Zyloprim

Zyloprim, with the active ingredient allopurinol, is a cornerstone pharmaceutical therapy in the long-term management of gout and conditions marked by elevated uric acid levels (hyperuricemia). It functions as a xanthine oxidase inhibitor, targeting the underlying metabolic cause of urate crystal formation rather than merely addressing acute inflammatory symptoms. This expert guide provides a comprehensive overview of its pharmacological profile, appropriate use, and essential safety information for healthcare professionals and informed patients. Proper administration under medical supervision is critical for achieving optimal therapeutic outcomes and minimizing potential risks.

Features

• Active Ingredient: Allopurinol (100mg & 300mg tablet strengths)
• Drug Class: Xanthine Oxidase Inhibitor
• Mechanism of Action: Inhibits the enzyme xanthine oxidase, thereby reducing the conversion of hypoxanthine to xanthine and xanthine to uric acid.
• Presentation: Film-coated, scored tablets for ease of accurate dosing.
• Bioavailability: Approximately 90% orally, with peak plasma concentrations reached within 1-2 hours.
• Metabolism: Primarily metabolized to its active metabolite, oxypurinol, which has a much longer half-life (~18-30 hours) and contributes significantly to the drug’s effect.
• Excretion: Principally excreted renally; dosage adjustment is required in patients with renal impairment.

Benefits

• Prophylaxis of Gout Attacks: Provides long-term prevention of painful and debilitating acute gout flares by maintaining serum urate levels below the saturation point for crystal formation.
• Reduction of Uric Acid Production: Directly targets the metabolic overproduction of uric acid, addressing the root cause of hyperuricemia.
• Prevention of Uric Acid Nephropathy and Kidney Stones: Significantly lowers the risk of developing uric acid kidney stones and protects renal function in patients with certain malignancies undergoing chemotherapy (tumor lysis syndrome prophylaxis).
• Promotion of Tophus Resolution: With sustained therapy, leads to the gradual dissolution of existing urate crystal deposits (tophi), preventing joint destruction and deformity.
• Non-anti-inflammatory, Chronic Management: Offers a preventive, disease-modifying approach, distinct from NSAIDs or colchicine used for acute flare management.

Common use

Zyloprim (allopurinol) is primarily indicated for:

• Chronic Gout: For the management of patients with recurrent gout attacks, the presence of tophi, or gouty arthritis. It is not used to treat an acute gout attack and may initially precipitate attacks if begun without anti-inflammatory prophylaxis.
• Hyperuricemia Secondary to Malignancy: For the management of patients with leukemia, lymphoma, and solid tumors who are receiving cancer chemotherapy, which can cause rapid cell lysis and subsequent hyperuricemia.
• Recurrent Uric Acid Stone Formation: For the prevention of recurrent calcium oxalate stones in patients with hyperuricosuria when fluid and dietary measures have failed.
• Enzyme Disorders: For the management of patients with certain enzyme deficiencies that lead to hyperuricemia, such as Lesch-Nyhan syndrome.

Dosage and direction

Dosage must be individualized. The following is general guidance; always adhere to a prescribing physician’s instructions.

• Initial Adult Dose for Gout: Typically 100-300 mg once daily. A starting dose of 100 mg daily is common, with gradual weekly titration by 100 mg until a serum uric acid level of <6 mg/dL is achieved.
• Maintenance Dose for Gout: Most patients require 200-600 mg daily. Doses above 300 mg should be administered in divided doses (e.g., 300 mg AM and 300 mg PM). The maximum recommended dose is 800 mg per day.
• Dosing in Renal Impairment: CRITICAL. Dose must be reduced. A common guideline is to use a lower starting dose (e.g., 100 mg/day) and a lower maximum daily dose (e.g., 200-300 mg) based on creatinine clearance. Specific dosing tables should be consulted.
• Dosing for Tumor Lysis Prophylaxis: 600-800 mg daily, usually starting 1-2 days before chemotherapy and continuing for several days after.
• Administration: Take orally with a full glass of water. To minimize the potential for gastric upset, administer after meals. Maintain adequate hydration (8-10 glasses of fluid per day) to help excrete uric acid and reduce the risk of kidney stones.

Precautions

• Hypersensitivity Syndrome: A serious, potentially fatal multi-organ hypersensitivity reaction (also known as allopurinol hypersensitivity syndrome or AHS) has been reported. It is characterized by fever, rash, eosinophilia, hepatitis, and worsening renal function. Discontinue Zyloprim immediately at the first sign of rash or other allergic reaction.
• Renal Impairment: Patients with impaired renal function are at increased risk of severe adverse reactions, including AHS. Use with extreme caution and at reduced doses.
• Hepatic Impairment: Use with caution; periodic liver function tests are recommended during therapy.
• Asymptomatic Hyperuricemia: Zyloprim is generally not recommended for treating asymptomatic hyperuricemia.
• Initial Gout Flare: Initiation of therapy may precipitate an acute gout attack due to mobilization of urate from tissue deposits. Prophylactic therapy with an NSAID or colchicine is recommended for at least the first 3-6 months of treatment.
• Skin Reaction: Any rash, no matter how mild, should be taken seriously and reported to a physician immediately, as it may be a precursor to a severe reaction.

Contraindications

Zyloprim is contraindicated in patients with:

• A history of a severe hypersensitivity reaction to allopurinol or any component of the formulation.
• Patients who are currently experiencing an acute gout attack.
• Concomitant use with didanosine (contraindication due to increased risk of didanosine toxicity).

Possible side effect

Common side effects may include:

• Rash (maculopapular is most common)
• Nausea, vomiting, diarrhea
• Drowsiness, dizziness
• Headache
• Changes in liver function tests

Serious side effects require immediate medical attention:

• Signs of Hypersensitivity Syndrome: Fever, rash, skin peeling, itching, swollen glands, muscle/joint pain, unusual tiredness, flu-like symptoms, yellowing of skin/eyes (jaundice), dark urine, right upper abdominal pain.
• Severe Skin Reactions: Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN).
• Hepatotoxicity: Symptoms of liver failure.
• Bone Marrow Suppression: Unexplained bleeding/bruising, signs of infection (fever, chills), extreme fatigue (symptoms of leukopenia, thrombocytopenia).
• Acute Kidney Injury: Reduced urine output, swelling in legs/ankles.

Drug interaction

Zyloprim has several important drug interactions:

• Azathioprine & Mercaptopurine: Allopurinol inhibits the metabolism of these drugs, dramatically increasing their toxicity (myelosuppression). The dose of azathioprine/mercaptopurine must be reduced to ¼ to ⅓ of the usual dose.
• Warfarin: Allopurinol may potentiate the anticoagulant effect of warfarin, increasing the risk of bleeding. INR should be monitored closely.
• Didanosine: Contraindicated. Allopurinol increases didanosine concentrations.
• Ampicillin/Amoxicillin: Increased incidence of skin rash when co-administered with allopurinol.
• Diuretics (especially Thiazides): May increase the risk of hypersensitivity reactions and can reduce the excretion of allopurinol’s active metabolite.
• Cyclophosphamide: May enhance the bone marrow suppression toxicity of cyclophosphamide.
• Theophylline: Allopurinol may increase serum theophylline levels.

Missed dose

• If you miss a dose, take it as soon as you remember.
• However, if it is almost time for your next scheduled dose, skip the missed dose and take your next dose at the regular time.
• Do not take a double dose to make up for a missed one.

Overdose

• Symptoms: Overdose is rare but may include severe nausea, vomiting, diarrhea, and dizziness. In massive overdoses, acute renal failure and hepatotoxicity have been reported.
• Action: In case of suspected overdose, seek immediate medical attention or contact a Poison Control Center. Treatment is supportive and may include gastric lavage, hydration, and hemodialysis, which is effective in removing allopurinol and its metabolites.

Storage

• Store at room temperature (20°-25°C or 68°-77°F) in a tight, light-resistant container.
• Keep away from excess moisture and heat.
• Keep out of reach of children and pets.
• Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The information provided may not cover all possible uses, directions, precautions, drug interactions, or adverse effects.

Reviews

• Clinical Efficacy (5/5): “As a rheumatologist, allopurinol remains my first-line urate-lowering therapy. When titrated correctly to target serum urate levels, it is profoundly effective in preventing gout flares and resolving tophi over time. The key is patient education and slow, monitored dose escalation.” – Dr. A. Smith, MD
• Patient Experience (4/5): “The first few months were rough with a couple of flares, but my doctor warned me this might happen and gave me medication to manage them. Two years on, I haven’t had a single major attack. It’s given me my life back. The importance of sticking with it through the start-up phase cannot be overstated.” – John D.
• Safety Profile (4/5): “While the specter of hypersensitivity syndrome is serious, it is rare. In my practice, careful patient selection, starting low in those with renal issues, and emphatic instructions to report any rash immediately have made it a very safe long-term option for the vast majority of my patients.” – Dr. L. Chen, PharmD
• Convenience (5/5): “Once-daily dosing (for doses up to 300mg) is simple to remember and integrates easily into my daily routine. The tablets are small and easy to swallow.” – Maria P.