily via bile into the feces. By reducing labile plasma iron and non‑transferrin‑bound iron, deferasirox decreases iron deposition in vital organs (liver, heart, endocrine glands), preventing oxidative injury from iron-mediated radicals and preserving organ function.

Absorption:

• Peak plasma concentration occurs ~1–2 hours after administration; absorption is decreased by food—preferably taken fasting or with light meal.

Distribution:

• Volume of distribution ~14 L; highly protein-bound (≈99%).

Metabolism:

• Primarily glucuronidated by UGT1A1 and UGT1A3; minor CYP-mediated metabolism.

Active Metabolite:

• Deferasirox glucuronide is pharmacologically inactive.

Elimination:

• Excreted mainly via feces (~83%); ~8% excreted in urine.
• Elimination half-life typically 8–16 hours in patients with normal renal function.

• Pregnancy:
• FDA Category C. Animal studies have shown embryotoxicity at high doses; no adequate human data. Use only if potential benefit outweighs risk.
• Lactation:
• It is unknown whether deferasirox is excreted in human milk. Due to potential for adverse effects, breastfeeding is not recommended during treatment.
• Caution:
• Data are limited; treatment decisions should weigh maternal benefits versus potential infant risk.

• Primary Class: Iron chelator
• Subclass: Tridentate, oral iron chelator

• Known hypersensitivity to deferasirox or any excipients.
• Baseline serum creatinine >2.5 mg/dL (220 µmol/L) in adults or doubling of creatinine on therapy.
• Thrombocytopenia (platelet count <50 × 10⁹/L) due to bleeding risk.
• Active hepatic failure (Child‑Pugh C).
• Severe neutropenia (<1.0 × 10⁹/L) with concurrent febrile illness.

• Renal Toxicity: Monitor serum creatinine and urinalysis before treatment and at least monthly. Early signs: increasing creatinine or proteinuria.
• Hepatotoxicity: Monitor liver enzymes regularly; discontinue if ALT/AST >5× ULN or with jaundice.
• Gastrointestinal Ulceration and Bleeding: Rare cases reported—watch for abdominal pain, dysphagia, melena.
• Hematologic Effects: Monitor CBC monthly for cytopenias; rare agranulocytosis or thrombocytopenia may occur.
• Auditory and Ocular Toxicity: Perform baseline and periodic evaluations—reports of hearing loss, lens opacities.
• Infections: Immunocompromised patients may have increased infection risk; monitor WBC counts.

Common (≥10%):

• Gastrointestinal: nausea, diarrhea, abdominal pain, vomiting
• Skin reactions: rash
• Mild increases in serum creatinine

Less Common (1–10%):

• Headache
• Pruritus
• Elevated ALT/AST
• Proteinuria

Serious/Rare (<1%):

• Renal failure
• Hepatic failure
• GI hemorrhage or ulceration
• Agranulocytosis or thrombocytopenia
• Hearing loss or visual impairment

Timing:

• GI effects often occur early and may diminish over time.
• Renal or hepatic toxicity may appear within weeks to months; monitoring required throughout therapy.

• UGT Inducers/inhibitors: May alter deferasirox metabolism—e.g., rifampin (inducer) may reduce levels; atazanavir (UGT2B7 inhibitor) may increase levels.
• Chelation with multivalent cations (e.g., aluminum, calcium, magnesium supplements): May bind deferasirox—administer ≥2 hrs apart.
• Concomitant nephrotoxins (e.g., NSAIDs): Increased renal toxicity risk.
• Concurrent hepatotoxic drugs (e.g., bosentan): Monitor liver function closely.
• Antacids: May delay absorption; take deferasirox fasting.

• 2023–2024 expert consensus guidelines continue to recommend deferasirox as a first‑line oral chelator in transfusion‑dependent thalassemia and MDS.
• WHO Essential Medicines List includes deferasirox for iron overload.
• FDA updates emphasize rare but serious risks of gastrointestinal necrosis and renal failure; prescribing information now highlights intensified early monitoring.
• International thalassemia societies recommend lower starting doses in elderly and renal‑impaired patients, along with more conservative targets for serum ferritin (< 500 ng/mL) and liver iron concentration (LIC <7 mg Fe/g dry weight).

• Store at 20 °C to 25 °C (68 °F to 77 °F).
• Protect from moisture and light; keep in original container with desiccant.
• Stability:
• Tablets are hygroscopic—seal tightly after use and consume within 30 days of opening bottle.
• Handling Precautions:
• Wash hands before and after handling tablets.
• Avoid crushing or chewing; swallow whole.
• No refrigeration required.