Anti-gouty drugs. Agents that inhibit the formation of uric acid.
Indications for use
Allopurinol is indicated to reduce the concentration of urates/uric acid in conditions accompanied by the accumulation of urates/uric acid deposits (for example, gouty arthritis, cutaneous tofuses, nephrolithiasis), or at a predictable clinical risk (for example, treatment of a malignant tumor can potentially lead to acute uric acid nephropathy).
The main clinical conditions in which urate accumulation/uric acid deposits may occur are:
idiopathic gout; urate urolithiasis;acute uric acid nephropathy;neoplastic and myeloproliferative diseases with a high rate of cell population renewal, in which hyperuricemia occurs spontaneously or after cytotoxic therapy; certain enzymatic disorders leading to hyperproduction of urates, for example, hypoxanthine-guanine-phosphoribosyltransferase deficiency (including Lesh-Nihen syndrome), glucose deficiency-6-phosphatases (including glycogenoses), increased activity of phosphoribosyl pyrophosphate synthetase, increased activity of phosphoribosyl pyrophosphate amideotransferase, insufficiency of adenine phosphoribosyltransferase.
Allopurinol is indicated for the treatment of urolithiasis associated with the formation of 2,8-dihydroxyadenine (2,8-DHA) concretions as a result of a decrease in the activity of adenine phosphoribosyltransferase.
Allopurinol is indicated for the treatment of recurrent urolithiasis associated with the formation of mixed calcium-oxalate concretions on the background of hyperuricosuria, when increased fluid intake, diet and other methods have proved ineffective.
Contraindications
Hypersensitivity to allopurinol or to other components of the drug.
Safety precautions
Chronic renal failure
Patients with chronic renal impairment and concomitant use of diuretics, in particular thiazides, may be at increased risk of developing hypersensitivity reactions, including SJS/TEN' associated with allopurinol. Special attention is required regarding the detection of signs of hypersensitivity syndrome or SJS/TEN and the patient should be informed of the need for immediate and discontinuation of treatment at the first appearance of symptoms.
Liver or kidney failure
In patients with hepatic or renal insufficiency, reduced doses should be used. Patients with hypertension or heart failure receiving, for example, diuretics or ACE inhibitors may have concomitant renal impairment, and allopurinol should be used with caution in this group.
Asymptomatic hyperuricemia in itself, as a rule, is not considered an indication for the use of allopurinol, since it is usually sufficient to follow an appropriate diet and an adequate drinking regime, Do not consume foods with a high purine content (for example, offal: kidneys, brain, liver, heart and tongue, meat broths and alcohol, especially beer).
Acute attack of gout
Treatment with allopurinol should not be started until the acute attack of gout is completely relieved, as further attacks may be provoked.
At the beginning of treatment with allopurinol, as with other uricosuric drugs, acute attacks of gout are possible due to the mobilization of a large amount of uric acid. Therefore, it is advisable to simultaneously use appropriate anti-inflammatory drugs (except aspirin or salicylates) or colchicine for the purpose of prevention during the first month. Detailed information about recommended doses, warnings and precautions can be found in the relevant literature.
If an acute attack of gout occurs in patients already taking allopurinol, treatment should be continued at the same dose, and the acute attack should be treated with appropriate anti-inflammatory drugs.
Xanthine deposits
In cases where the intensity of urate formation increases significantly (for example, malignant diseases and their therapy, Lesh-Nihen syndrome), the absolute concentration of xanthine in urine may, in rare cases, reach levels that contribute to the deposition of xanthine in the urinary tract. This risk can be minimized by adequate hydration to achieve optimal dilution of urine by alkalinizing urine.
Blockage of the urinary tract by kidney stones of uric acid
With adequate therapy with allopurinol, it is possible for large urate stones to dissolve in the renal pelvis, enter the urinary tract (renal colic) with possible blockage.
Lactose intolerance
Allopurinol tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not take the drug.
Method of application and dosage
Take after meals, without chewing, with plenty of water.
Adults
To reduce the risk of adverse reactions, treatment begins with a low dose, for example, 100 mg / day, which is increased only in case of an insufficient response decrease in the concentration of urates in the blood serum.
Special care should be taken in case of impaired renal function (see subsection "Patients with impaired renal function").
When selecting the dose of the drug, it is recommended to use the following dosage regimens:
100-200 mg per day for mild course of the disease; 300-600 mg per day for moderate course of the disease; 700-900 mg per day for severe course of the disease.
If the calculation of the dose must be based on the patient's body weight, then the dose should be from 2 to 10 mg / kg / day.
Pediatric population
Children under 15 years of age: 10-20 mg / kg of body weight per day up to a maximum daily dose of 400 mg.
Allopurinol is used in children in rare cases, with the exception of oncological diseases (especially leukemia) and some enzymatic disorders (for example, Lesh-Nihen syndrome).
Elderly patients
In the absence of specific data, the minimum effective doses should be used to ensure a sufficient decrease in the concentration of urates in the blood serum. Special attention should be paid to recommendations on the selection of the dose of the drug for patients with impaired renal function and some other conditions (see the subsection "Patients with impaired renal function" and the section "Precautions").
Patients with impaired renal function
Since allopurinol and its metabolites are excreted from the body by the kidneys, impaired renal function can lead to a delay in the drug and/or its metabolites, followed by an extension of their half-life from blood plasma. In severe renal insufficiency, it is advisable to use Allopurinol at a dose of less than 100 mg per day or use single doses of 100 mg at intervals of more than one day.
If it is possible to control the concentration of oxypurinol in blood plasma, then the dose of Allopurinol should be adjusted so as to maintain the level of oxypurinol in blood plasma below 100 mmol/l (15.2 mg/l).
Allopurinol and its metabolites are removed from the body by hemodialysis. If hemodialysis is required 2-3 times a week, then an alternative treatment regimen should be considered — taking 300-400 mg of Allopurinol immediately after completion of each hemodialysis session (the drug is not taken between temodialysis sessions).
Patients with impaired liver function
Reduced doses should be used in patients with impaired liver function. In the early stages of therapy, periodic monitoring of laboratory parameters of liver function is recommended.
Treatment of conditions with high urate metabolism, for example, neoplasia, Lesh-Nihen syndrome
It is advisable to correct existing hyperuricemia and/ or hyperuricosuria with Allopurinol before starting cytotoxic therapy. It is important to ensure adequate hydration to maintain optimal diuresis, as well as to ensure urine alkalinization to increase urate/uric acid solubility in urine. The dosage of Allopurinol should be at the lower limit of the recommended dose range.
If kidney function is compromised by the development of uric acid nephropathy OR other renal pathology, then treatment should be continued in accordance with the recommendations provided in the subsection "Patients with impaired renal function".
These measures can reduce the risk of deposition of xanthine and/or uric acid, complicating the course of the disease.
Recommendations for monitoring
To establish the optimal dose of the drug, it is necessary to periodically monitor the concentration of urates in the blood serum, as well as the level of urates / uric acid in the urine.
Method of application
Tablets for oral administration. Allopurinol can be taken 1 time a day after meals. The drug is well tolerated, especially after meals. If the daily dose exceeds 300 mg and gastrointestinal disorders occur, it is advisable to divide the dose into several doses.
overdose
It has been reported that 22'5 g of allopurinol was taken without the development of adverse reactions. The occurrence of nausea, vomiting, diarrhea, and dizziness was observed in a patient who took allopurinol. General supportive measures are being taken to restore the condition. Massive absorption of allopurinol can lead to a significant inhibition of xanthine oxidase activity, which should not cause any undesirable effects, except for the effect on concomitant therapy, especially with 6-mercaptopurine and/or azathioprine. Adequate hydration to maintain optimal diuresis promotes the excretion of allopurinol and its metabolites. If necessary, hemodialysis is possible.
side effect
The most common side effects of allopurinol are skin rashes. Undesirable effects may vary in frequency depending on the dose received, on the disease, as well as when used in combination with other drugs. The frequency of adverse reactions increases with disorders of the kidneys and / or liver.
At the beginning of treatment with allopurinol, reactive gout attacks may occur due to the mobilization of uric acid from gouty nodules and other depots.
The adverse reactions described below are classified by organs and systems and by their frequency: very common (≥10%); common (≥1% and <10%); infrequent (≥0.1% and <1%); rare (≥0.01% and <0.1%); very rare (<0.01%).
Infections and infestations
Very rarely — furunculosis.
Blood system and lymphatic system
Very rarely — thrombocytopenia 1' agranulocytosis 1' aplastic anemia.
Leukopenia, leukocytosis, zosinophilia, hemolytic anemia, blood clotting disorders, and acute pure erythrocyte aplasia associated with allopurinol therapy have been reported.
The immune system
Infrequently — hypersensitivity reactions 2;
very rarely — angioimmunoblastic T-cell lymphoma 3.
Metabolic disorders
Very rarely — diabetes mellitus, hyperlipidemia. At the beginning of treatment, reactive gout attacks are possible.
very rarely — agioedema 7, drug-induced erythema, alopecia, hair discoloration.
Urinary system
Very rarely — interstitial nephritis, hematuria, azotemia, nephrolithiasis.
Disorders of the reproductive system and mammary glands
Very rarely — gynecomastia, erectile dysfunction, male infertility, nocturnal emission.
General violations
Very rarely — asthenia, fevers8, feeling unwell, edema, myopathy/myalgia, xanthine deposits in tissues, including muscles.
1 Thrombocytopenia, agranulocytosis and aplastic anemia have been very rarely reported, especially in patients with impaired renal and/or liver function, which underscores the need for special attention to this group of patients.
2 Serious hypersensitivity reactions, including skin reactions associated with exfoliation, fever, lymphadenopathy, pseudopymphoma, arthralgia, leukopenia, and/or eosinophilia (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) occur rarely (see "Skin and subcutaneous tissue").
Hypersensitivity reactions associated with vasculitis and tissue reactions can have various manifestations, including hepatosplenomegaly, hepatitis, biliary tract disappearance syndrome (destruction and disappearance of intrahepatic bile ducts), renal failure and, very rarely, seizures. There may be disorders from other organs (for example, liver, lungs, kidneys, pancreas, myocardium, colon). Acute anaphylactic shock has been very rarely reported. These reactions can occur at any time of treatment, and if they occur, allopurinol should be IMMEDIATELY and PERMANENTLY discontinued.
The resumption of the drug should not be carried out in patients with hypersensitivity syndrome, SJS/TEN. Corticosteroids may be effective for relieving skin hypersensitivity reactions. Generalized hypersensitivity reactions, especially fatal ones, usually developed in patients with impaired renal and/or liver function.
3angioimmunoblastic T-cell lymphoma is very rarely diagnosed after a lymph node biopsy for generalized lymphadenopathy.
4IN early clinical studies, nausea and vomiting have been reported. Further observations showed that these reactions are not a serious problem, they can be avoided by taking Allopurinol after eating.
5disfunction of the liver (usually reversible when the drug is discontinued) may occur without obvious signs of generalized hypersensitivity reactions.
6 Skin reactions are the most common reactions and can occur during any period of treatment. These reactions may be accompanied by itching, rashes may be maculopapular, sometimes bran-like, purpura may develop, very rarely exfoliative dermatoses such as Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) may develop. The highest risk of SJS, TEN, or other serious hypersensitivity reactions occurs in the first weeks of treatment. The best results in the treatment of such reactions are observed with early diagnosis and immediate discontinuation of any suspected drug. With the development of such reactions, Allopurinol should be stopped immediately. If the skin reaction is mild, then after the symptoms disappear, you can re-prescribe the drug in a low dose (for example, 50 mg / day), gradually increasing it if necessary. If a skin rash reappears, the drug should be discontinued forever, since severe generalized hypersensitivity reactions may occur. If SJS/TEN or other serious hypersensitivity reactions cannot be excluded, treatment with allopurinol cannot be resumed due to the risk of severe or fatal reactions. The clinical diagnosis of SJS/TEN is the basis for decision-making. If such reactions occur at any point during treatment, allopurinol should be discontinued immediately and permanently.
7 Cases of angioedema with and without symptoms of generalized hypersensitivity reactions have been reported.
8 Cases of fever with and without symptoms of generalized hypersensitivity reactions have been reported.
Shelf
life is 5 years
Do not use the drug after the expiration date indicated on the package.
Storage conditions
In the original packaging at a temperature not exceeding 25 ° C.