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Overview

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Name

Allopurinol

Precaution

Allopurinol is a medication primarily used to manage **gout** and **hyperuricemia** (elevated levels of uric acid in the blood). While effective, it requires caution in certain populations: - **Pregnancy and Breastfeeding**: Allopurinol is classified as a Category C drug during pregnancy, meaning it should be used only if the potential benefit outweighs the potential risk to the fetus. There is limited data on its safety during pregnancy. Allopurinol is excreted in breast milk, and while adverse effects on nursing infants are rare, it is recommended to avoid breastfeeding or use the drug cautiously in lactating women. - **Renal Impairment**: Allopurinol should be used with caution in patients with renal impairment. Dosing adjustments are often necessary, as impaired renal function can lead to an accumulation of the drug, increasing the risk of side effects. In patients with severe renal insufficiency, the dose should be reduced, and renal function should be closely monitored. - **Hepatic Impairment**: In patients with hepatic disease, allopurinol should be used with caution, and monitoring liver enzymes may be required, as liver dysfunction can affect the drug’s metabolism and excretion. - **G6PD Deficiency**: Allopurinol should be used cautiously in patients with **glucose-6-phosphate dehydrogenase (G6PD) deficiency**, as this condition increases the risk of hemolytic anemia when treated with allopurinol. - **Drug Hypersensitivity**: Hypersensitivity reactions, including rash, fever, and more severe conditions like **Stevens-Johnson syndrome (SJS)** or **toxic epidermal necrolysis (TEN)**, have been associated with allopurinol. These reactions are more likely to occur within the first few weeks of therapy, so any signs of an allergic reaction (skin rash, fever, or flu-like symptoms) should be reported immediately. **Monitoring Parameters**: - **Renal Function**: Serum creatinine and urine output should be monitored regularly, especially in patients with pre-existing renal conditions. - **Liver Enzymes**: Liver function tests (ALT, AST) should be monitored, particularly in patients with hepatic impairment. - **Uric Acid Levels**: Serum uric acid levels should be periodically checked to evaluate the effectiveness of treatment and ensure that they are within the target range.

Indication

Allopurinol is primarily indicated for the treatment of **gout** and **hyperuricemia**, where it helps lower uric acid levels in the blood, thus preventing the formation of uric acid crystals in the joints and reducing the occurrence of gout flares. It is also used to prevent **uric acid nephropathy** in patients undergoing chemotherapy, as chemotherapy can lead to tumor lysis syndrome, causing high levels of uric acid to be released into the bloodstream. Allopurinol is also indicated for managing **secondary hyperuricemia** associated with other conditions such as **renal failure** and **psoriasis**, where excess uric acid levels may cause complications. In certain cases, allopurinol is used off-label in the treatment of **calcium oxalate nephrolithiasis** (kidney stones).

Contra indication

Allopurinol is contraindicated in the following conditions: - **Hypersensitivity to Allopurinol**: Patients with a known allergy to allopurinol or any of its components should avoid its use. - **Severe Renal Impairment**: In patients with severe renal insufficiency, allopurinol is contraindicated, as its accumulation can lead to toxicity. - **Acute Gout Attacks**: While allopurinol is used to prevent gout attacks, it should not be used during an acute gout flare, as it can exacerbate the inflammation. Instead, other medications (e.g., NSAIDs, colchicine) should be used to manage the acute attack.

Side Effect

The side effects of allopurinol range from mild to severe and are dose-dependent: - **Common Side Effects**: - **Rash**: A mild skin rash is a common side effect, which may resolve with continued therapy. - **Gastrointestinal Issues**: Nausea, vomiting, and diarrhea may occur, particularly when first starting the medication. - **Headache**: Some patients report headaches during treatment. - **Serious Side Effects**: - **Severe Hypersensitivity Reactions**: Allopurinol can cause severe allergic reactions, such as **Stevens-Johnson syndrome** (SJS) and **toxic epidermal necrolysis** (TEN), which are life-threatening conditions involving widespread skin rashes, blisters, and systemic symptoms. Discontinuation of the medication is required if these reactions occur. - **Hepatitis**: Liver damage, indicated by jaundice, elevated liver enzymes, and abdominal pain, can occur. - **Aplastic Anemia**: Although rare, bone marrow suppression leading to anemia, leukopenia, and thrombocytopenia has been reported. - **Renal Toxicity**: Prolonged use of allopurinol in patients with pre-existing renal impairment can lead to nephropathy, especially if dosing adjustments are not made. Patients experiencing any severe reactions (e.g., skin rash, fever, sore throat, or bruising) should seek immediate medical attention. To minimize side effects, it is essential to start with a low dose and gradually increase it.

Pregnancy Category ID

3

Mode of Action

Allopurinol works by inhibiting **xanthine oxidase**, an enzyme responsible for the conversion of hypoxanthine to xanthine and xanthine to uric acid. By inhibiting this enzyme, allopurinol reduces the production of uric acid, which is a key factor in the formation of urate crystals in joints (causing gout) and the kidneys (leading to kidney stones). The reduction in uric acid levels helps prevent gout attacks, alleviate symptoms of gout, and prevent uric acid nephropathy in patients undergoing chemotherapy. By lowering uric acid levels, allopurinol helps decrease the frequency and severity of gout attacks over time.

Interaction

Allopurinol can interact with various medications, affecting their efficacy or increasing the risk of side effects: - **Azathioprine and Mercaptopurine**: Allopurinol inhibits the enzyme **xanthine oxidase**, which is responsible for the metabolism of azathioprine and mercaptopurine. This can lead to increased levels of these immunosuppressive drugs, increasing the risk of toxicity, including bone marrow suppression. Dosing adjustments for these medications are necessary when used together. - **Warfarin**: Allopurinol can enhance the anticoagulant effects of warfarin, increasing the risk of bleeding. Close monitoring of INR (International Normalized Ratio) is recommended when starting or adjusting doses of allopurinol in patients taking warfarin. - **Diuretics**: The use of thiazide diuretics, such as hydrochlorothiazide, can increase the risk of allopurinol-induced toxicity, especially in patients with renal impairment. Thiazide diuretics can also increase uric acid levels, which may counteract the effect of allopurinol. - **Antacids**: Antacids containing aluminum hydroxide can reduce the absorption of allopurinol and should be used with caution or spaced apart from allopurinol doses. **Food and Alcohol**: - **Food**: Allopurinol can be taken with or without food. However, it is often recommended to take it with food to minimize gastrointestinal upset. - **Alcohol**: Alcohol can increase uric acid levels and may counteract the effect of allopurinol. While moderate alcohol consumption might not be contraindicated, excessive alcohol intake should be avoided during allopurinol therapy due to the risk of precipitating a gout attack or reducing the effectiveness of the medication.

Pregnancy Category Note

Information not available

Adult Dose

For the treatment of **gout** and **hyperuricemia**, the typical starting dose of allopurinol is **100 mg per day**, which may be gradually increased based on the patient's response and uric acid levels. The usual maintenance dose is **200 to 300 mg per day**, but in some cases, higher doses (up to 800 mg per day) may be required for more severe conditions. In patients with renal impairment, dosing should be reduced to avoid drug accumulation and toxicity. For **secondary hyperuricemia** related to chemotherapy, the initial dose is usually **300 mg per day**, which may be adjusted based on uric acid levels.

Child Dose

Allopurinol is generally not recommended for use in children under 6 years old. For children over 6 years, the dose typically starts at **100 mg/day**, which can be increased based on weight and uric acid levels. Dosing adjustments may be required in children with renal or hepatic impairment.

Renal Dose

In patients with **renal impairment**, dosing adjustments are necessary due to reduced clearance of allopurinol. The dose is typically reduced based on the patient's creatinine clearance: - **CrCl 10-20 mL/min**: Start with 100 mg/day, with adjustments based on response. - **CrCl <10 mL/min**: Start with 50 mg/day and titrate as needed, with close monitoring.

Administration

Information not available