Pharmacological properties of the drug Allopurinol
Allopurinol is an anti-gout drug that inhibits the synthesis of uric acid and its salts in the body. The drug has the specific ability to inhibit the enzyme xanthine oxidase, which is involved in the conversion of hypoxanthine to xanthine and xanthine to uric acid. As a result, the urate content in the blood plasma is reduced and their deposition in tissues and kidneys is prevented. When using the drug, the excretion of uric acid in the urine decreases and the excretion of more easily soluble hypoxanthine and xanthine increases. Allopurinol in the body is converted into alloxanthin, which also prevents the formation of uric acid, but is inferior in terms of activity to allopurinol. After oral administration, about 90% of the drug is absorbed in the digestive tract. The maximum concentration of allopurinol in the blood plasma is achieved on average after 1.5 hours. The half-life of allopurinol is 1–2 hours, alloxanthin is about 15 hours, so inhibition of xanthine oxidase activity can last for 24 hours after a single dose of the drug. About 20% of the dose taken is excreted in feces, the rest of the drug and its metabolites are excreted in urine.
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).
Use of the drug Allopurinol
- inside after meals. Doses are set depending on the concentration of uric acid in the blood. The minimum daily therapeutic dose for adults is 0.1 g, the maximum is 0.8 g. Usually, for moderate hyperuricemia (70–100 mg/l), 0.2–0.4 g/day is prescribed 1–2 times a day. for 2–3 weeks, then switch to a maintenance dose of 0.2–0.3 g/day in 2–3 divided doses. In severe forms of gout, significant deposits of urate in tissues and severe hyperuricemia (over 80–100 mg/l), the drug is prescribed in fractions (no more than 0.2 g per dose) up to 0.6–0.8 g/day for 2– 4 weeks, and then switch to maintenance doses - 0.1–0.3 g / day, which are taken long-term, for several months. When using the drug to prevent hyperuricemia during radiation therapy and chemotherapy of tumors, the average daily dose is 0.4 g. The drug is taken 2-3 days before the start of therapy (or simultaneously) and continued for several more days after the end of specific therapy. For children under 6 years of age, the drug is prescribed at a daily dose of 5 mg/kg body weight; from 6 to 10 years - 10 mg/kg/day. The frequency of administration is 3-4 times a day. For complex treatment of epilepsy in children, the dose of the drug is 4–5 mg/kg 2 times a day for 10 days; the break between repeated courses is 1.5–2 months. If you miss the time to take the drug, take the next dose as quickly as possible. If the next dose of the drug is planned after 12 hours or more, it is necessary to take Allopurinol immediately, and the next dose at the appointed time. If there are less than 12 hours left before the next dose, the dose should be skipped and treatment should continue as usual.
Allopurinol tablets 100 mg No. 10x5
Name
Allopurinol tablet 100 mg in blister pack No. 10x5 Basic physical and chemical properties of the tablet are round in shape, white or almost white in color, with a flat surface, with a chamfer and a notch.
Composition of the drug
active ingredient: allopurinol; 1 tablet contains allopurinol - 100 mg; excipients: lactose monohydrate, microcrystalline cellulose, corn starch, hypromelose, magnesium stearate.
Pharmacotherapeutic group
Antigout drugs. Agents that inhibit the formation of uric acid. ATC code M04AA01.
Indications for use
Allopurinol is indicated to reduce urate/uric acid concentrations in conditions involving accumulation of urate/uric acid deposits (eg, gouty arthritis, cutaneous tophi, nephrolithiasis) or when there is a predictable clinical risk (eg, treatment of a malignant tumor has the potential to 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 overproduction of urates, for example, deficiency of hypoxanthine-guanine phosphoribosyltransferase (including Lesch-Nyhan syndrome), deficiency of glucose-6-phosphatase (including glycogenosis), increased activity of phosphoribosylpyrophosphate synthetase, increased activity of phosphoribosylpyrophosphate amidotransferase, deficiency of adenine phosphoribosyltransferase. Allopurinol is indicated for the treatment of urolithiasis associated with the formation of 2,8-dihydroxyadenine (2,8-DHA) stones as a result of decreased adenine phosphoribosyltransferase activity. Allopurinol is indicated for the treatment of recurrent urolithiasis associated with the formation of mixed calcium-oxalate stones against the background of hyperuricosuria, when increased fluid intake, diet and other methods have been ineffective.
Contraindications
Hypersensitivity to allopurinol or other components of the drug.
Precautionary measures
Hypersensitivity syndrome, SJS and TEN At the first appearance of skin rash or any other signs of hypersensitivity, allopurinol should be discontinued immediately to prevent the development of more serious hypersensitivity reactions (including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)), hypersensitivity syndrome ( drug hypersensitivity syndrome with eosinophilia and systemic symptoms, DRESS). HLA-B*58:01 allele The HLA-B*58:01 allele was identified as a genetic risk factor for the development of allopurinol-associated SJS/TEN‚ (and possibly other serious hypersensitivity reactions) in a retrospective pharmacogenetic case-control study in a Chinese Han population , Taiwanese, Koreans, Japanese and Europeans. The frequency of the HLA-B*58:01 allele can reach 20-30% in the Han Chinese population, and people of African and Indian descent, while only 1-2% of Japanese, northern Europeans and European Americans are carriers of the HLA- allele. B*58:01. Screening for HLA-B*58:01 should be considered before initiating allopurinol treatment in patient subgroups where the prevalence of this allele is known to be high. If patients are carriers of the HLA-B*58:01 allele, then allopurinol should not be prescribed unless there are no other acceptable therapeutic options and the benefits outweigh the potential risks. Patients who do not carry the HLA-B*58:01 allele still have a low risk of developing SJS/TEN. Clinical diagnosis of SJS/TEN and other hypersensitivity reactions is the basis for therapeutic decision making. If such reactions occur at any time during treatment, allopurinol should be discontinued immediately and permanently. Corticosteroids may be effective in treating skin hypersensitivity reactions. Chronic renal failure Patients with chronic renal impairment and concomitant use of diuretics, particularly thiazides, may be at increased risk of developing hypersensitivity reactions, including SJS/TEN, associated with allopurinol. Particular attention is required to identify signs of hypersensitive 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. Hepatic or renal impairment In patients with hepatic or renal impairment, 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 is generally not considered an indication for the use of allopurinol, since an appropriate diet and adequate fluid intake are usually sufficient. Foods high in purines should not be consumed (for example, organ organs: kidney, 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 has completely resolved, 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 large amounts 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 treated with appropriate anti-inflammatory drugs. Xanthine deposition In cases where the intensity of urate formation increases significantly (for example, malignant diseases and their therapy, Lesch-Nyhan syndrome), the absolute concentration of xanthine in the urine can, in rare cases, reach levels that promote xanthine deposition in the urinary tract. This risk can be minimized by adequate hydration to achieve optimal urine dilution by alkalinizing the urine. Blockage of the urinary tract by uric acid kidney stones With adequate therapy with allopurinol, it is possible to dissolve large urate stones in the renal pelvis and 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.
Use during pregnancy or breastfeeding
There is limited data on the safety of allopurinol during pregnancy, although it has been widely used for many years without apparent adverse effects. The use of allopurinol during pregnancy is possible only in the absence of a safer alternative treatment and when the disease itself carries great risks for the mother or unborn child. Allopurinol and oxypurinol are excreted into breast milk. In the breast milk of women taking allopurinol at a dose of 300 mg/day, the concentration of allopurinol reached 1.4 mg/l, oxypurinol - 53.7 mg/l. However, there are no data regarding the effects of allopurinol and its metabolites on the breastfed infant. The drug is not recommended during breastfeeding.
Children
Allopurinol tablets are not used in children under 3 years of age. The ability to influence the reaction rate when driving vehicles or operating other mechanisms. Adverse reactions such as drowsiness, dizziness (vertigo), ataxia, which may affect the ability to drive vehicles OR operate other mechanisms, have been reported with the use of allopurinol. Patients taking allopurinol should not operate vehicles or machinery until they are sure that allopurinol does not adversely affect these abilities.
Interaction with other drugs
Azathioprine, 6-mercaptopurine Azathioprine is metabolized to 6-mercaptopurine, which is inactivated by xanthine oxidase. Since allopurinol inhibits xanthine oxidase, the metabolism of these purine derivatives is slowed, the effects are prolonged, and toxicity increases, so their usual dose should be reduced to 1/4 of the usual dose when used together with allopurinol. Vidarabine (adenine arabinoside) Coadministration of these drugs prolongs the half-life of vidarabine with the risk of increased toxicity. This combination should be used with caution. Salicylates (large doses), uricosurics (eg, sulfinpyrazone, probenecid, benzbromarone) Oxypurinol, the main metabolite of allopurinol, is itself therapeutically active and is excreted by the kidneys in a manner similar to urates. Thus, drugs with uricosuric activity, such as probenecid or large doses of salicylates, may accelerate the excretion of oxypurinol. This may reduce the therapeutic activity of allopurinol, but the significance of this must be assessed on a case-by-case basis. Chlorpropamide If renal function is impaired, the use of allopurinol with chlorpropamide increases the risk of prolonged hypoglycemia, since allopurinol and chlorpropamide may compete for excretion in the renal tubules. Coumarin-type anticoagulants There have been rare reports of increased effects of warfarin and other coumarins when used concomitantly with allopurinol, therefore more frequent monitoring of coagulation parameters in patients receiving these drugs is required. Phenytoin Allopurinol may inhibit the oxidation of phenytoin in the liver; the clinical significance of this interaction has not been established. Theophylline, caffeine Allopurinol in high doses suppresses metabolism and increases plasma concentrations of theophylline and caffeine. At the beginning of treatment with allopurinol or when increasing its dose, the level of theophylline in the blood plasma should be monitored. Ampicillin, amoxicillin The incidence of skin rashes is increased in patients receiving these antibiotics and allopurinol concomitantly, compared with patients who did not receive this combination. The reason for this has not been established. However, patients taking allopurinol should use other antibiotics. Cytostatics (eg, cyclophosphamide doxorubicin, bleomycin, procarbazine, mechlorethamine) Bone marrow suppression with cyclophosphamide and other cytotoxic drugs is increased in patients with neoplastic diseases (other than leukemia) receiving allopurinol. However, in a well-controlled study in patients receiving cyclophosphamide, doxorubicin, bleomycin, procarbazine, and/or mechlorethamine, allopurinol did not increase the toxicity of these cytotoxic drugs. Cyclosporine It is possible to increase the concentration of cyclosporine in the blood plasma with concomitant therapy with allopurinol. The possibility of increased cyclosporine toxicity should be considered if these drugs are taken together. Capecitabine The manufacturer of capecitabine recommends avoiding co-administration with allopurinol. Didanosine In healthy volunteers and HIV-infected patients receiving didanosine, during concomitant therapy with allopurinol (300 mg per day), an approximately 2-fold increase in Cmax and AUC was observed without a change in the terminal half-life. As a rule, the concomitant use of these drugs is not recommended. If concomitant use is unavoidable, a dose reduction of didanosine and careful monitoring of the patient may be necessary. Diuretics An interaction between allopurinol and furosemide has been reported, leading to an increase in serum urate and plasma oxypurinol concentrations. An increased risk of hypersensitivity reactions has been reported when allopurinol is used concomitantly with diuretics, in particular thiazides, especially in patients with impaired renal function. ACE inhibitors An increased risk of hypersensitivity reactions has been reported when allopurinol is used concomitantly with ACE inhibitors, especially in cases of impaired renal function.
Directions for use and dosage
Take after meals, without chewing, with plenty of water. Adults To reduce the risk of adverse reactions, treatment is started with a low dose, for example, 100 mg / day, which is increased only if there is an insufficient response to reduce the concentration of urate in the blood serum. Particular caution should be exercised in patients with 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 disease; 300-600 mg per day for moderate disease; 700-900 mg per day for severe disease. If, when calculating the dose, it is necessary to proceed from 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 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 cancer (especially leukemia) and certain enzymatic disorders (for example, Lesch-Nychen syndrome). Elderly patients In the absence of specific data, the minimum effective dose should be used to ensure a sufficient reduction in serum urate concentrations. Particular attention should be paid to recommendations for selecting the dose of the drug for patients with impaired renal function and certain other conditions (see subsection “Patients with impaired renal function” and section “Precautions”). Patients with Impaired Renal Function Since allopurinol and its metabolites are excreted by the kidneys, impaired renal function may result in retention of the drug and/or its metabolites with subsequent prolongation of their plasma half-life. In case of severe renal failure, it is advisable to use Allopurinol in 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 the blood plasma, then the dose of Allopurinol should be adjusted so as to maintain the level of oxypurinol in the blood plasma below 100 µmol/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 In patients with impaired liver function, reduced doses should be used. In the early stages of therapy, it is recommended to periodically monitor laboratory parameters of liver function. Treatment of conditions with high urate metabolism, for example, neoplasia, Lesch-Nychen 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 and to alkalinize the urine to increase urate/uric acid solubility in urine. Allopurinol dosage should be at the lower end of the recommended dosage range. If renal function is compromised by the development of renal nephropathy OR other renal pathology, then treatment should be continued in accordance with the recommendations presented in the subsection "Patients with impaired renal function." These measures may reduce the risk of xanthine and/or uric acid deposits that complicate 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.
Mode of application
Tablets for oral administration. Allopurinol can be taken once a day after meals. The drug is well tolerated, especially after meals. If the daily dose exceeds 300 mg and gastrointestinal disturbances occur, it is advisable to divide the dose into several doses.
Overdose
It was reported that 22.5 g of allopurinol was taken without adverse reactions. The occurrence of nausea, vomiting, diarrhea, and dizziness was observed in a patient who took allopurinol. To restore the condition, general supportive measures are taken. Massive absorption of allopurinol can lead to 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 excretion of allopurinol and its metabolites. If necessary, hemodialysis is possible.
Side effect
The most common adverse reactions of allopurinol are skin rashes. Adverse effects may vary in frequency depending on the dose received, the disease, and 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 attacks of gout may occur due to the mobilization of uric acid from gouty nodules and other depots. Adverse reactions, information about which is given below, are classified by organs and systems and by the frequency of their occurrence: very often (? 10%); often (?1% and
- Thrombocytopenia, agranulocytosis and aplastic anemia have been reported very rarely, especially in patients with impaired renal and/or hepatic function, highlighting the need for special attention to this group of patients.
- 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 section 4.4). "Skin and subcutaneous tissue").
- Angioimmunoblastic T-cell lymphoma is very rarely diagnosed after lymph node biopsy for generalized lymphadenopathy.
- Nausea and vomiting were reported in early clinical studies. Further observations have shown that these reactions are not a serious problem and can be avoided by taking Allopurinol after meals.
- Liver dysfunction (usually reversible with drug discontinuation) may occur without obvious signs of generalized hypersensitivity reactions.
- Skin reactions are the most common reactions and may occur at any time during treatment. These reactions may be accompanied by itching, the rash may be maculopapular, sometimes pityriasis-like, purpura may develop, and very rarely exfoliative dermatoses such as Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) may develop. The highest risk of developing SJS, TEN or other serious hypersensitivity reactions occurs in the first weeks of treatment. The best results in treating such reactions occur with early diagnosis and immediate discontinuation of any suspected drug. If such reactions develop, Allopurinol should be stopped immediately. If the skin reaction is mild, then after the symptoms disappear, the drug can be re-prescribed at a low dose (for example, 50 mg/day), gradually increasing it if necessary. If the skin rash reappears, the drug should be discontinued permanently, as severe generalized hypersensitivity reactions may occur. If SJS/TEN or other serious hypersensitivity reactions cannot be excluded, treatment with allopurinol should not be restarted 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 time during treatment, allopurinol should be discontinued immediately and permanently.
- Cases of angioedema with and without symptoms of generalized hypersensitivity reactions have been reported.
- Cases of fever with and without symptoms of generalized hypersensitivity reactions have been reported.
The vasculitis and tissue reactions associated with hypersensitivity reactions can have a variety of manifestations, including hepato-splenomegaly, hepatitis, biliary tract disappearance syndrome (destruction and disappearance of the intrahepatic bile ducts), renal failure and, very rarely, seizures. There may be disturbances in other organs (eg, liver, lungs, kidneys, pancreas, myocardium, colon). Acute anaphylactic shock has been reported very rarely. These reactions can occur at any time during treatment and if they occur, allopurinol should be discontinued IMMEDIATELY and PERMANENTLY. Resumption of use of the drug should not be carried out in patients with hypersensitivity syndrome, SJS/TEN. Corticosteroids may be effective in reversing cutaneous hypersensitivity reactions. Generalized hypersensitivity reactions, especially fatal ones, usually developed in patients with impaired renal and/or liver function.
Best before date
5 years Do not use the drug after the expiration date indicated on the package.
Storage conditions
In original packaging at a temperature not exceeding 25°C. Keep out of the reach of children.
Package
10 tablets in a blister made of polyvinyl chloride film and aluminum foil, coated on one side with thermovarnish and printed on the other side. 5 blisters, together with instructions for medical use of the drug or an insert, are placed in a cardboard pack.
Vacation conditions
On prescription.
Side effects of the drug Allopurinol
Treatment with Allopurinol is usually well tolerated by patients. In case of gout, at the beginning of treatment, an exacerbation may occur due to the mobilization of uric acid from gouty nodules and other depots. In some cases, the following are possible: dyspeptic symptoms - nausea, vomiting, epigastric pain, diarrhea; allergic reactions - skin rash, itching, hyperemia, rarely - exfoliative dermatitis, fever, arthralgia; from the blood system - leukopenia, leukocytosis, eosinophilia; from the central nervous system - neuritis, sleep disorders, depression, amnesia.
Special instructions for the use of the drug Allopurinol
It must be taken into account that on the 3rd–4th day after stopping Allopurinol, the indicators of uricosuria and uricemia return to the original, elevated level. Treatment should be long-term; an interval of more than 2-3 days between doses of the drug is undesirable. The drug should be used with caution in cases of mild renal failure (adults in a dose of no more than 0.2 g/day). During the use of Allopurinol, diuresis in adult patients should be maintained at a level of at least 2 l/day. It is necessary to ensure a neutral or slightly alkaline urine reaction to prevent the formation of stones. For this purpose, drugs that alkalize urine are used simultaneously with Allopurinol. To prevent possible attacks of gouty arthritis at the beginning of treatment, you can prescribe NSAIDs or colchicine (adults, 0.5 mg 3 times a day). At the beginning of treatment with Allopurinol, a systematic study of the functional state of the kidneys should be carried out.
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.
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.
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.
