The drug "Allopurinol": analogues worthy of attention and reviews about them

Allopurinol is a drug that effectively reduces the concentration of uric acid. As a result, its deposition in the bladder, kidneys, and joints is prevented. Urolithiasis is one of the most well-known ailments. Stones in the kidneys and bladder are of different natures, so the treatment regimen is selected individually.

The medication prevents the increase and deposition of urate. The instructions for the drug "Allopurinol" indicate that it can disrupt the mechanism of uric acid formation. The drug inhibits the activity of xanthine oxidase.

For what diseases is it prescribed?

The drug "Allopurinol" is prescribed for:

• gout;
• kidney stone disease;
• lymphosarcoma, acute leukemia,
• chronic myeloid leukemia;
• traumatic injuries;
• cytostatic and radiation therapy;
• Lesch-Nien syndrome;
• massive glucocorticoid therapy;
• uric acid nephropathy.

At the beginning of the course, a minimum dose of 100 mg is prescribed in order to identify side effects and possible complications of the Allopurinol drug. If there are no negative reactions, then the dosage of the drug is calculated based on uric acid in the blood. After which it is increased stepwise by 100 mg.

Indications for use

The medicine is intended for use in the following cases:

1. Treatment or prevention of gout and hyperurmemia of various origins is carried out.
2. There is an exacerbation of calcium oxalate stones in the kidneys.
3. The formation of urates increases due to enzymatic abnormalities.
4. Acute nephropathy is prevented during the period of cytostatic and radiation treatment of neoplasms and leukemia or during complete fasting of a therapeutic nature.

Side effects

The drug "Allopurinol" has side effects:

• anemia, agranulocytosis, leukocytosis, thrombocytopenia;
• increased blood pressure, bradycardia, pericarditis;
• acute renal failure, proteinuria, decreased potency, peripheral edema;
• decreased vision, loss or distortion of taste, amblyopia;
• nausea, vomiting, diarrhea, cholestatic jaundice;
• neuropathy, headache, drowsiness, depression;
• allergic reactions.

"Allopurinol." Analogues

The drug "Allopurinol" has more than 14 analogues. This means that patients to whom a doctor has prescribed this drug have the right to choose. The main indications for taking all the drugs listed below include not only the treatment of gout, but also excessive accumulation of uric acid in the blood (hyperuricemia) of various origins.

Indications also include a combination of gout with urate nephropathy, renal failure, and nephrolithiasis. Another indication is increased urate formation due to the presence of enzyme disorders. In addition to therapy, this drug can also be used to prevent nephropathy during treatment of cancer, as well as complete therapeutic fasting.

Each form has its own side effects, which are not too many and their manifestations are quite rare, but you need to know about them. For example, the most common: increased fatigue, diarrhea, weakness, baldness, blood disorders. This is confirmed by the instructions for the drug "Allopurinol".

Allopurinol analogs

Many people are interested in whether it is possible to replace Allopurinol with something when being treated for gout? Yes, there are similar medications, they differ in price and ingredients, but the basis of each is still allopurinol. Let's look at some of them:

Purinol

Tablets that affect the metabolism of uric acid. Used in the treatment of gout. While using this drug, the patient should consume at least two liters of fluid daily.

At the initial stage of therapy, there is a possibility of exacerbation of the disease, so experts advise taking anti-inflammatory compounds at this time.

When using Purinol, there is a possibility of large stones dissolving in the bladder with their further release into urine.

The dosage is prescribed individually, the drug is dispensed at the pharmacy upon presentation of a prescription.

Allopurinol – EGIS

It is the leader among all the drugs that reduce the level of uric acids in the blood. Allopurinol - EGIS is used for idiopathic gout, urolithiasis, acute nephropathy, and neoplasms.

During the first month of the therapeutic course, it is necessary to take NSAIDs or colchicine to prevent acute attacks of gout. Elderly patients and those suffering from kidney failure need to adjust the dosage to avoid intoxication.

Allozyme

Used for primary and secondary gout, urolithiasis when uric acid stones are formed, diseases during which there is an increased breakdown of nucleoproteins, radiation and cytostatic treatment of neoplasms, psoriasis, traumatic toxicosis.

Allopurinol Nycomed

The medicine refers to drugs that can prevent the appearance of stones in the bladder and accelerate their elimination along with biological fluid. Almost completely absorbed from the gastrointestinal tract. The maximum value in the blood is one and a half hours after administration.

Allopurinol-Teva

Used in the treatment of gout, malignant tumors and abnormalities in purine metabolism in children, traumatic toxicosis, psoriasis. The tablet is taken orally, after meals, with a sufficient amount of water. It is allowed to distribute the daily dose into several parts.

Zilorik

The tablets lower the level of urate in the total amount of water in the body and in biological fluid, and prevent acid deposition.

Not recommended for use by patients suffering from individual intolerance to the components of the drug. Side effects are rare.

Sanfipurol

A drug that affects the metabolism of uric acid. Used for gout, stones in a paired organ, acute nephropathy, therapeutic treatment of tumors or leukemia. The dose is taken once a day after meals. During the treatment course, it is recommended to consume at least two liters of fluid daily.

Milurite

An anti-gout medicine that inhibits the synthesis of lactic acid and salt accumulations in the body. The urate content in blood cells is reduced, and their deposition in tissues and paired organs is prevented. When taking this drug with urine, a smaller amount of uric acids is released, and the level of excreted xanthine and hypoxanthine increases.

Remid

The tablets are taken orally after meals. The daily dosage can be divided into two doses. To reduce the risk of gout exacerbation, therapy should be started with small doses.

Allopin

The active ingredient is allopurinol.

The tablets create a hypouricemic and anti-gout effect, inhibit xanthine oxidase, disrupt the conversion of hypoxanthine to xanthine and then to uric acids.

Under the influence of this medicine, the level of urates in the blood is reduced and their accumulation in the body is prevented. Absorption occurs in the stomach and intestines.

"Hello"

One of the most popular and well-known analogues is “Allo”, which has the same active ingredient as “Allopurinol”, and therefore can rightfully be considered a complete substitute. Dosage depends on the condition of the patient. For example, if the symptoms are mild, 200-300 mg per day should be taken orally, and if the symptoms are pronounced, then 400-600 mg per day. Tablets are taken 2 times a day after or during meals, for example, immediately after breakfast. Other data, including side effects, contraindications and indications, fully correspond to the original drug.

What other analogues of the drug “Allopurinol” exist?

Analogues in composition

Gout or gouty arthritis is a metabolic disease in the human body that affects the metabolic processes of uric acid derivatives, which ultimately provokes increased deposition of uric acid salts in the tissues of the body. It is because of these deposits that malfunctions in the functioning of some organs and tissues occur in a short time.

Most often, joints, kidneys and other organs are affected. If no measures are taken, serious problems may occur. It is no longer possible to cure the disease completely, but stable remission can be achieved, the main thing is to seek qualified help and take effective medications, such as Allopurinol or its analogues.

Purinol

Allopurinol, analogs and substitutes of which include Purinol, is a drug actively used in urology and is often recommended for patients with a diagnosis such as gout. Both drugs have an identical active component, which has the special ability to inhibit the formation of uric acid. After taking both drugs, the concentration of uric acid in the blood decreases significantly, due to which urate stones are actively dissolved.

Purinol is a complete analogue and substitute for Allopurinol

Both drugs are indicated for:

• psoriasis;
• gout;
• enzyme disorders;
• other serious pathologies.

The contraindications for both drugs are similar, and Purinol has much more undesirable manifestations. The price of the drugs is identical.

Hello

Allopurinol (analogs and substitutes are described in this article) and Allo are 2 drugs that have an identical active ingredient. The dosage of the substitute is selected individually in each individual case, because everything depends on the patient’s health condition and the complexity of the disease. So, for example, if the symptoms are mild, then it will be enough to take 200-300 mg of the drug per day, but if the symptoms are pronounced, the dosage can be doubled.

Undesirable manifestations, contraindications and indications for use of the 2 drugs are identical. The only difference between them is the price: Allo’s is slightly higher.

Allupol

Allopurinol (analogs and substitutes) and the drug Allupol are 2 identical medications that help in the treatment of gout. Both drugs have the same active ingredient. But before making a replacement, it is better to consult a specialist.

As indicated in the instructions, for both drugs the minimum dosage is 200 mg per day, and the maximum is no more than 900 mg. In no case should you exceed the prescribed dosage on your own, even if the symptoms do not go away. Increasing the dosage can lead to serious complications.

There are differences between the 2 drugs, for example, Allupol should not be taken by people who have problems with the functioning of the kidneys and liver. While taking Allupol, it is necessary to monitor the functioning of internal organs. The price of both drugs differs little.

Milurite

When choosing an analogue of Allopurinol, you should pay attention to a drug such as Milurit. Both drugs have an identical active substance that helps inhibit the formation of uric acid. It is allopurinol and its main metabolite oxypurinol that has the unique property of disrupting the synthesis of uric acid.

As a result of taking the drugs, the concentration of uric acid in the blood decreases and urate stones dissolve. Both drugs have similar indications, contraindications, as well as undesirable manifestations in case of non-compliance with the established rules of administration. Their prices are identical.

Sanfipurol

This is another effective anti-gout drug, which is considered an ideal analogue of Allopurinol.

The drug contains an identical active substance, which has the ability to inhibit the formation of lactic acid. Allopurinol and its main metabolite, oxypurinol, have a unique property: they interfere with the synthesis of uric acid.

Both drugs contain 100 or 300 mg of the active ingredient. They should be taken twice a day, the dose is selected individually depending on the severity of the disease. Indications, contraindications and adverse events for both drugs are identical. The price is also not much different.

"Allupol"

"Allupol" is another analogue of "Allopurinol", also available in tablets and having the same international name and active substance. But before replacing one drug with another, you should consult a specialist. The minimum daily dose is 100-200 mg of the drug, and the maximum is 900 mg. It is not recommended to exceed the specified amount under any circumstances. The use of Allupol is contraindicated in patients with liver and kidney diseases. During the course of treatment, it is necessary to carefully monitor the functioning of these organs.

"Zilorik"

"Zilorik" is a generic, a foreign analogue of "Allopurinol". Its cost exceeds the price of domestic drugs several times, although the composition and indications for use are completely the same as the Russian drug. The initial dosage usually does not exceed 300 mg for mild disease, 600-800 mg is prescribed for severe disease. Elderly patients and people with kidney diseases should take the drug strictly individually according to the dosage prescribed by the doctor or replace it with a medicine based on a different active substance.

There are other analogues of the drug "Allopurinol".

"Milurit"

"Milurit" is a fairly popular foreign substitute for the original medicine, but it is quite difficult to find in pharmacies.

Analogues for the treatment of gout: “Sanfipurol”, “Allozyme”, “Remid”, “Allopin”, “Purinol”, “Allopurinol Nycomed”, “Apo-Allopurinol”, “Allopurinol-Teva”, “Allupol”, “Allopurinol-Egis” "

The cost of the drugs depends on the number of tablets in the package and the dosage, but on average it ranges from 65 to 150 rubles. One of the most purchased and frequently prescribed dosages is 100 mg. But for patients with a progressive disease or its severe form, purchasing the drug is unprofitable, since its dosage is too small, and to obtain the required amount of active substance (600-900 mg), you will need to immediately drink 6-9 tablets, and this is extremely inconvenient. Therefore, for patients requiring a higher dosage, drugs in an amount of 300 mg are recommended. However, while a 100 mg package contains 50 tablets, a 300 mg package contains only 30 tablets.

Let's name a few more analogues of Allopurinol.

The list of substitutes includes the well-known drug Allopurinol-Egis, produced in Hungary by the pharmaceutical company Egis. This manufacturer is considered a leader in the production of drugs for the treatment of gout.

A popular manufacturer of generic drugs is the pharmaceutical industry, which produces medicines that are no different in composition from the original ones.

Another world-famous manufacturer of generic drugs is , which produces cheap analogues of original drugs.

"Colchicine"

Drugs similar in action to Allopurinol and used as its substitute, but not its analogues, are presented below.

For modern medicine, Colchicine is one of the best drugs used to treat gout. Let's figure out what is better - Colchicine or Allopurinol?

Colchicine acts as an anesthetic, neutralizes the formation of salt deposits in tissues and minimizes the migration of leukocytes in the affected area. The medicine has a plant base, contains autumn colchicum as the main component, and therefore it can be used not only for treatment, but also for prevention.

Patients tolerate it quite well. The effectiveness of the medicine depends on correct administration. The maximum dosage should not be more than 10 tablets per day. The course of treatment is completed as prescribed by the doctor and after achieving the desired result. Colchicine should not be taken by patients with liver or kidney failure or hypersensitivity to any component of the drug. You should also take the drug with caution during pregnancy and only after consultation with a specialist. Side effects and overdose of the medicine can cause diarrhea and vomiting. If the patient experiences atypical side effects, you should immediately stop taking the drug and consult your doctor. The drug should not be taken for a long time, as this poses a risk of developing leukopenia and anemia.

"Fullflex"

Recently, “Fulflex” has become a fairly popular drug. It is produced in 2 forms - tablets and cream - which allows you to treat the disease both from the outside and from the inside. The medicine refers to drugs that have a short-term effect and have anti-inflammatory and analgesic effects. The medicine contains extracts of juniper and sage, fragrant martinia, essential oils of eucalyptus, willow bark, horse chestnut, birch bark, vitamins PP and E.

Analogues in action

While Allopurinol is suitable for some patients in the treatment of gout, others have a particular sensitivity to its active component. It is for such people that it is necessary to select an analogue with an identical effect, but containing a different substance as the main component.

Colchicine

Allopurinol (analogs and substitutes can be taken only after consultation with the attending physician) and Colchicine are available in identical form - in tablets. Also, 2 drugs are prescribed for gout, but this is where the similarity of their properties ends.

Colchicine contains a substance of the same name, which also has a direct effect on the metabolic processes of uric acid in the human body. The substance belongs to the alkaloids isolated from the corms of the splendid colchicum.

It is thanks to this component that the drug has a pronounced analgesic and anti-inflammatory effect. The tablets suppress the mitotic activity of granulocytes. They reduce the migration of leukocytes to the site of inflammation, inhibit the phagocytosis of uric acid, delaying its deposition in the tissues of internal organs.

Colchicine has a minimum of contraindications: special sensitivity, pregnancy and kidney and liver failure.

The number of undesirable manifestations is also minimal: vomiting, nausea, impaired renal function, and with long-term use, alopecia may occur. There is one more difference - the price; for Colchicine it is much higher.

Febuxtostat

Febuxtostat is another effective substitute for Allopurinol recommended for the treatment of gout. Comparing the 2 drugs, we can say that they are both available in tablet form and have suppressive properties on the formation of uric acid. Both drugs have identical contraindications. This is where their similarities end.

As for the differences, the first of them is the active substance. In Febuxtostat it is a component of the same name. The drug should be taken 1 time per day.

If the dosage is exceeded or the course is increased, the following undesirable symptoms may occur:

• attack of gout;
• liver dysfunction;
• nausea;
• headache;
• allergic reaction.

The price of the analogue is much higher, almost twice.

Azurix

This is another medicine that is prescribed for the treatment of gout. There are minimal similarities between the two drugs – Azurix and Allopurinol. One of them is the release form - tablets.

Azurix contains febuxtostat as an active component. It is thanks to this component that the drug is a derivative of 2-arylthiazole and is the strongest selective non-purine xanthine oxidase inhibitor. This enzyme catalyzes 2 stages of purine metabolism: the oxidation of hypoxanthine to xanthine, and then the oxidation of xanthine to uric acid.

It is due to the inhibition of xanthine oxidase that the concentration of uric acid in the blood decreases. If the drug is taken in a therapeutic dosage, it does not inhibit other enzymes that are actively involved in the metabolism of purines or pyrimidines.

According to reviews from patients and specialists who prescribe Azurix, the drug is effective in the treatment of gout, but has a lot of undesirable manifestations and contraindications. In addition, the drug has a significantly higher price than Allopurinol.

Fullflex

Currently, this medicine is particularly popular. This is what is prescribed to patients with gout if Allopurinol is not suitable for any reason. This drug is available in 2 forms: tablets and cream for external use, which allows you to treat the disease from the inside and outside. The drug belongs to the group of short-acting drugs and has analgesic and anti-inflammatory effects.

Comparing both drugs, we can say for sure that they have different components. Fullflex contains many natural ingredients and each of them has its own special effect on the human body. The active components and their properties are described in the table below.

The composition also includes other components that are no less useful for the musculoskeletal system.
Among them:

1. Juniper extract.
2. Sage.
3. Essential oils:

• eucalyptus,
• willow bark,
• horse chestnut,
• birch bark.

Both drugs have identical indications:

• rheumatism;
• gout;
• arthritis;
• myalgia.

Contraindications and undesirable manifestations are also similar. The price of Fullflex is a little more expensive.

Liquestia

This is another effective analogue of Allopurinol, which is no less effective in the treatment of gout, but is very different. If we compare the two drugs, they are similar in indications for use and identical in release form, but they have much more differences.

Liquestia has a completely different active component - febuxostat. There are other equally significant differences, for example, Liquestia has almost no contraindications for use, and undesirable manifestations are observed in very rare cases and then only when the patient tries to achieve a quick effect and independently increases the daily dosage. Liquestia also has another significant difference - its price is almost 7 times higher than Allopurinol.

Blémarin

This is another good and effective analogue that helps dissolve urinary deposits. The drug additionally increases the pH level of urinary fluid. The drug is available in the form of effervescent tablets, which are recommended to be dissolved in a glass of water or a cup of tea before use. The effervescent pills contain three active ingredients: potassium bicarbonate, citric acid and sodium citrate.

It is thanks to this composition that the drug dissolves and subsequently prevents the formation of uric acid stones, all due to the alkalization of urine. The product also reduces calcium excretion, improves the solubility of calcium oxalate in urine, inhibits the formation of crystals, and therefore prevents the appearance of calcium oxalate stones.

The two drugs have quite a few similarities - these are indications for use, and everything else is very different. It is for this reason that before you start taking the drug, it is better to consult a specialist.

Allopurinol is an effective, inexpensive anti-gout drug that, when taken correctly, helps send gout into stable and long-term remission. The drug is effective, but some people have special sensitivity to its main component or additional components, which is why they have to look for an equally effective analogue or substitute.

Only a specialist should select the drug, because many analogues have their own contraindications and undesirable manifestations, and in order not to provoke the development of complications, you need to know about them before starting to take the drug.

Other substitutes

Attacks of gouty arthritis can be temporarily stopped with the help of Voltaren. Taking tablets and ointment simultaneously helps achieve maximum effect. On the first day, the drug is taken at a dosage of 200 mg, and then 150 mg per day, and the ointment is rubbed on the sore joint 2 times a day.

Diclofenac and ibuprofen have a similar effect, reducing fever, relieving pain, swelling and inflammation. The same dosage regimen is used for Naproxen. All these drugs are prohibited for use during pregnancy.

How effective the treatment will be depends on the duration of use and compliance with dosage standards. It would be imprudent to discontinue therapy once symptoms have resolved. Even after pain relief, the drug must be continued until the end of the course. If you follow the regimen, you can cope with the disease quite effectively, forgetting about pain forever.

We reviewed analogues to the drug "Allopurinol", price, reviews, instructions for use.

Pharmacotherapy of gout

Treatment of gout seems to be an exhausted topic. Over the past 25 years, not a single fundamentally new anti-gout drug has been created. However, practice shows that not all issues in the treatment of gout have been resolved. One of the important problems is timely and accurate diagnosis of the disease.

The most common are the so-called Rome diagnostic criteria for gout (1961) (see box). It is necessary to make a number of comments regarding these diagnostic criteria.

They do not take into account the kidney damage that naturally occurs with gout and, in particular, the significant fact that in 40% of patients the detection of kidney stones precedes the first articular attack. The upper limits of normal uricemia given in the Rome criteria were determined using manual methods (colorimetric and enzymatic uricase). The use of the now most common automated methods for determining uric acid has led to a recalculation of normal values ​​- they increase by 0.4–1.0 mg% or by 24–60 µmol/l (see table).

Errors in the diagnosis of gout result from ignorance of the fact that during an acute attack, the level of uric acid in many patients (according to various sources, in 39–42%) decreases to normal levels.

The most reliable diagnostic method is the detection of urate crystals using polarization microscopy

. But one must take into account the relatively low sensitivity of this research method (69%), the dependence of the results on the experience and thoroughness of the microscopist, as well as on the number of crystals and their sizes. Crystals of monosodium urate in the synovial fluid can be found (usually outside the cells) in patients with joint damage of other etiologies with concurrent asymptomatic hyperuricemia, for example, in psoriatic arthritis, hyperparathyroidism, sarcoidosis, malignant tumors, renal failure.

The striking effect of colchicine, previously considered a diagnostic sign of gout, is now not considered as such, as it can be observed in pseudogout and a number of other acute arthritis.

Methods for relieving acute gouty arthritis

There are two classic approaches to relieving a gout attack: colchicine or nonsteroidal anti-inflammatory drugs (NSAIDs)

.
It is now recognized that the overall effectiveness of these two methods is the same.
The differences are only in the speed of onset of the effect and tolerability. Colchicine begins to act faster: between 12 and 48 hours (NSAIDs - between 24 and 48 hours), but undoubtedly causes side effects more often. In the only double-blind, placebo-controlled study, colchicine

proved effective in 2/3 of patients with acute gout (placebo – in 1/3 of patients); treatment was more successful if it was started within the first 24 hours after the onset of the attack. More than 80% of patients experienced nausea, vomiting, diarrhea, or abdominal pain before complete resolution of arthritis (MJ Ahbern et al.). The standard method of using colchicine for an acute attack of gout is to administer 0.5 mg of the drug every hour. Treatment is carried out until the onset of effect, the development of side effects, or the maximum dose is reached (usually no more than 6 mg over 12 hours; in patients with renal failure and the elderly, the dose should be lower).

Among NSAIDs, preference is given to the most effective in anti-inflammatory terms: previously, as a rule, phenylbutazone was prescribed (now it is almost never used due to the risk of hematological complications), currently diclofenac sodium

or
indomethacin
(in doses up to 200 mg per day). There is a known method of simultaneous use of colchicine (in low doses of 1–1.5 mg per day) and NSAIDs.

Judging by survey data from American and Canadian doctors, the vast majority of them prescribe NSAIDs for acute gouty arthritis (E. McDonald and S. Marino; M. Harris et al.). In France, on the contrary, among 750 rheumatologists surveyed, 63% prefer colchicine, 32% prefer the combined use of this drug and NSAIDs, and only 5% prefer the isolated use of NSAIDs (S. Rozenberg et al.).

There are two alternative methods for relieving a gout attack: intravenous colchicine and the use of glucocorticosteroids.

(intra-articular, orally or parenterally) or
ACTH
.

The first report of the successful intravenous use of colchicine was published in 1954. After several years of enthusiasm for this method, it was almost abandoned due to the possibility of developing severe complications (primarily inhibition of hematopoiesis), in some cases leading to death. However, even now this method is still used, for example, in the development of severe arthritis after surgery, when other anti-inflammatory drugs are contraindicated.

It is recommended to strictly adhere to the following rules

(S. Wallace and J. Singer):

• a single dose should not exceed 2 mg, and the total dose should not exceed 4 mg (usually, 1 mg of colchicine dissolved in 20 ml of isotonic sodium chloride solution is first administered for at least 10 minutes);

• if the patient received colchicine orally the day before, this drug should not be used intravenously; after intravenous administration of a full dose, colchicine should not be used in any form for at least 7 days;

• in the presence of kidney or liver disease, the dose of colchicine should be reduced (by half if creatinine clearance is below 50 ml/min; if this figure is below 10 ml/min, colchicine is not used); in elderly patients, before intravenous use of colchicine, it is advisable to study creatinine clearance (if this is not possible, the dose is halved);

• Precautions should be taken to eliminate the risk of colchicine entering outside the vein. The onset of action of intravenously administered colchicine occurs within 6–12 hours.

It is much safer to use glucocorticosteroids. In addition to the long, although infrequently practiced, intra-articular administration of these drugs, they can be taken orally: prednisolone

in the initial daily dose of 30–50 mg. After 1–2 days, the dose is quickly reduced, and after an average of 10 days the drug is discontinued. The indication for this method of relieving a gout attack is the inability to use NSAIDs or colchicine due to intolerance to these drugs, renal failure or ulcerative lesions of the gastrointestinal tract (in the latter case, corticosteroids are administered parenterally). According to one study, oral prednisolone therapy led to improvement in all patients within 48 hours; complete disappearance of arthritis symptoms in most cases was noted on average after 3.8 days and no later than 7 days. Relapse of arthritis immediately after discontinuation of prednisolone was observed in only one case. Tolerability was good, side effects (transient hyperglycemia) were detected in only 1 of 12 patients (G. Groff et al.).

Anti-gout therapy itself

Despite many years of experience in gout therapy, two fundamental points remain not completely clear:

when to start treatment for bestophous gout, and which drug is best to choose in the absence of urate hyperexcretion.

An absolute indication for starting anti-gout therapy is the detection of tophi

(see picture).
From a practical point of view, it is advisable to classify as tophi not only subcutaneous nodules, but also destructive changes typical of gout, found on radiographs of the joints, as well as characteristic changes in the kidneys (urate nephropathy and urolithiasis). The latter is especially important, since it is kidney damage that determines the prognosis of gout
in many patients.
It is recommended to carry out appropriate examinations:
x-rays of those joints that were most often attacked, kidney studies and urine tests. It is well known that gouty nephropathy is characterized by an asymptomatic course. Therefore, it is important to pay attention to even small changes in urine tests (microproteinuria, microleukocyturia, microhematuria, and, especially, persistent sharply acidic reaction of urine - pH 4.5–5.5, with a norm of 7.4–7.5), carefully study the medical history (renal colic, pain in the kidney area, gross hematuria), do not forget to monitor blood pressure and conduct an ultrasound examination of the kidneys in search of stones.

In approximately 20% of cases, stones in patients with gout are composed of calcium oxalate and calcium phosphate. However, in most cases, a central urate “core” is detected in stones of this composition (S. Noda et al.), this explains the decrease in the incidence of calcium stones during treatment with allopurinol.

There are three different opinions regarding the time to start therapy for bestophous gout. According to the first, specific therapy should be delayed until symptomatic prophylactic treatment has been exhausted or tophi formation has been noted. This opinion is justified by the fact that tophi and chronic arthritis develop only in a minority of patients with gout.

Most experts make the prescription of anti-gout therapy dependent on the frequency of gout attacks during the year, considering the number 3-4 “critical”.

The third, less common opinion is that specific therapy should be started after the first joint attack, since even after the attack subsides, microtophus and urate crystals can be detected in the synovial membrane - a sign of chronic inflammation. However, there is no convincing evidence of the development of joint destruction in asymptomatic gout. Due to the fact that in some patients a second attack of gout may occur only many years after the first, and given the seriousness of the decision to use anti-gout therapy (lifelong nature, risk of adverse reactions), this approach to the treatment of gout is not used in practice.

Preventive anti-inflammatory therapy

Most often, it involves the daily use
of colchicine
in a small daily dose (0.5–1.5 mg). Tolerability of long-term use of colchicine in these doses is usually satisfactory; side effects (mainly diarrhea) are observed in only 4% of patients. The incidence of complications increases in case of impaired renal function. It is in these patients that depression of hematopoiesis, proximal myopathy (weakness in proximal muscle groups and increased creatine phosphokinase) and peripheral neuropathy more often develop. By 1990, 16 cases of death were known from complications of low-dose colchicine therapy. It is recommended to exercise caution in patients with impaired liver function, as well as with the simultaneous use of cimetidine, tolbutamide and erythromycin (they slow down the metabolism of colchicine).

Choosing between allopurinol and uricosuric drugs

To resolve this issue, they resort to measuring the daily excretion of uric acid.

This allows us to identify that relatively small subpopulation of gout patients in whom urate excretion is increased (more than 800 mg per day in the case of a study without dietary restrictions or 600 mg after preliminary use of a low-purine diet), which is considered a sign of overproduction of uric acid. Before this study, you should ensure normal renal function (in the case of decreased creatinine clearance, a decrease in uric acid excretion does not exclude its overproduction), and also exclude possible drug effects on the excretion of urate. It is believed that in such patients only allopurinol should be used, and uricosuric drugs are dangerous due to the increased risk of developing nephropathy and urolithiasis.

Allopurinol

.
The dose of allopurinol is selected individually and can range from 100 to 800 mg per day.
It is recommended to start therapy with a relatively small dose (100–300 mg per day), avoiding a very sharp decrease in uricemia: optimally no more than 0.6–0.8 mg% for 1 month of therapy. This helps reduce the risk of developing gout attacks after prescribing anti-gout drugs (N. Yamanaka et al.). When choosing the dose of allopurinol, you need to keep in mind that the maximum effect is achieved no later than 14 days. Side effects occur in approximately 5–20% of patients, with allopurinol discontinuation required in almost half of them. The most common are allergic skin rashes (usually maculopapular in nature), dyspepsia, diarrhea and headache. Serious complications are rare and are more common in renal failure and in patients taking thiazide diuretics. The greatest danger is represented by a symptom complex considered to reflect hypersensitivity to allopurinol: a combination of dermatitis, signs of liver damage, renal dysfunction, leukocytosis, eosinophilia or hematopoietic suppression.

Since in some patients allopurinol is the only effective drug in the treatment of gout, in the event of hypersensitivity to it, “desensitization” may be necessary, sometimes allowing therapy to be resumed. This procedure is advisable for the development of mild reactions, mainly recurrent dermatitis. Aqueous suspensions of the drug are prepared in very small concentrations (0.05 mg in 1 ml). Slowly (once every 3 days) and gradually (each time no more than 2 times) the concentrations of allopurinol are increased. The entire “oral desensitization” procedure takes about 30 days (T. Gillott et al.).

If there is no hyperuricosuria, allopurinol and uricosuric drugs are equally indicated, the choice between them being determined mainly by personal preference and the experience of the physician. Almost no objective comparisons have been made to fully weigh all the advantages and disadvantages of these two groups of funds. There is an opinion that it is preferable to prescribe uricosuric drugs to patients under the age of 60 years, with satisfactory renal function (creatinine clearance of at least 50 ml/min) and in the absence of urolithiasis.

Benzbromarone

. Benzbromarone receives the most attention for the following reasons:

• it not only enhances the excretion of urates by the kidneys (inhibits tubular reabsorption), but also inhibits the synthesis of purine bases and the absorption of uric acid from the intestine;

• its dose may not be reduced in case of moderate renal failure (unlike allopurinol);

• it is not characterized by serious adverse reactions (3-4% of patients develop diarrhea and itchy skin rashes);

• the drug is easy to use (the daily dose, usually 100–200 mg, is taken once).

The benefits of benzbromarone over allopurinol have been established in two recent studies. The first, an open-label, parallel-arm study, compared the effectiveness of benzbromarone (100 mg daily) with allopurinol (300 mg daily) in 86 men with chronic gout in the absence of uric acid hyperexcretion. With the help of benzbromarone, it was possible to achieve a more significant reduction in uric acid levels than with allopurinol treatment: uricemia decreased by 5.04 and 2.75 mg%, respectively. Improvement in renal function and the absence of new stone formation was noted only in patients receiving benzbromarone (F. Perez-Ruiz et al., 1998). It should be noted that the lack of effectiveness of allopurinol found in this study could have resulted from the use of an incomplete dose of the drug (no more than 300 mg). In terms of the degree of reduction in uricemia, benzbromarone (in a daily dose of 100–200 mg) was more effective than allopurinol (100–300 mg/day) also in patients with chronic gout in the presence of renal failure (F. Perez-Ruiz et al., 1999). Moreover, benzbromarone was effective in patients receiving diuretics (in these cases, the effect of allopurinol was clearly worse), and had a sufficient effect when allopurinol was ineffective.

Other uricosurics

Probenecid, the “oldest” uricosuric drug, is still used in the treatment of gout, with the use of which in 1949 the “era” of specific therapy for this disease began.

Probenecid

prescribed at an initial dose of 0.25 g 2 times a day. If the level of uric acid in the blood is not sufficiently reduced, the dose of the drug is increased by 0.5 g every 1–2 weeks (the maximum daily dose is 3 g). The disadvantages of probenecid are the often developing resistance, as well as the relatively frequent occurrence of adverse events (about 8% of patients have gastric dyspepsia, and 5% have allergic skin rashes). Rare serious adverse reactions include liver necrosis, nephrotic syndrome and aplastic anemia. Probenecid can prolong the effect of penicillin, cephalosporins, rifampicin and a number of other drugs, and also increases the blood concentration of naproxen and indomethacin. Acetylsalicylic acid completely blocks the uricosuric effect of probenecid.

Sulfinpyrazone

is an analogue of the metabolite of phenylbutazone, which explains the possibility of developing side effects such as inhibition of hematopoiesis and liver dysfunction, and has led to a gradual reduction in the use of this drug. The initial daily dose of sulfinpyrazone is 100 mg, divided into 2 doses throughout the day. After 3–4 days, in the absence of a sufficient decrease in the level of uric acid in the blood, the daily dose is gradually (every week) increased by 100 mg (but not more than 800 mg). The drug is able to inhibit platelet aggregation, which is valuable given the frequent presence of cardiovascular diseases in patients with gout. The most common side effect is gastric dyspepsia.

In the treatment of gout, it is possible to use a combination of allopurinol with uricosuric drugs

(usually with sulfinpyrazone or benzbromarone, but not with probenecid). This method is justified in particularly severe patients, after establishing torpidity to monotherapy. In these cases, careful selection of doses of individual drugs is required, since uricosuric drugs increase the excretion of allopurinol. A combination of individual uricosuric agents is also possible. There have been no special studies evaluating the advantages and disadvantages of such combinations of anti-gout drugs.

When prescribing both allopurinol and uricosuric drugs, two important circumstances should be remembered.

First. Due to the increased excretion of uric acid, already in the first days of using these drugs, the risk of stone formation and the development of urate nephropathy increases. In this regard, a preliminary examination of the condition of the kidneys and urinary tract is necessary (determining the level of creatinine, its clearance, ultrasound examination of the kidneys), as well as a study of urine pH. Paper analyzers, usually included with commercial citrate preparations, can be used to test urine pH. In patients with persistently low urine pH

(less than 6) before prescribing anti-gout drugs,
it is advisable to achieve its alkalization by using citrates
, sodium bicarbonate or acetozolamide (carbonic anhydrase inhibitor). These drugs are used by regularly checking the pH of the urine, the optimal level of which is 6.2–6.6. In order to prevent stone formation, it is also necessary to drink plenty of fluids (diuresis should be at least 2 liters per day). Preventive measures are taken during the entire period of selecting the optimal dose of the anti-gout drug (usually at least 1–2 months).

Second. After prescribing anti-gout medications for 6–12 months, the risk of developing gout attacks increases. Therefore, as a rule, it is recommended not to start therapy if arthritis is not yet complete.

colchicine
in small doses (0.5–1.5 mg per day) or NSAIDs for several months for prophylactic purposes The use of colchicine has been shown to prevent the occurrence of acute arthritis in approximately 85% of patients who are started on anti-gout therapy. At the same time, a number of experts express doubts about the advisability of mandatory use of preventive therapy, pointing to the relatively small risk of exacerbation of gout and the potential toxicity of colchicine.

Criteria for the effectiveness of anti-gout therapy

In the first months of therapy, the main criterion for effectiveness is the achievement of an optimal level of uric acid in the blood.

. It is no more than 6 mg% (in men), and ideally 4–5 mg%. If the concentration of uric acid does not fall below 6.8 mg%, the dissolution of urate in the extracellular fluid and tissues does not occur, and the risk of gout progression remains. After 6 months of therapy, its effectiveness is also determined by the reduction of gout attacks, the resorption of subcutaneous tophi, the preservation of renal function and the absence of progression of urolithiasis.

The list of references can be found on the website https://www.rmj.ru
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