Instructions for use ALLOPURINOL
The use of the drug by patients with renal failure, as well as with hematopoietic disorders, should be under constant medical supervision.
Skin reactions are the most common reactions and can occur at any time during treatment; if they occur, allopurinol should be discontinued immediately. After symptoms have reduced, the drug can be prescribed in low doses (for example, 50 mg / day), gradually increasing the dose if necessary. If the skin rash recurs, the drug should be discontinued permanently, as severe generalized hypersensitivity reactions may occur.
There have been reports of life-threatening skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis) with the use of allopurinol. Patients should be informed of the signs and symptoms of skin reactions and monitored closely. The highest risk of developing Stevens-Johnson syndrome and toxic epidermal necrolysis is during the first weeks of treatment.
If signs or symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis occur (eg, progressive skin rash, often with blisters, or mucosal lesions), Allopurinol 100 mg tablets should be discontinued immediately.
The best results in the treatment of Stevens-Johnson syndrome or toxic epidermal necrolysis have been obtained with early diagnosis and immediate discontinuation of the suspected drug. Early discontinuation of Allopurinol 100 mg tablets is associated with a better prognosis.
If a patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis while taking Allopurinol, 100 mg tablets, the use of Allopurinol, 100 mg tablets should not be resumed.
Vasculitis and tissue reactions associated with hypersensitivity reactions can have various manifestations, incl. hepatitis, kidney damage (interstitial nephritis) and, very rarely, seizures. These reactions can occur at any time during treatment; if they occur, the drug should be discontinued immediately.
The ability to influence the reaction rate when driving vehicles or other mechanisms.
During the period of use of Allopurinol, it is necessary to refrain from driving vehicles and other mechanisms due to the possibility of dizziness or drowsiness.
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Gout
Gout is a systemic tophi disease characterized by the deposition of monosodium urate crystals in various tissues and the resulting inflammation in individuals with hyperuricemia (increased levels of uric acid) caused by environmental and/or genetic factors.
Gout is a disease that, except in rare cases and unlike other chronic arthritis, is highly treatable. In the absence of advanced and irreversible cases of renal failure, with proper management of the patient and its adequacy, almost complete reverse development of the disease process is possible. If this does not happen, then there is reason to doubt the reliability of the diagnosis of gout. Therapy includes: treatment of arthritis (acute or chronic), therapy aimed at reducing uric acid levels, diet, lifestyle changes. What do doctors usually do to make a diagnosis? Typically, an X-ray of the inflamed joint and a serum uric acid (UA) level are performed. If a fracture is suspected or there is a history of trauma, an x-ray examination may be useful, but it will not be possible to diagnose early gout with its help, since its typical signs appear later and are x-ray-negative tophi, which are called the “piercer symptom.” Intraosseous tophi appear on average at the 7th–8th year of the disease, when their diagnostic value is lost due to the presence of tophi in visible localizations. Moreover, the percentage of discrepancies in the assessment of radiographs - whether they are tophi or pseudocysts in osteoarthritis - is high even at a late stage of the disease.
Determining the level of UA also does not help determine the diagnosis: hyperuricemia is a common symptom of other arthritis, the onset of which may be similar to the onset of gout (pyrophosphate arthropathy, osteoarthritis, psoriatic arthritis). It is also difficult to use these data for further selection of antihyperuricemic therapy, since urinary levels decrease during an attack of arthritis and it will be difficult to assess the effectiveness of allopurinol in the future. In this regard, the main task during this period is to quickly and safely relieve arthritis.
Arthritis treatment
Important! 1. Avoid alcohol during an attack (it helps to increase the duration of the attack, there is an undesirable interaction with medications). 2. Drink plenty of liquid: green tea, mineral water, unsweetened berry fruit drinks. 3. Home regimen (due to severe pain, blood pressure may rise, there is a risk of developing cardiovascular accidents). 4. Follow a strict diet. 5. Do not wait for the attack to resolve itself, start effective therapy. One of the drugs that has a rapid onset of anti-inflammatory effect is nimesulide. Drugs such as artrosilene and arcoxia have proven themselves well in the treatment of gouty arthritis. The use of glucocorticoids (GC) in acute gouty arthritis
Intra-articular administration of GC for gouty arthritis on an outpatient basis is a well-known approach recommended by the European League of Rheumatology. Colchicine Colchicine is prescribed mainly when there are contraindications to taking NSAIDs or when they are ineffective. High doses of colchicine lead to the development of side effects, while low doses (0.5 mg 1–3 times/day) are safe and can be prescribed to a number of patients with acute gouty arthritis. Unfortunately, colchicine is currently not available in the Russian Federation. However, patients can bring it from other countries.
Allopurinol
Allopurinol (Milurit) does not have a direct analgesic effect, so during an exacerbation of gout it is useless for pain relief. BUT: regular use of this drug helps eliminate pain in the future
Allopurinol tablets are taken orally after meals. The daily dose of the medicine is calculated by the doctor, taking into account the severity of the disease and the concentration of uric acid in the blood.
Treatment is usually started with minimal doses, gradually increasing them to the required level under the control of a blood test.
If you take Allopurinol, strictly following the doctor’s recommendations, then after six months or a year you can notice significant progress: the intensity and frequency of attacks of gouty arthritis becomes less and less frequent, tophi begin to resolve and soften (nodules limited by connective tissue - deposits of uric acid salts).
Treatment with Allopurinol is a long-term and continuous process. It is possible, although not advisable, to take a break for 2-3 weeks, but subject to normal blood and urine counts and only with the permission of a doctor.
It is not recommended to interrupt the medication on your own, since when Allopurinol is discontinued, the level of uric acid begins to increase already on the 3-4th day.
You cannot start treatment with these drugs during an acute attack; treatment is carried out only in the interictal period!!!
Treatment of associated conditions For patients with gout and arterial hypertension It is important to know: 1. All diuretics increase the level of sUA. 2. Diuretics prescribed for health reasons (heart failure) to patients with gout must be compensated by taking allopurinol, which requires observation by a rheumatologist in order to titrate the dose. 3. If the patient has uncomplicated hypertension, it is advisable to discontinue diuretics. The tactics of patient management should be almost the same when prescribing anticoagulants, which also help increase the level of sUA. The prescription of drugs “friendly” to MK - losartan, metformin, fenofibrate, vitamin C - is carried out in accordance with the indications for the use of these drugs.
Purina Diet Patients should avoid eating foods high in purines, which include seafood and offal (offal). Meat has a relatively high purine content, but this depends on how it is prepared. Thus, patients with gout are not recommended to consume rich soups, as well as jelly, jellied meat, sausages, etc., but they can eat meat boiled in several waters. Mushrooms and plant foods such as asparagus, cauliflower, spinach, lentils and soy are also rich in purines, but recent studies have shown that consuming plant purines does not increase blood levels of uric acid and does not lead to the development of gout. The production of endogenous purines increases with the consumption of large amounts of protein, so the diet of a patient with gout should limit proteins of animal origin. On the other hand, the amount of protein should be at least 1.5 g per 1 kg of weight to prevent and reduce the effects of fatty liver disease. Recent large studies have shown that consuming low-fat dairy products leads to lower UA levels and a reduced incidence of gout. This is due to the fact that the proteins casein and lactalbumin contained in dairy products increase the excretion of sUA in the urine. Alcohol. One of the main risk factors for developing gout is alcohol. It is necessary to exclude the consumption of beer, port wine, strong alcoholic drinks (whisky, cognac, etc.). As the results of recent studies have shown, drinking a glass (250 ml) of wine per day did not lead to an increase in the level of sUA in the blood. However, the grapes from which dry wine is produced contain a lot of fructose, which contributes to hyperuricemia, so drinking more wine per day is fraught with an increase in uric acid levels and an exacerbation of the disease. At least three days a week should be alcohol-free. Alcohol may increase sUA levels by not only increasing urate production but also decreasing renal clearance. In particular, acute alcoholic excess causes a decrease in urate excretion. Chronic alcohol consumption stimulates the production of purines. The nature of the alcohol also matters. Thus, the purine components of beer cause hyperproduction of urates. The components of whiskey, port wine and other strong alcoholic drinks include lead, which reduces the excretion of sUA. Alcohol can affect the metabolism of drugs. Alcohol consumption reduces the effect of allopurinol due to suppression of the formation of its active metabolite, oxypurinol, which is associated with the low effect of allopurinol in patients with gout who continue to drink alcohol. To prevent stone formation, patients with gout should receive enough fluid to produce at least 2 liters of urine per day. It is allowed to drink water, including mineral water, skim milk, citrus juices and berry fruit drinks, tea and coffee. Green tea has a powerful uricosuric effect. Drinking 5 or more cups of coffee per day has also been shown to have a moderate but significant uricosuric effect. Long-term coffee consumption is associated with a reduced risk of developing gout. Carbohydrates. Currently, the negative effects of fructose contained in drinks and foods are known, which, unlike other sugars, increases sUA levels. Thus, it was shown that in people who ate 5 apples at the same time, the level of UA increased by 35% (due to fructose). Recent studies have demonstrated a direct link between fructose intake and the development of gout in men. On the contrary, taking vitamin C leads to a decrease in the level of sUA in the blood due to increased excretion of sUA in the urine. In general, studies have shown that weight loss caused by reducing carbohydrate intake and increasing the amount of protein and unsaturated fats leads to a decrease in sUA levels and the incidence of gout attacks.
Indications for use of the drug Allopurinol
Diseases accompanied by hyperuricemia, including primary and secondary gout, urolithiasis (with the formation of urate), primary and secondary hyperuricemia, which occurs during pathological processes accompanied by increased breakdown of nucleoproteins and increased levels of uric acid in the blood, including various hemoblastomas (acute leukemia, lymphosarcoma, etc.), conditions during cytostatic and radiation therapy of tumors, psoriasis, massive therapy with corticosteroid drugs. There is evidence of the use of the drug in the complex treatment of epilepsy in children (increasing serotonin biosynthesis).
Indications and contraindications for taking Allopurironol
The main indications for prescribing the drug are the following conditions:
- Gout and kidney stones (pathologies accompanied by hyperuricemia).
- Psoriasis.
- Hemoblastoses (acute and chronic leukemia, lymphosarcoma).
- Urinary nephropathy and concomitant renal failure.
There are a number of absolute and relative contraindications to taking Allopurinol. The first include:
- Chronic kidney disease.
- Acute attack of gout.
- Pregnancy and breastfeeding period.
- Allergic reactions to one or more substances included in the drug.
- Hemochromatosis.
Relative contraindications are diabetes mellitus types 1 and 2, as well as arterial hypertension with high cardiovascular risk.
Possible adverse reactions and symptoms of overdose
Adverse effects when taking Allopurinol can occur in various organs and systems, so side effects should be classified into groups:
- On the part of sensitive analyzers: visual impairment, amblyopia, allergic conjunctivitis, taste perversion.
- Gastrointestinal tract: dyspeptic syndrome, cholestasis, enlarged liver, hepatitis, hepatonecrosis.
- CVS: decreased heart rate, hypertension, vasculitis, pericarditis.
- From the central and peripheral nervous system: drowsiness or insomnia, paresis, disturbances in the emotional state, neuritis, paresthesia.
- Musculoskeletal system: pain in muscles and joints.
- Hematopoietic organs: anemia, thrombocyto-, leuko- and pancytopenia.
- From the urinary and reproductive systems: edema, increased urea concentration, nephritis, impotence, enlarged mammary glands, changes in libido, infertility.
An overdose of the drug is accompanied by weakness, dizziness and typical symptoms of poisoning (nausea, vomiting, loose stools). It is also possible to reduce the daily volume of urine excreted.
Drug interactions Allopurinol
When treating hemoblastomas with antitumor drugs (methotrexate, mercaptopurine, etc.), it should be taken into account that the simultaneous use of Allopurinol not only inhibits the enzymatic oxidation of these drugs and enhances their antitumor activity, but also significantly increases toxicity. Doses of antitumor drugs in such cases should be reduced by 50%. Under the influence of Allopurinol, it is also possible to enhance the effects (including unwanted) of indirect anticoagulants, antipyrine, diphenine, theophylline, since their inactivation in the liver slows down. When used simultaneously with ampicillin drugs, the risk of developing a skin rash increases. Under the influence of thiazide diuretics, furosemide, ethacrynic acid, the antihyperuricemic effect of Allopurinol is weakened, since these drugs increase the level of uric acid in the blood plasma. Allopurinol should not be used in combination with iron-containing drugs due to the possible accumulation of iron in the liver.
