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.
Allopurinol-Egis
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),
frequent (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, syndrome disappearing bile ducts (destruction or disappearance of intrahepatic bile ducts).
If such reactions develop during any period of treatment, Allopurinol-EGIS 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, taste disturbance
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: uncommon:
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.
Nocturnal and urinary tract disorders:
very rare:
hematuria, renal failure, uremia,
frequency unknown:
urolithiasis.
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.
Instructions for use of the drug
Tablets are always taken orally with plenty of liquid and always after meals. The dosage, frequency and duration of administration are selected by the doctor and depend on the pathology.
For gout, the daily dose can vary from 200 to 600 milligrams of Allopurinol. In this case, the severity and degree of the disease are the main criteria for selecting the amount of medication.
For urate nephropathy and oncology, the drug is taken in the amount of 600-800 mg per day.
If it is necessary to prescribe medication to children, the dosage is calculated based on body weight. It is recommended to prescribe from 5 to 10 mg per kilogram of body weight per day, depending on the type and severity of the disease. Under the age of 15 years, the daily dosage should not exceed 300 milligrams.
Reviews about Allopurinol
Most of the patient reviews about the drug are positive. Consumers note the high effectiveness of the drug, rapid relief of symptoms of the disease, and a noticeable decrease in the level of uric acid in the blood according to test results. Patients also note that the drug works better as part of complex therapy and when following a diet.
However, there are also reviews of a different nature on the Internet, both neutral and negative. For some patients, Allopurinol either did not help or caused undesirable reactions, which served as a reason to cancel the course of treatment.
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.
