Comprehensive Guide to Allopurinol: Uses, Dosage, Side Effects, and More

What is Allopurinol?

Overview of Allopurinol

Generic Name: Allopurinol

Brand Name: Zyloprim, Aloprim, Allohexal (Europe), generics

Drug Group: Xanthine oxidase inhibitor; antihyperuricemic agent

The drug is used to

• Manage chronic gout and prevent gout flares in adults.
• Treat uric acid nephropathy and urate kidney stones.
• Prevent tumor lysis syndrome in patients undergoing chemotherapy.
• Off-label uses include management of hyperuricemia in chronic kidney disease or Lesch-Nyhan syndrome under specialist guidance.

Key Characteristics

Form: Oral tablets (100 mg, 300 mg); IV injection (500 mg vial).

Mechanism: Inhibits xanthine oxidase, reducing uric acid synthesis from purines.

Approval: FDA-approved (1966 for Zyloprim, 1996 for Aloprim) and EMA-approved for hyperuricemia and gout.

Indications and Uses of Allopurinol

Allopurinol is indicated for:

Gout: Prevents recurrent gout attacks and manages chronic hyperuricemia in adults.

Uric Acid Kidney Stones: Dissolves and prevents urate stones in patients with high uric acid levels.

Tumor Lysis Syndrome: Reduces uric acid levels during chemotherapy for hematologic malignancies (e.g., leukemia, lymphoma).

Off-Label Uses: Treats hyperuricemia in chronic kidney disease, Lesch-Nyhan syndrome, or other rare metabolic disorders under specialist supervision.

Dosage of Allopurinol

Dosage for Adults

Gout and Hyperuricemia:

• Initial: 100 mg orally once daily.
• Maintenance: 200–300 mg/day (mild gout); 400–600 mg/day (moderate to severe), divided if >300 mg.
• Maximum: 800 mg/day.

Uric Acid Kidney Stones: 200–300 mg/day orally, adjusted based on urinary uric acid levels.

Tumor Lysis Syndrome (Oral): 600–800 mg/day for 2–3 days, divided into 2–3 doses.

Tumor Lysis Syndrome (IV, Aloprim): 200–400 mg/m²/day IV (maximum 600 mg/day), infused over 15–30 minutes.

Dosage for Children

Tumor Lysis Syndrome (≥6 Years):

• Oral: 10 mg/kg/day (maximum 800 mg/day), divided into 2–3 doses.
• IV: 200 mg/m²/day, adjusted for renal function.

Lesch-Nyhan Syndrome (Off-Label): 5–10 mg/kg/day, under specialist supervision.

Dosage for Pregnant Women

Pregnancy Category C: Limited data; use only if benefits outweigh risks, as animal studies suggest potential fetal harm. Consult a rheumatologist.

Dosage Adjustments

Renal Impairment:

• CrCl 10–20 mL/min: 200 mg/day.
• CrCl <10 mL/min: 100 mg/day or less frequent dosing (e.g., every 2 days).

Hepatic Impairment: Monitor closely; dose reduction may be needed.

Initiation: Start low (100 mg/day) and titrate slowly to minimize hypersensitivity risk.

Additional Considerations

• Take oral doses with food or water to reduce stomach upset.
• Ensure adequate hydration (2–3 L/day) to prevent uric acid crystallization.

How to Use Allopurinol

Administration:

• Oral: Take tablets with food or a full glass of water to improve tolerability.
• IV: Administered by healthcare professionals over 15–30 minutes for tumor lysis syndrome.

Timing: Take once daily or in divided doses, as prescribed; consistency aids uric acid control.

Missed Dose: Take as soon as remembered unless it’s nearly time for the next dose; do not double doses. Consult your doctor if multiple doses are missed.

Additional Tips:

• Avoid starting the drug during an acute gout flare; treat the flare first.
• Use prophylactic medications (e.g., colchicine, NSAIDs) for 3–6 months when initiating therapy to prevent flares.

Contraindications for Allopurinol

The drug is contraindicated in:

Patients with hypersensitivity to Allopurinol or its components, including those with a history of severe allergic reactions (e.g., Stevens-Johnson syndrome).

Patients with HLA-B*5801 allele (high risk of hypersensitivity) without genetic screening, especially in certain populations (e.g., Han Chinese, Thai).

Warnings & Precautions for Allopurinol

General Warnings

Hypersensitivity Syndrome: Risk of severe reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms). Screen for HLA-B*5801 in high-risk populations.

Liver Toxicity: May cause elevated liver enzymes or hepatitis; monitor liver function tests (LFTs) regularly.

Renal Impairment: Increased risk of toxicity; adjust doses and monitor renal function.

Bone Marrow Suppression: Rare risk of agranulocytosis, aplastic anemia, or thrombocytopenia; monitor complete blood count (CBC).

Use in Specific Populations

Pregnancy: Category C; avoid unless essential due to limited data. Use contraception during therapy.

Breastfeeding: Excreted in breast milk; use cautiously, weighing benefits against risks.

Elderly: Increased risk of renal impairment and hypersensitivity; start with lower doses.

Children: Safe for specific indications (e.g., tumor lysis syndrome) in children ≥6 years; specialist oversight required.

HLA-B*5801 Carriers: Higher risk of severe skin reactions; genetic testing recommended in Asian populations.

Additional Precautions

• Inform your doctor about kidney, liver, or allergic conditions before starting the treatment.
• Maintain hydration to reduce risk of kidney stones.

Overdose and Management of Allopurinol

Overdose Symptoms

Overdose is rare but may cause:

• Severe nausea, vomiting, or diarrhea.
• Kidney dysfunction or uric acid crystallization.
• Hypersensitivity reactions (e.g., rash, fever).

Immediate Actions

Contact Healthcare Provider: Seek medical advice immediately.

Supportive Care: Manage symptoms (e.g., fluids for dehydration, dialysis for renal failure).

Monitor: Check renal function, LFTs, and CBC for toxicity.

Additional Notes

• Overdose risk is low with proper dosing; store securely to prevent misuse.
• Report persistent symptoms promptly.

Side Effects of Allopurinol

Common Side Effects

• Rash (1–2%)
• Nausea or vomiting (1–2%)
• Diarrhea
• Elevated liver enzymes
• Drowsiness or headache
  These effects are usually mild and may resolve with continued use.

Serious Side Effects

Seek immediate medical attention for:

Hypersensitivity: Severe rash, fever, or signs of Stevens-Johnson syndrome (e.g., blistering, peeling skin).

Liver Toxicity: Jaundice, dark urine, or right-sided abdominal pain.

Bone Marrow Suppression: Unusual bruising, bleeding, or severe fatigue.

Renal: Decreased urine output or swelling.

Additional Notes

• Regular monitoring of LFTs, CBC, and renal function is essential.
• Report any skin changes immediately, especially in high-risk populations.

Drug Interactions with Allopurinol

The medication may interact with:

Azathioprine, Mercaptopurine: Increases toxicity due to xanthine oxidase inhibition; reduce purine analog doses by 50–75%.

Thiazide Diuretics (e.g., Hydrochlorothiazide): Increase hypersensitivity risk; monitor closely.

Warfarin: May enhance anticoagulant effects; monitor INR.

Theophylline: Increases theophylline levels; monitor for toxicity.

Ampicillin/Amoxicillin: Increases risk of rash; consider alternative antibiotics.

Patient Education or Lifestyle

Pharmacokinetics of Allopurinol

Absorption: Well-absorbed orally (~90%); peak plasma concentration of active metabolite (oxypurinol) at 1.5–4.5 hours.

Distribution: Volume of distribution is ~0.6 L/kg; oxypurinol widely distributed.

Metabolism: Rapidly metabolized to oxypurinol (active) via xanthine oxidase and aldehyde oxidase.

Excretion: Primarily renal (70% as oxypurinol); 10% unchanged Allopurinol.

Half-Life: Allopurinol: 1–2 hours; oxypurinol: 15–25 hours (prolonged in renal impairment).

Pharmacodynamics of Allopurinol

The drug exerts its effects by:

Inhibiting xanthine oxidase, reducing conversion of hypoxanthine and xanthine to uric acid.

Lowering serum and urinary uric acid levels, preventing gout flares and urate deposition.

Reducing oxidative stress from purine metabolism, protecting kidneys in tumor lysis syndrome.

Acting primarily via oxypurinol, which has a longer half-life and sustained activity.

Storage of Allopurinol

Temperature: Store oral tablets at room temperature (20–25°C or 68–77°F); IV vials at 2–25°C (36–77°F).

Protection: Keep in original container to protect from moisture and light.

Safety: Store out of reach of children to prevent accidental ingestion.

Disposal: Follow local regulations or consult a pharmacist for safe disposal of unused or expired medication.

Frequently Asked Questions (FAQs)

Q: What conditions does Allopurinol treat?
A: The drug treats gout, uric acid kidney stones, and tumor lysis syndrome.

Q: Can Allopurinol be started during a gout attack?
A: No, starting the medication during a flare may worsen symptoms; treat the flare first.

Q: Is Allopurinol safe for kidney disease patients?
A: Yes, with dose adjustments; monitor renal function closely.

Q: How long does Allopurinol take to work?
A: Uric acid levels drop within days, but gout flare prevention may take weeks to months.

Q: Can Allopurinol cause allergic reactions?
A: Yes, severe reactions like Stevens-Johnson syndrome are possible; seek immediate help for rashes.

Regulatory Information

The medication is approved by:

U.S. Food and Drug Administration (FDA): Approved in 1966 (Zyloprim) and 1996 (Aloprim) for gout and tumor lysis syndrome.

European Medicines Agency (EMA): Approved for hyperuricemia and gout-related conditions.

References

1. U.S. Food and Drug Administration (FDA). (2023). Zyloprim (Allopurinol) Prescribing Information.
   • Official FDA documentation detailing the drug’s approved uses, dosage, and safety for the USA.
2. European Medicines Agency (EMA). (2023). Allopurinol Summary of Product Characteristics.
   • EMA’s comprehensive information on the medication’s indications and precautions in Europe.
3. National Institutes of Health (NIH). (2023). Allopurinol: MedlinePlus Drug Information.
   • NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
4. World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Allopurinol.
   • WHO’s inclusion of Allopurinol as an essential medicine for gout and hyperuricemia.
5. Arthritis & Rheumatology. (2020). Allopurinol in the Management of Gout and Hyperuricemia.
   • Peer-reviewed article on the medication’s efficacy in gout (note: access may require a subscription).