Uricostatics

Uricostats - along with uricosurics and uricolytics (Dellas 2017) - are among the medications used in the context of chronic gout disease (Beubler 2011).

Uricosteroids include:

• 1. allopurinol

Half-life is 3 h, elimination is renal, therapeutic effect starts after 48 h and reaches maximum after 1 week (Oberdisse 2002).

• 2. febuxostat

The half-life is 5 - 8 h, elimination occurs primarily via the liver and only 1% - 6% via the kidney. Dose adjustment in renal insufficiency is not required (Rieke 2016).

(Beubler 2011)

Mode of action

Uricosteroids cause inhibition of xanthine oxidase, which oxidizes hypoxanthine to uric acid via xanthine (Beubler 2011).

The more water-soluble metabolites hypoxanthine and xanthine are then increasingly excreted in the urine, causing uric acid levels to fall (Dellas 2017).

Allopurinol also inhibits the de novo synthesis of purine bases from phosphoribosyl pyrophosphate (PRPP), which results in increased use of the salvage pathway and thus an additional reduction in uric acid levels (Dellas 2017).

Under treatment with uricolytics, good hydration is required to improve uric acid excretion (Dellas 2017).

Allopurinol can prevent the progression of gout. The target value of uric acid is between 5.0 - 6.0 mg / dl or 297 - 357 µmol / l (Herold 2021).

Indications

Allopurinol can be used for:

• Interval treatment in chronic hyperuricemia (1st choice agent).
• Prophylaxis during chemotherapy (cell decay leads to hyperuricemia).

Since most experience is available with allopurinol, this drug is normally preferred.

Febuxostat is only indicated when urate deposits are already present (Dellas 2017). It was approved for the therapy of tumor lysis syndrome in 2015 (Rieke 2016).

Contraindications

Allopurinol:

• Acute gout attack (Dellas 2017).
• Pregnancy
• Lactation

(Herold 2021)

Febuxostat:

• known CHD
• decompensated heart failure

(Herold 2021)

Side effects

Possible side effects are:

• Allopurinol may trigger a gout attack at the beginning of treatment. For this reason, gradual dosing is recommended (Dellas 2017).
• allergic skin reactions
• gastrointestinal disturbances
• Febuxostat generally causes fewer side effects

(Beubler 2011)

• nephrotoxic effect
• Stevens-Johnson syndrome (rare)

(Dellas 2017)

• Dry mouth
• Hair loss
• Fever
• Lyell syndrome
• Increase in transaminases

(Oberdisse 2002)

• Allopurinol hypersensitivity syndrome (allopurinol vasculitis) in 0.4 % of the cases

(Herold 2021)

With allopurinol, the frequency of side effects can be classified as low at 2 % - 3 % (Oberdisse 2002).

• V. a. an increased cardiovascular risk under treatment with febuxostat (Herold 2021)

Combination

It is possible to combine uricostats with:

• NSAIDS
• Colchicine

(Beubler 2011)

Interactions

Since allopurinol inhibits liver metabolism, an increase in effect may occur with:

• Coumarins
• Theophylline
• Azathioprine
• 6- mercaptopurine
• allergic skin reactions are possible with simultaneous administration of amoxicillin or ampicillin
• cytostatic treatment may increase blood count changes
• the excretion of probenecid is inhibited by allopurinol
• the main metabolite of allopurinol (oxipurinol) is excreted at an accelerated rate by benzbromarone

(Dellas 2017)

• there is a risk of leukocytopenia with concomitant treatment with captopril (Herold 2021)

Pregnancy and lactation

Uricostats should be avoided during both pregnancy and lactation. (Beubler 2011)

Contraindications

• Allopurinol:

Caution should be exercised in renal insufficiency (Beubler 2011). The dose should then be adjusted accordingly because of the risk of accumulation (Dellas 2017).

Since allopurinol is also metabolized hepatically, dose adjustment is also indicated in the presence of hepatic insufficiency because of the risk of accumulation (Dellas 2017).

Dosage recommendation

• Allopurinol:

When therapy is initiated, there is a risk of an acute gout attack, as the renal transport system is initially overwhelmed in most cases by the additional excretion of metabolites. Therefore, a gradual dosage is recommended at the beginning (Dellas 2017).

Herold (2021) recommends an initial dose of 100 mg / d with gradual increase over 1 month. The target dose is between 100 - 300 mg / d (Herold 2021).

Alternatively, colchicine 2 x 0.5 mg / d can also be given for about 6 months for the prophylaxis of a gout attack (Herold 2021). Another option is parallel treatment for 3 months with NSAIDs (Dellas 2017).

• Febuxostat:

80 mg / d (Herold 2021)

1. Beubler E (2011) Compendium of pharmacology: common drugs in practice. Springer Verlag Vienna 118
2. Dellas C (2017) Short textbook pharmacology. Elsevier Urban and Fischer Publishers 191 - 192.
3. Herold G et al (2021) Internal medicine. Herold Publishers 707 - 708
4. Oberdisse E et al (2002) Pharmacology and toxicology. Springer Verlag 549
5. Rieke H et al (2016) Gout: the current state of knowledge on etiology, pathogenesis, diagnosis, clinic and therapy. De Gruyter Publishers 7.5