Esloric 100 mg

Indication:

Esloric 100 mg is indicated for the treatment of-

• Gout and Gouty Arthritis: Prevention and long-term management of primary and secondary gouty attacks, tophi, joint destruction, and uric acid nephropathy.
• Tumor Lysis Syndrome (TLS) Prevention: Prophylaxis and treatment of hyperuricemia in patients receiving chemotherapy or radiation therapy for leukemia, lymphoma, or other malignancies, where rapid cell turnover elevates systemic purine release.
• Recurrent Calcium Oxalate Renal Calculi: Prevention of recurrent calcium oxalate or uric acid kidney stone formation in patients with hyperuricosuria (excessive urinary excretion of uric acid).
• Enzyme Deficiencies: Management of hyperuricemia associated with genetic disorders such as Lesch-Nyhan syndrome or glucose-6-phosphatase deficiency.

”রেজিস্ট্রার চিকিৎসকের পরামর্শ অনুযায়ী ঔষধ সেবন করুন”

Dogase & Adminstration:

Adult Dosage (Age 18 Years and Older)

• Mild Gout Treatment: 100 mg to 300 mg orally once daily.
• Moderately Severe to Severe Tophaceous Gout: 400 mg to 600 mg orally once daily. (Doses above 300 mg should be administered in divided doses, e.g., 300 mg twice daily, to limit gastrointestinal irritation).
• Chemotherapy-Induced Hyperuricemia (TLS): 600 mg to 800 mg orally daily in divided doses, starting 1 to 2 days before chemotherapy begins.
• Recurrent Calcium Oxalate Stones: 200 mg to 300 mg orally once daily.
• Renal Impairment Dosage Adjustments (Crucial to Prevent Toxicity):
  • Creatinine Clearance (CrCl) 10–20 mL/min: Max 200 mg/day.
  • CrCl <10 mL/min: Max 100 mg/day (or 100 mg every alternative day).

Pediatric Dosage (Under 18 Years)

• Chemotherapy-Induced Hyperuricemia (TLS) Only:
  • Children <6 years: 150 mg orally daily in three divided doses.
  • Children 6 to 10 years: 300 mg orally daily in three divided doses.
  • Alternative Weight-Based Dosing: 10 mg/kg/day orally in 3 divided doses (Maximum: 600 mg/day).

Administration Instructions

• With Food: Allopurinol should be taken immediately after a meal to minimize gastrointestinal upset.
• Adequate Hydration: Patients must maintain a high fluid intake. Instruct patients to drink at least 2 to 2.5 liters of water daily to ensure an adequate urine output, which prevents the precipitation of xanthine or uric acid crystals in the kidneys.
• Acute Gout Flare Prophylaxis: Initiation of allopurinol can paradoxically precipitate an acute gouty attack due to mobilization of urate from tissue stores. Therefore, co-administer a low-dose NSAID or Colchicine for at least 1 to 3 months when starting allopurinol.

”রেজিস্ট্রার চিকিৎসকের পরামর্শ অনুযায়ী ঔষধ সেবন করুন”

Pharmacology:

• Mechanism of Action: Allopurinol is a structural analogue of the naturally occurring purine base hypoxanthine. It is a potent, orally active xanthine oxidase inhibitor.
  • Enzymatic Blockade: Allopurinol and its primary active metabolite, oxypurinol (alloxanthine), bind to and inhibit the enzyme xanthine oxidase. This enzyme is responsible for the sequential oxidation of hypoxanthine to xanthine, and subsequently xanthine to uric acid (the end-product of purine metabolism in humans).
  • Purine Pathway Shunting: By blocking xanthine oxidase, allopurinol decreases both serum and urinary concentrations of uric acid. This halts the supersaturation of uric acid in bodily fluids, thereby stopping the deposition of monosodium urate crystals in joints and tissues, and preventing the formation of calcium oxalate/uric acid renal calculi.
  • Feedback Inhibition: The accumulation of hypoxanthine and xanthine triggers a reutilization pathway, converting them back into adenosine and guanosine monophosphates via hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This leads to a de novo feedback inhibition of purine synthesis.
• Pharmacokinetics:
  • Absorption: Rapidly absorbed from the upper gastrointestinal tract after oral administration, reaching peak plasma concentrations within 1.5 hours. It has an oral bioavailability of approximately 67% to 90%.
  • Distribution: Virtually unbound to plasma proteins. It is widely distributed throughout body tissues, except in the brain, where its concentrations are low.
  • Metabolism & Elimination: Approximately 70% of allopurinol is rapidly metabolized in the liver by xanthine oxidase itself to its major pharmacologically active metabolite, oxypurinol. Allopurinol has a short plasma half-life (t1/2​) of about 1 to 2 hours, whereas oxypurinol has a much longer terminal half-life of 15 to 30 hours, which is primarily responsible for the sustained, once-daily clinical efficacy of the drug. Elimination is mainly renal (approx. 70% as oxypurinol and 10% as unchanged allopurinol), while the remainder is excreted in the feces.

Side Effects:

• Common: Skin rash (maculopapular), nausea, vomiting, diarrhea, abdominal pain, and transient elevations in liver enzymes.
• Serious: Allopurinol Hypersensitivity Syndrome (AHS) (a rare but life-threatening reaction presenting with fever, severe exfoliative dermatitis such as Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis, vasculitis, hepatitis, acute interstitial nephritis, and eosinophilia), bone marrow suppression (leukopenia, thrombocytopenia), and hepatotoxicity.

Drug Interaction:

• 6-Mercaptopurine (6-MP) & Azathioprine: These cytotoxic drugs are metabolized by xanthine oxidase. Co-administration with allopurinol dramatically increases their blood levels and bone marrow toxicity. The dose of 6-MP or azathioprine must be reduced to 25% to 33% of their usual dose.
• Amoxicillin & Ampicillin: Concomitant use increases the risk of developing a drug-induced skin rash.
• Warfarin and Coumarin Anticoagulants: Allopurinol may prolong the half-life of anticoagulants. Monitor INR closely and adjust anticoagulant doses accordingly.
• Thiazide Diuretics: May increase oxypurinol levels and the risk of severe allopurinol hypersensitivity, particularly in patients with renal impairment.

Pregnancy & Lactation:

• Pregnancy: Category C. There is insufficient clinical evidence regarding safety in pregnant women. Allopurinol should be used during pregnancy only when there is no safer alternative and the disease itself carries a high risk for the mother or fetus.
• Lactation: Allopurinol and oxypurinol are excreted in human breast milk. Breastfeeding is not recommended while taking allopurinol due to potential risks to the infant.

Over Dosage:

• Symptoms: Nausea, vomiting, diarrhea, dizziness, oliguria, and hematuria.
• Treatment: No specific antidote exists. Treatment is symptomatic and supportive. Administer abundant oral or intravenous fluids to maintain high urine output and promote excretion of both allopurinol and oxypurinol. Hemodialysis may be utilized in severe cases since both compounds are dialyzable.

Therapeutic Class:

Antigout Agent; Xanthine Oxidase Inhibitor

Storage Conditions:

Store below at 30°C  temperature in a dry place. Away from light and out of reach of children. Do not use the medication after its expiration date.