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.
Allopurinol
There are no current clinical data to determine the incidence of side effects. Their frequency may vary depending on the dose and whether the drug was prescribed as monotherapy or in combination with other drugs. The classification of the frequency of side effects is based on an approximate estimate; for most side effects there is no data to determine the frequency of their development.
The classification of adverse reactions depending on the frequency of occurrence is as follows: very common (≥1/10), common (from ≥1/100 to <1/10), uncommon (from ≥1/1000 to <1/100), rare (from ≥1/10000 to <1/1000), very rare (<1/10000), frequency unknown (cannot be determined from available data).
Adverse reactions associated with allopurinol therapy observed in the post-marketing period are rare or very rare. In the general patient population, most cases are mild. The incidence of adverse events increases with impaired renal and (or) liver function.
Infections and parasitic diseases
:
very rare:
furunculosis.
Blood and lymphatic system disorders
:
very rare:
agranulocytosis, aplastic anemia, thrombocytopenia, granulocytosis, leukopenia, leukocytosis, eosinophilia and red blood cell only aplasia.
Thrombocytopenia, agranulocytosis and aplastic anemia have been reported very rarely, particularly in persons with impaired renal and/or hepatic function, highlighting the need for special caution in these patient groups.
Immune system disorders
:
infrequent:
hypersensitivity reactions;
rare:
severe hypersensitivity reactions, including skin reactions with epidermal detachment, fever, lymphadenopathy, arthralgia and/or eosinophilia (including Stevens-Johnson syndrome and toxic epidermal necrolysis) (see section "Skin and subcutaneous tissue disorders").
Associated vasculitis or tissue reactions may have a variety of manifestations, including hepatitis, renal involvement, acute cholangitis, xanthine stones, and, in very rare cases, seizures.
In addition, the development of anaphylactic shock was very rarely observed.
If severe adverse reactions develop, allopurinol therapy should be stopped immediately and not restarted.
In delayed multiorgan hypersensitivity (known as drug hypersensitivity syndrome /DRESS), the following symptoms may develop in various combinations: fever, skin rash, vasculitis, lymphadenopathy, pseudolymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly, changes in liver function tests, vanishing biliary syndrome ducts (destruction or disappearance of intrahepatic bile ducts). If such reactions develop during any period of treatment, Allopurinol should be immediately discontinued and never restarted.
Generalized hypersensitivity reactions developed in patients with impaired renal and (or) liver function. Such cases were sometimes fatal;
very rare:
angioimmunoblastic lymphadenopathy.
Angioimmunoblastic lymphadenopathy has very rarely been diagnosed after lymph node biopsy for generalized lymphadenopathy. Angioimmunoblastic lymphadenopathy is reversible and regresses after cessation of allopurinol therapy.
Metabolic and nutritional disorders
:
very rare:
diabetes mellitus, hyperlipidemia.
Mental disorders
:
very rare:
depression.
Nervous system disorders
:
very rare:
coma, paralysis, ataxia, neuropathy, paresthesia, drowsiness, headache, perversion of taste.
Visual disorders
:
very rare:
cataracts, visual impairment, macular changes.
Hearing and labyrinth disorders
:
very rare:
dizziness (vertigo).
Heart disorders
:
very rare:
angina, bradycardia.
Vascular disorders
:
very rare:
increased blood pressure.
Gastrointestinal disorders
:
infrequent:
vomiting, nausea, diarrhea;
Nausea and vomiting were observed in earlier clinical studies, but more recent observations have confirmed that these reactions are not a clinically significant problem and can be avoided by administering allopurinol after meals.
very rare:
recurrent hematemesis, steatorrhea, stomatitis, changes in bowel movements;
frequency unknown:
abdominal pain.
Disorders of the liver and biliary tract
:
infrequent:
asymptomatic increase in the concentration of liver enzymes (increased levels of alkaline phosphatase and transaminases in the blood serum);
rare:
hepatitis (including necrotizing and granulomatous forms).
Liver dysfunction may develop without obvious signs of generalized hypersensitivity.
Skin and subcutaneous tissue disorders
:
frequent:
rash;
rare:
severe skin reactions: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN);
very rare:
angioedema, local drug rash, alopecia, hair bleaching.
Skin adverse reactions are the most common in patients taking allopurinol. During drug therapy, these reactions can develop at any time. Skin reactions may include itching, maculopapular and scaly rashes. In other cases, purpura may develop. In rare cases, exfoliative skin lesions (SSD/TEN) are observed. If such reactions develop, allopurinol therapy should be discontinued immediately. If the skin reaction is mild, then allopurinol can be resumed at a lower dose (for example, 50 mg per day) after these changes have resolved. Subsequently, the dose can be gradually increased. If skin reactions recur, allopurinol therapy should be stopped and not restarted, since further use of the drug may lead to the development of more severe hypersensitivity reactions (see “Immune system disorders”).
According to existing information, during therapy with allopurinol, angioedema developed in isolation, as well as in combination with symptoms of a generalized hypersensitivity reaction.
Musculoskeletal and connective tissue disorders:
very rare:
myalgia.
Renal and urinary tract disorders
:
very rare:
hematuria, renal failure, uremia;
frequency unknown:
urolithiasis disease.
Reproductive system and breast disorders
:
very rare: male infertility, erectile dysfunction, gynecomastia.
General disorders and disorders at the injection site
:
very rare: swelling, general malaise, general weakness, fever.
According to existing information, during therapy with allopurinol, fever developed both in isolation and in combination with symptoms of a generalized hypersensitivity reaction (see “Immune system disorders”).
Reports of possible adverse reactions
If adverse reactions occur, including those not listed in this instruction, you should stop using the drug.
In the post-registration period, any information about possible adverse reactions is important, since these reports help to continuously monitor the safety of the drug. Healthcare professionals are required to report any suspected adverse reactions to local pharmacovigilance authorities.
Allopurinol tab 300 mg N30 (Organic)
Azathioprine is metabolized to form 6-mercaptopurine, which is inactivated by the enzyme xanthine oxidase. When 6-mercaptopurine or azathioprine therapy is combined with allopurinol, patients should be given only one-fourth the usual dose of 6-mercaptopurine or azathioprine because inhibition of xanthine oxidase activity increases the duration of action of these compounds. Vidarabine (adenine arabinoside) The half-life of vidarabine is increased in the presence of allopurinol. When these drugs are used concomitantly, particular caution should be exercised regarding increased toxic effects of therapy. Salicylates and uricosurics The main active metabolite of allopurinol is oxypurinol, which is excreted by the kidneys in a manner similar to uric acid salts. Therefore, drugs with uricosuric activity, such as probenecid or high doses of salicylates, may increase the elimination of oxypurinol. In turn, increased excretion of oxypurinol is accompanied by a decrease in the therapeutic activity of allopurinol, however, the significance of this type of interaction must be assessed individually in each case. Chlorpropamide With the simultaneous use of allopurinol and chlorpropamide, in patients with impaired renal function, the risk of developing prolonged hypoglycemia increases, since allopurinol and chlorpropamide compete with each other at the stage of tubular excretion. Anticoagulants coumarin derivatives When used simultaneously with allopurinol, an increase in the effects of warfarin and other anticoagulants coumarin derivatives was observed. In this regard, it is necessary to carefully monitor the condition of patients receiving concomitant therapy with these drugs. Phenytoin Allopurinol is capable of inhibiting the oxidation of phenytoin in the liver, but the clinical significance of this interaction has not been established. Theophylline Allopurinol is known to inhibit the metabolism of theophylline. This interaction can be explained by the participation of xanthine oxidase in the process of theophylline biotransformation in the human body. Serum theophylline concentrations should be monitored when initiating concomitant therapy with allopurinol, as well as when increasing the dose of the latter. Ampicillin and amoxicillin An increased incidence of skin reactions was reported in patients concomitantly receiving ampicillin or amoxicillin and allopurinol compared to patients who did not receive such concomitant therapy. The cause of this type of drug interaction has not been established. However, in patients receiving allopurinol, other antibacterial drugs are recommended instead of ampicillin and amoxicillin. Cytotoxic drugs (cyclophosphamide, doxorubicin, bleomycin, procarbazine, mechlorethamine) In patients suffering from tumor diseases (except leukemia) and receiving allopurinol, increased suppression of bone marrow activity by cyclophosphamide and other cytotoxic drugs was observed. However, according to the results of controlled studies involving patients receiving cyclophosphamide, doxorubicin, bleomycin, procarbazine and/or mechlorethamine (chlormethine hydrochloride), concomitant therapy with allopurinol did not increase the toxic effects of these cytotoxic drugs. Cyclosporine According to some reports, the concentration of cyclosporine in the blood plasma may increase during concomitant therapy with allopurinol. When using these drugs simultaneously, the possibility of increased toxicity of cyclosporine must be taken into account. Didanosine In healthy volunteers and HIV-infected patients receiving didanosine, during concomitant therapy with allopurinol (300 mg per day), an approximately two-fold increase in didanosine Cmax (maximum drug concentration in blood plasma) and AUC (area under the concentration-time curve) was observed. . The half-life of didanosine did not change. In general, simultaneous use of these drugs is not recommended. If concomitant therapy is unavoidable, a dose reduction of didanosine and careful monitoring of the patient may be necessary. ACE inhibitors Concomitant use of ACE inhibitors with allopurinol is accompanied by an increased risk of leukopenia, so these drugs should be combined with caution. Thiazide diuretics Concomitant use of thiazide diuretics, including hydrochlorothiazide, may increase the risk of allopurinol-related hypersensitivity side effects, especially in patients with impaired renal function.
Allopurinol
Use during pregnancy and breastfeeding
Contraindicated for use during pregnancy and lactation (breastfeeding).
Use for liver dysfunction
Contraindication: severe liver dysfunction. Allopurinol should be used with caution in case of liver dysfunction (dose reduction is necessary).
Use for renal impairment
Contraindication: severe renal dysfunction. Allopurinol should be used with caution in case of impaired renal function (dose reduction is necessary).
Use in children
In children, it is used only for malignant neoplasms (especially leukemia), as well as for certain enzyme disorders (Lesch-Nychen syndrome).
The dosage regimen is set individually, under the control of the concentration of urates and uric acid in the blood and urine: children under 15 years of age - 10-20 mg/kg/day or 100-400 mg/day.
special instructions
Allopurinol should be used with caution in case of impaired liver and/or kidney function (in both cases a dose reduction is necessary), hypothyroidism. During the initial period of allopurinol therapy, systematic assessment of liver function parameters is necessary.
During treatment with allopurinol, the daily amount of fluid consumed should be at least 2 liters (under the control of diuresis).
At the beginning of the course of treatment for gout, an exacerbation of the disease may occur. For prevention, you can use NSAIDs or colchicine (0.5 mg 3 times a day). It should be taken into account that with adequate therapy with allopurinol, large urate stones in the renal pelvis may dissolve and subsequently enter the ureter.
Asymptomatic hyperuricemia is not an indication for the use of allopurinol.
In children, it is used only for malignant neoplasms (especially leukemia), as well as for certain enzyme disorders (Lesch-Nychen syndrome).
To correct hyperuricemia in patients with tumor diseases, allopurinol is recommended before starting treatment with cytostatics. In such cases, the minimum effective dose should be used. In addition, in order to reduce the risk of xanthine deposition in the urinary tract, measures must be taken to maintain optimal diuresis and alkalinization of urine. With the simultaneous use of allopurinol and cytostatics, more frequent monitoring of peripheral blood patterns is necessary.
During the period of taking allopurinol, alcohol consumption is not allowed.
Impact on the ability to drive vehicles and operate machinery
Use with caution in patients whose activities require high concentration and rapid psychomotor reactions.
