ZynolTab 300 Mg 20’s Potential Overview:

Brand Name: ZynolTab
Generic Name: Allopurinol
Strength: 300 mg
Pack Size: 20 Tablets

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ZynolTab (Allopurinol) 300 mg is a medication used to lower elevated uric acid levels, primarily for managing chronic gout and preventing uric acid kidney stones. It works by inhibiting the enzyme xanthine oxidase, reducing uric acid production in the body.

Mechanism of Action (MOA):

• ZynolTab (Allopurinol) works by inhibiting xanthine oxidase, an enzyme involved in the conversion of purines to uric acid. By blocking this enzyme, allopurinol decreases the production of uric acid.
• Uric acid is responsible for the formation of urate crystals, which cause inflammation in joints (as in gout) and can lead to kidney stone formation. By reducing uric acid levels, ZynolTab prevents the formation of these crystals, helping to manage gout, hyperuricemia, and uric acid-related kidney stones.

Indications:

ZynolTab (Allopurinol) 300 mg is primarily used for the following conditions:

1. Gout:
   • Chronic gout management to reduce serum uric acid levels and prevent gout flares or urate crystal deposits in joints.
2. Hyperuricemia:
   • Treatment of hyperuricemia associated with chemotherapy or radiation therapy in patients with certain cancers like leukemia, which can increase the breakdown of purines and the production of uric acid.
3. Kidney Stones:
   • Prevention of uric acid nephrolithiasis (uric acid kidney stones) by reducing uric acid levels in the urine.
4. Other Purine Metabolism Disorders:
   • Conditions that cause excessive purine breakdown and elevated uric acid levels.

Dosage:

• Adults:
  • Initial dose: 100 mg to 300 mg once daily, depending on the severity of the condition and the patient’s uric acid levels.
  • The dose can be gradually increased to up to 800 mg daily for chronic gout management or hyperuricemia, depending on patient response and tolerability.
  • Maintenance dose: Generally between 200 mg and 300 mg per day, but higher doses may be required for more severe cases.
• Renal Impairment:
  • Dosage should be reduced in patients with renal insufficiency or impaired kidney function, with adjustments made based on creatinine clearance or serum creatinine levels.
• Pediatric patients:
  • Dosing is based on the child’s body weight, with an initial dose typically starting around 50 mg/day and adjusted as needed.

Side Effects:

Common Side Effects:

• Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhea, or mild indigestion.
• Skin reactions: Rash, itching, and occasionally more severe reactions like exfoliative dermatitis or Stevens-Johnson syndrome.
• Headache: Some patients may experience headaches or dizziness.
• Drowsiness: Fatigue or drowsiness may occur in some patients.

Serious Side Effects (requiring medical attention):

• Severe allergic reactions: Rash, fever, lymphadenopathy, eosinophilia, liver dysfunction, or renal failure.
• Hepatotoxicity: Elevated liver enzymes or jaundice.
• Severe skin reactions: These include conditions like Stevens-Johnson syndrome or toxic epidermal necrolysis, which are life-threatening.
• Renal failure: Particularly in patients with pre-existing renal dysfunction, dehydration, or who are on high doses of allopurinol.

Precautions:

• Renal Impairment:
  • Dose adjustment is necessary for patients with renal dysfunction. Allopurinol is excreted by the kidneys, and impaired renal function can lead to an increased risk of drug accumulation and toxicity.
• Liver Disease:
  • Caution is advised in patients with liver disease. Monitor liver function regularly, as allopurinol can cause hepatotoxicity in rare cases.
• Hydration:
  • Ensure adequate hydration during therapy to reduce the risk of uric acid crystal formation in the kidneys.
• Allergic Reactions:
  • If any signs of skin rash, fever, or other allergic symptoms appear, discontinue the medication immediately and consult a healthcare provider.
• Acute Gout Flares:
  • ZynolTab (Allopurinol) is not used for treating acute gout attacks. Instead, it is used for chronic management. Starting allopurinol during an acute attack may actually exacerbate the flare.
• Pregnancy:
  • Allopurinol should be used during pregnancy only if clearly needed and after assessing the benefits versus risks. It is classified as Category C in pregnancy (not enough studies to rule out risk).
• Breastfeeding:
  • Allopurinol passes into breast milk. If it’s necessary for a mother to take ZynolTab while breastfeeding, the infant should be monitored for any potential adverse effects.

Contraindications (CI):

• Hypersensitivity to Allopurinol:
  • Contraindicated in patients with a known allergy to allopurinol or any of its components.
• Acute Gout Attacks:
  • Allopurinol is not used to treat an acute gout attack. It is for chronic management and prevention of gout flares.
• Severe Renal or Liver Dysfunction:
  • Contraindicated in patients with severe renal failure or severe hepatic impairment, unless carefully monitored.
• Pregnancy (First Trimester):
  • Use with caution during pregnancy, especially in the first trimester. Category C drug.
• Allergic Reactions:
  • Discontinue the medication if there are signs of severe allergic reactions, such as skin rashes, difficulty breathing, or severe swelling.

Pharmacist Related Data

Chemical Formula:

• Allopurinol: C5H4N4O

Half-Life:

• Allopurinol has an elimination half-life of approximately 1 to 2 hours.
• Oxypurinol, the active metabolite of allopurinol, has a half-life of 15 to 30 hours. This prolonged half-life allows oxypurinol to maintain its uric acid-lowering effects for a longer period.

Metabolism:

• Allopurinol is metabolized primarily in the liver by xanthine oxidase (which it inhibits) to form oxypurinol, the active metabolite that exerts the majority of the therapeutic effect.
• Oxypurinol is also responsible for lowering uric acid levels.
• Both allopurinol and oxypurinol are excreted via the kidneys. Because of this, dose adjustments may be required for patients with renal insufficiency to avoid accumulation and toxicity.

Drug Interactions:

1. With Other Medications:
   • Azathioprine and Mercaptopurine: Both of these drugs are metabolized by xanthine oxidase, and since allopurinol inhibits this enzyme, it can lead to increased concentrations of azathioprine and mercaptopurine, which can cause bone marrow suppression and other serious side effects.
   • Warfarin: Allopurinol may increase the anticoagulant effect of warfarin, leading to an increased risk of bleeding.
   • Cyclophosphamide: Combining allopurinol with cyclophosphamide increases the risk of toxicity.
   • Thiazide diuretics: The use of diuretics (e.g., thiazides) with allopurinol may increase the risk of hypersensitivity reactions to allopurinol.
   • Rifampin and Phenytoin: These drugs may alter the metabolism of allopurinol, potentially reducing its efficacy.
2. With Food:
   • Food does not significantly affect the absorption of allopurinol. However, it is often recommended to take the drug after meals to reduce gastrointestinal upset.
   • Alcohol should be avoided or minimized as it can exacerbate the symptoms of gout and interfere with the efficacy of allopurinol in lowering uric acid levels.
3. With Other Gout Medications:
   • Colchicine or NSAIDs may be used alongside allopurinol to manage acute gout attacks. Care should be taken to avoid excessive gastrointestinal side effects, particularly when combining allopurinol with colchicine.

Pharmacodynamics:

• Mechanism of Action (MOA):
  • Allopurinol inhibits xanthine oxidase, an enzyme responsible for converting purines (from dietary sources and the breakdown of cells) to uric acid.
  • By inhibiting this enzyme, allopurinol lowers serum uric acid levels, reducing the risk of uric acid crystal formation in joints (which causes gout) and in the kidneys (leading to uric acid stones).
• Therapeutic Effects:
  • Prevents gout flares and reduces joint damage in patients with chronic gout.
  • Decreases uric acid levels, which helps prevent the formation of uric acid kidney stones.
  • Used in hyperuricemia (high uric acid levels), particularly in patients undergoing chemotherapy or radiation therapy.

Pharmacokinetics:

1. Absorption:
   • Allopurinol is well absorbed from the gastrointestinal tract after oral administration. It is generally taken once daily.
   • Peak plasma concentrations occur within 1-2 hours of taking the drug.
2. Distribution:
   • Allopurinol is moderately bound to plasma proteins (about 20-30%).
   • It is widely distributed throughout the body, including the central nervous system and kidneys, and can cross the placenta.
3. Metabolism:
   • In the liver, allopurinol is metabolized to oxypurinol by the enzyme xanthine oxidase (the same enzyme that it inhibits). Oxypurinol is the active metabolite responsible for most of the therapeutic effect.
   • The drug is not extensively metabolized to other significant metabolites, and oxypurinol has a longer half-life than allopurinol itself.
4. Excretion:
   • Both allopurinol and oxypurinol are primarily excreted by the kidneys.
   • In patients with impaired renal function, the clearance of both allopurinol and oxypurinol can be reduced, which may lead to drug accumulation and increased risk of toxicity.
   • Therefore, dose adjustments are necessary in patients with renal insufficiency (especially those with creatinine clearance below 30 mL/min).