Alopurinol

Summary

Allopurinol is a molecule that reduces the body’s production of uric acid (hypouricemic), the drug is indicated in cases of gout and symptomatic hyperuricemia.
This molecule has a preventive action and is useful in cases of gout (once triggered). Allopurinol is contraindicated in asymptomatic hyperuricemia, that is, when uric acid levels (blood) are high, but there are no symptoms (no gout, no pain, etc.).

About a molecule

Chemical name: 1,5-diidro-4H-pyrazol[3,4-d]-pyrimidin-4-one, C 5 H 4 N 4 O
Molecule names:  allopurinol, allopurinol, Allopurinolum PhEur Trade
names:   Allopurinol, Zyloric

Dose

– Minimum: 100 mg/day

– Maximum: 800 mg/day, note that the maximum daily dose may vary according to each country (different laws). In Brazil, the usual dose for preventing gout is 100 to 300mg/day, but the maximum dose can reach 800mg/day. In France, the maximum dose is 300mg/day, while in Switzerland some scientific sources (Etzel Gysling “Hundert wichtige Medikamente, 2005) recommend up to 600mg/day.

Note: Doses greater than 300 mg/day should be administered divided (fractionated) throughout the day.

According to the recommendations of the French Agency for the Safety of Medicines (ANSM) published at the beginning of 2013, it is still recommended to gradually increase the dose of allopurinol and adapt it according to uric acid (which must be measured regularly ). This helps to reduce the occurrence of adverse effects, some very serious, especially on the skin (see below under adverse effects).

Allopurinol metabolism
The maximum concentration of allopurinol is reached 1-2 hours after the dose, the molecule has a half-life of 1 hour, the half-life time characterizes the time required to reach half the concentration of the molecule. However, allopurinol is broken down in the body primarily to a metabolite called oxypurinol, which acts like allopurinol. Oxypurinol has a half-life of 18 to 30 hours. During regular intake of allopurinol, the main effect in preventing gout is achieved by oxypurinol.

Class
Allopurinol belongs to the class of xanthine oxidase inhibitors. Another molecule of this class is febuxostat, a molecule indicated in the prevention of gout attacks.

Posology

Adult and geriatric use (note that dosages may vary from one country to another, purely informative indications)

– Moderate gout: 200 to 300 mg/day (also read Dose)

– Severe gout (dosage proposed in some countries): 400 to 600 mg/day

In France, the usual maximum dose seems to be 300 mg per day, in Switzerland (read Dose) doctors can prescribe up to 600 mg per day (in 24 hours). In Brazil, there are medical protocols that indicate doses of up to 800mg/day, for very severe cases.

– Hyperuremia associated with chemotherapy: 600 to 800 mg/day, divided into 2 or 3 doses

– Other indications: Start with 100 mg/day and gradually increase the dose every 4 weeks, monitoring the plasma uric acid level.

Pediatric use (note that dosages may vary from one country to another, for purely informative indications)

Note: Some sources believe that the use of allopurinol in children is not highly recommended (risk of adverse effects), for the daily dose of allopurinol a dose of 10 to 20 mg per kg per day is possible.

Below are listed some dosage indications (attention, always ask your doctor or pharmacist).

– Children < 6 years: 150 mg/day

– Children between 6 and 10 years old: 300 mg/day

– Children over 10 years old: adult dose

Comments:

– People with renal insufficiency (especially the elderly) require a dose adjustment according to the degree and progression of the disease.

– It is advisable to measure serum uric acid and uremia regularly.

Indications

– Gout attacks (may take 6 weeks to get full effect)

The objective of allopurinol-based treatment in the prevention of gout is to reduce uric acid levels to 6mg/dL (0.36 mmol/L). If this objective is not achieved, the physician may increase the dose.

– Elevated levels of uric acid during chemotherapy or radiotherapy (for example, for leukemia or lymphoma)

– Kidney problems caused by gout

– Pedra no rime

– Avoid adverse effects due to fluorouracil

Attention: It is not recommended in acute gout attacks when the person is not yet using this medication, as in this case the risk of new gouty attacks increases.

Effects

It reduces the production of uric acid in our body, particularly in plasma and urine, acting as a hypouricemic agent.

Allopurinol is an inhibitor of xanthine oxidase (enzyme), the latter acts on the metabolism of uric acid in the transformation (oxidation) of hypoxanthine into xanthine and then into uric acid. If xanthine oxidase is blocked, there is an automatic reduction in uric acid production.

You should know that allopurinol produces a metabolite called oxypurinol, which also has an action like uric acid on xanthine oxidase. Oxypurinol has a longer duration of action than allopurinol and has a superior hypouricemic effect. The elimination of oxypurinol is essentially renal.

Adverse effects

Note
To reduce the risk of side effects, allopurinol is contraindicated in cases of asymptomatic hyperuricemia, ie when uric acid (blood) levels are high but there are no symptoms (no gout, no pain, etc).

Main adverse effects:
– Skin irritation (urticaria, etc.), these adverse effects occur in 5 to 10% of cases. Much more rarely, more severe cutaneous reactions (“rash”) such as hypersensitivity syndrome (allergy) such as Lyell syndrome, Stevens-Johnson syndrome and DRESS. with eosinophilia and systemic symptoms. These severe rashes seem to have a female predominance. You should be aware that these adverse effects usually occur within 2 months of starting treatment. In cases of symptoms such as fever, rash, hypersensitivity or other symptoms that have nothing to do with the gout, stop treatment immediately. Consult your doctor or pharmacist for more information.

Pharmacogenetics
Persons carrying the HLA-B*5801 allele are at increased risk of developing Stevens-Johnson syndrome and Lyell syndrome (also called Toxic Epidermal Necrolysis), as a side effect of using allopurinol and other hypouricemic drugs. These two syndromes can lead to death. It is known that Asians and blacks carry this allele more frequently than whites or Latinos, as shown by an American research published in April 2016.

– Gastrointestinal problems (diarrhoea, vomiting, nausea).

– Liver problems, rare adverse effect.

– Attack of gout (sometimes it can trigger an attack, at the beginning of the treatment)

– Increased liver enzymes

With the purchase of a medicine, read the leaflet.

contraindications

People who are allergic to allopurinol or any of its components. Acute gout attack. Renal insufficiency (especially in severe cases), in this case the doctor or pharmacist should reduce the dose according to the renal clearance. Liver failure (reduce dose).

With the purchase of a medicine, read the leaflet.

Drug interactions

Major interaction – evaluate medication switching

– ACE inhibitor drugs (increases the risk of hypersensitivity).

– Antacids (may decrease the absorption of allopurinol). With the exception of baking soda.

– Mercaptopurine (may decrease the metabolism of this medicine).

– Warfarin or didanosine (may increase the concentration of these drugs).

Moderate interaction – monitor

– Amoxicillin and ampicillin (increases the risk of rashes).

– Anticonvulsants, carbamazepine, chlorpropamide (may increase the concentration of these medicines).

– Loop diuretics such as furosemide (may increase adverse/toxic effects of allopurinol).

– Derivatives of theophylline.

– Thiazide diuretics such as hydrochlorothiazide (increases the risk of hypersensitivity and allopurinol concentration).

Pregnancy and lactation

There are not enough animal or human studies regarding the use of allopurinol in pregnant women, so the risk during pregnancy cannot be measured. It should be used in pregnant women only if the benefits outweigh the risks to the fetus (when the disease itself poses a risk to the life of the mother or fetus), consult a physician for this assessment.

Nursing mothers should use with caution. Allopurinol is excreted in milk, but its effect on the baby is not known.

pharmaceutical presentations

– Pills 100 or 300 mg

Tips

To get the best effect from Allopurinol:

– Take it preferably after meals and swallow the tablets whole with a full glass of water.

– Consume plenty of decaffeinated liquid, unless your doctor recommends consuming less liquid.

– Continue taking this medication even during the gout attack.

– Report to the doctor all the medicines you are taking (including medicines, medicinal plants, vitamins, natural products, among others), to reduce the risk of interactions.

– Tell your doctor if you are pregnant, breastfeeding or have kidney and liver problems.

– Do not take antacids within 6 hours of this medicine (before or after).

– Do not consume alcohol or in some cases with limitations (ask your doctor or pharmacist).

– If you miss a dose, take the missed dose as soon as possible. If it is close to your next dose, skip the missed dose and take your next dose at your regular time.

– Do not use 2 doses or extra doses.

– Allopurinol can, in rare cases, lead to serious adverse effects such as toxidermia – skin rash (sometimes fatal reaction affecting the skin). In cases of symptoms such as fever, rash, hypersensitivity or other symptoms that have nothing to do with gout, stop treatment immediately . Consult your doctor or pharmacist for more information.

These adverse effects usually occur within 2 months of starting treatment. Also read on adverse effects and read the package insert when purchasing any medication.

– You should know that after administration, uric acid decreases within 24 to 48 hours and daily intake of allopurinol leads to a maximum drop in uric acid after about two weeks. With interruption of treatment, uric acid tends to return to its previous value after 7 to 10 days, so it is important to continue treatment without interruption.

This is a long-term treatment.

Interestingly, many people take this allopurinol-based treatment for the first year and stop for the second year. This procedure is dangerous because it poses a risk to the patient’s health (gout crisis, kidney complications, etc.). Ideally, you should take the medicine every day, your pharmacist can help you achieve this.

– At the beginning of therapy with allopurinol, attacks of gout may occur (paradoxical effect, since the purpose of treatment is precisely to reduce crises).

– After starting the use of allopurinol for gout prevention, it is important to have at least one blood test for uric acid, in order to verify the effectiveness of the treatment.

– The use of allopurinol in the prevention of gout is usually a lifelong treatment.

– Allopurinol was authorized by the FDA (United States drug regulatory agency) in 1966.

– Allopurinol is on the WHO list of essential medicines (updated April 2013).

Also read our full file on gout

legal note

The information contained and published on this page is merely informative, it does not replace the advice of the doctor or pharmacist. For more information, when purchasing a medication, read the leaflet.

Source:
Etzel Gysling “Hundert wichtige Medikamente 2005, French Medicines Safety Agency (ANSM)

Jeanne Kenney
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I’m a stylist trainer, a content creator, and an entrepreneur passion. Virgo sign and Pisces ascendant, I move easily between my dreams, the crazy world I want, and my feet on the ground to carry out my projects.

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