Bionol 300mg 20 Tabs, Alopurinol
BIONOL ® is indicated to reduce the formation of uric acid and urate in conditions in which they have submitted deposits (gouty arthritis, tophi leather, nephrolithiasis) or there is predictable clinical risk, for example, when treatment of certain malignancies can produce acute uric acid nephropathy.
The main clinical entities that can occur in the deposits of uric acid or urates are:
- Drop idiopathic.
- Uric acid lithiasis.
- Acute uric acid nephropathy.
- Neoplastic disease and myeloproliferative disease with high cell turnover, in which they have high levels of urate, either spontaneously or after cytotoxic therapy.
- Overproduction of urate caused by certain enzymatic alterations as hypoxanthine-guanine phosphoribosyl transferase including Lesch-Nyhan syndrome, glucose-6-phosphatase (glycogen storage disease), phosphoribosylpyrophosphate synthetase, adenine phosphoribosylpyrophosphate-amidotransferase and phosphoribosyl transferase.
BIONOL ® is indicated for the management of kidney stones by 2.8-dihydroxyadenine (2,8-DHA) related to deficient activity of adenine phosphoribosyl transferase. Also indicated in the management of recurrent kidney stones mixed calcium oxalate in the presence of hyperuricosuria, when dietary measures have failed and fluid intake.
Pharmacokinetics in Humans:
Allopurinol is active when administered orally and is rapidly absorbed in the upper portion of the gastrointestinal tract.
Detected in blood within 30-60 minutes after administration.
The bioavailability ranges from 67 to 90%.
Peak plasma levels occur 1.5 hours after oral administration, but fall rapidly and barely detectable after 6 hours. Peak plasma levels of oxipurinol usually occur after 3 to 5 hours after oral administration and last longer.
Distribution: Allopurinol binds negligibly to plasma proteins and therefore variations in protein binding do not significantly affect its clearance from plasma.
The apparent volume of distribution is 1.6 l / kg, suggesting extensive uptake by tissues. The highest concentrations are reached in the liver and intestinal mucosa, where there is greater xantinaoxidasa action.
Metabolism: The major metabolite of allopurinol is oxipurinol. Among the other metabolites of allopurinol is allopurinol riboside and oxipurinol--7-riboside.
Approximately 20% of ingested allopurinol is excreted in the feces.
Allopurinol removal occurs primarily through metabolic conversion to oxypurinol, via the aldehyde oxidase and xanthine oxidase, in which less than 10% of the drug is excreted in the urine as unchanged.
Allopurinol has a plasma half-life of approximately 0.5 to 1.5 hours.
Compared with allopurinol, oxipurinol is a less potent inhibitor of xanthine oxidase, but its plasma half-life is much longer. Estimates vary from 13 to 30 hours in man. Therefore, with a single daily dose of allopurinol, remains an effective inhibition of xanthine oxidase during a period of 24 hours. Patients who have normal renal function gradually accumulate oxipurinol until it reaches a plasma concentration of oxypurinol at steady state. By taking allopurinol 300 mg daily, these patients exhibited plasma concentrations of oxipurinol generally 5 to 10 mg / liter.
The oxipurinol is excreted in urine as unchanged, but has an elimination half-lives longer because he suffers tubular reabsorption. The values reported for its elimination half life ranging from 13.6 hours to 29 hours. The huge discrepancies in these values could be explained by variations in study design and / or creatinine clearance in patients.
Pharmacodynamics Allopurinol is an inhibitor of xanthine oxidase.
Allopurinol and its major metabolite oxipurinol, lower uric acid concentrations in plasma and urine, through inhibition of xanthine oxidase, the enzyme that catalyzes the oxidation of xanthine and hypoxanthine to xanthine to acid Uric.
In addition to inhibition of the catabolism of purine, in some patients hyperuricemic, but not all, the de novo biosynthesis of purine undergoes a depression through the feedback of hypoxanthine-guanine phosphoribosyltransferase.
CONTRAINDICATIONS: BIONOL ® should not be administered in patients with known hypersensitivity to allopurinol or any component of the formulation.
PRECAUTIONS: BIONOL® must be removed immediately, when this rash or other evidence of hypersensitivity. Reduced doses should be used in patients with hepatic and / or kidney. Patients treated for hypertension or heart failure with diuretics or ACE inhibitors, may have an injury in renal function, as allopurinol should be used carefully.
Asymptomatic hyperuricemia is not considered an indication for the use of BIONOL ®. Abundant fluids, dietary restrictions and managing the underlying cause may correct this condition.
Acute attacks of gout:
Do not start allopurinol treatment until an acute attack of gout has completely disappeared, and that could precipitate further attacks.
As with uricosuric agents, it is possible to precipitate an acute attack of gouty arthritis in the early stages of treatment with allopurinol.
It is therefore advisable to give prophylaxis with an appropriate anti-inflammatory agent or colchicine, for a few months.
Please refer to the literature for details on proper dosage and warnings, and precautions.
If you develop acute attacks in patients on therapy with allopurinol, treatment should be continued at the same dose level, while concerned with the acute attack any suitable anti-inflammatory agent.
Xanthine deposits: Under conditions in which the rate of formation of urate is extremely increased (as malignant disease and its treatment, Lesch-Nyhan syndrome), urinary concentration of xanthine increases sufficiently to allow the deposit on urinary tract. The risk is minimized by adequate hydration.
Impact of uric acid kidney stones: adequate therapy with BIONOL ® lead to the dissolution of large uric acid kidney stones, with the remote possibility impacted in the ureter.
Effects on ability to drive and use machines: Because some reactions have been reported as drowsiness, dizziness and ataxia in patients treated with allopurinol should be advised caution, especially when driving vehicles, operating machinery or participating in activities dangerous, until they are certain that allopurinol and does not adversely affect performance.
Use in Pregnancy and Lactation
Evidence for BIONOL® safety in pregnancy is insufficient, although it has been used extensively for many years without apparent adverse consequences.
Only be used in pregnancy when no safer alternative and when the disease represents increased risks for mother and fetus.
Breastfeeding: Reports indicate that allopurinol and oxipurinol are excreted in breast milk.
Concentrations of 1.4 mg / l of allopurinol and 53.7 mg / L oxypurinol, were detected in a woman who ingested 300 mg of allopurinol daily.
However, no data on the effects of allopurinol or its metabolites in infants.
There is clinical documentation on this product that can be used as support for determining the frequency of occurrence of adverse effects. It is possible that adverse effects in terms of incidence vary depending on the dose received and if administered in combination with other therapeutic agents.
The categories of frequency allocated to adverse drug effects listed below are estimated for most reactions, no adequate data to calculate the incidence.
The adverse drug events identified through the marketing pharmacovigilance (PMS studies) were considered as rare or very rare. We used the following convention for the classification of frequency:
Very common: = 1/10 (= 10%).
Common: = 1/100 and <1/10 (= 1% and <10%).
Uncommon: = 1/1, 000 and <1/100 (= 0.1% and <1%).
Rare: = 1/10, 000 and <1/1, 000 (= 0.01% and <0.1%).
Very rare: <1/10, 000 (<0.01%).
Adverse events associated with Zyloprim ® in the population treated with this drug are generally rare. The incidence is higher in the presence of liver damage and / or kidney.
Infections and infestations:
Very rare: furunculosis.
Hematological disorders and lymphatic system
Very rare: agranulocytosis, aplastic anemia, thrombocytopenia.
Rarely, there have been case reports of thrombocytopenia, agranulocytosis, aplastic anemia, particularly in individuals with renal and / or liver, which reinforces the need for special precautions for these patient groups.
Immune system disorders:
Uncommon: hypersensitivity reactions.
Very rare: lymphadenopathy angioimmunoblastic.
There are cases of severe hypersensitivity reactions, including skin reactions associated with exfoliation, fever, lymphadenopathy, arthralgia and / or eosinophilia including Stevens-Johnson syndrome and toxic epidermal necrolysis (see Effects on the skin and subcutaneous tissue).
It may manifest cases associated vasculitis and tissue response in several ways, including hepatitis, renal failure and, rarely, seizures. In very rare cases have been reported cases of acute anaphylactic shock. If such reactions occur, they may occur at any time during treatment. BIONOL ® treatment should be discontinued immediately and permanently.
Corticosteroids may be beneficial to mitigate hypersensitivity skin reactions. When there have been generalized hypersensitivity reactions, usually occurred with renal and / or liver are present, particularly when the outcome has been fatal.
Rarely, there have been reports of angioimmunoblastic lymphadenopathy after a biopsy of generalized lymphadenopathy. Appears to be reversible upon discontinuation of treatment with BIONOL ®.
Metabolic and Nutritional:
Very rare: diabetes mellitus, hyperlipidemia.
Very rare: depression.
Nervous system disorders:
Very rare: coma, paralysis, ataxia, neuropathy, paresthesia, drowsiness, headache, dysgeusia.
Very rare: cataract, eye disorders, macular changes.
And labyrinthine hearing disorders:
Very rare: vertigo.
Very Rare: angina pectoris, bradycardia.
Very rare: hypertension.
Uncommon: vomiting, nausea.
Very rare: recurrent hematemesis, steatorrhea, stomatitis, changes in bowel habits.
Uncommon: asymptomatic abnormalities in liver function tests.
Rare: hepatitis (including hepatic necrosis and granulomatosis).
Hepatic dysfunction has been reported without evidence of hypersensitivity symptomatic more widespread.
Alterations of the skin and subcutaneous tissue disorders:
Very rare: angioedema, fixed drug eruption, alopecia, discolored hair.
Skin reactions are the most common effects and can occur at any time during treatment.
They may be pruritic, maculopapular, sometimes scaly, sometimes purpuric and rarely exfoliative.
BIONOL ® therapy should be discontinued immediately if such reactions occur. After recovery from mild reactions, it is possible to restart BIONOL ® therapy, if desired, at reduced dosage (eg, 50 mg / day) gradually increasing it.
If a recurrence of rashes, therapy should be discontinued with BIONOL ® permanently, since there is possibility of occurrence of more severe hypersensitivity reactions (see Immune system disorders).
Have been reported cases of angioedema occur with and without signs and symptoms of a hypersensitivity reaction to allopurinol more widespread.
Renal and urinary disorders:
Very Rare: hematuria, uremia.
Breast abnormalities and reproductive system:
Very rare: male infertility, erectile dysfunction, gynecomastia.
General disorders and administration site conditions:
Very rare: edema, malaise, fatigue, fever.
It is reported that cases of fever occur with and without signs and symptoms of a hypersensitivity reaction to allopurinol more generally (see Immune system disorders).
DRUG INTERACTIONS AND OTHER GENDER:
6-mercaptopurine and azathioprine: Azathioprine is metabolized to 6-mercaptopurine which is inactivated by xanthine oxidase.
When administered orally with BIONOL ® should be administered only 25% of the usual dosage of 6-mercaptopurine or azathioprine, since inhibition of xanthine oxidase prolong their activity.
Vidarabine (adenine arabinoside): Evidence suggests that the presence of allopurinol prolongs the plasma half-life of vidarabine, when used concomitantly, extra vigilance is required to recognize the enhanced toxic effects.
Salicylates and uricosuric agents: oxipurinol The major metabolite of allopurinol, has therapeutic activity itself, is excreted by the kidney in a similar way to urate.
Consequently, drugs with uricosuric activity as probenecid or large doses of salicylate, accelerate the excretion of oxipurinol.
This could decrease the therapeutic activity of BIONOL ®, but the significance of this effect must be evaluated individually.
Chlorpropamide: If given with BIONOL ® when renal function is poor, you can increase and prolong the risk of hypoglycemia, since allopurinol competes in the renal tubular excretion of chlorpropamide.
Coumarin anticoagulants: It has been reported in isolation, increased effects of warfarin and other coumarin anticoagulants when given with allopurinol.
Therefore, all patients receiving anticoagulants should be monitored.
Phenytoin (diphenylhydantoin): Allopurinol may inhibit hepatic oxidation of phenytoin, but have not demonstrated significant clinical effects.
Theophylline has been reported to inhibit the metabolism of theophylline. The mechanism of interaction can be explained by inhibition of xanthine oxidase, involved in the metabolism of theophylline in humans. Theophylline levels should be monitored in patients who initiate or increase treatment with allopurinol.
Ampicillin / amoxicillin: It has been reported a higher incidence of skin rash in patients receiving ampicillin or amoxicillin concurrently with allopurinol compared to patients who have not received any of these drugs. The cause of this association has not been established. However, it is recommended that patients treated with allopurinol is used a different drug to amoxicillin or ampicillin if possible.
Cyclophosphamide, doxorubicin, bleomycin, procarbazine and / or mecloroetamina: Increased bone marrow depression by cyclophosphamide and other cytotoxic agents has been reported in patients with neoplastic disease (as well as leukemias), in the presence of allopurinol.
However, in a well-controlled study patients treated with cyclophosphamide, doxorubicin, bleomycin, procarbazine and / or mecloroetamina (mustine hydrochloride), allopurinol not appear to increase the toxic reaction of these cytotoxic agents.
Cyclosporin: Reports suggest that the plasma concentration of cyclosporine may be increased during concomitant treatment with allopurinol. The possibility of intoxication with cyclosporine should be considered if these drugs are administered simultaneously.
Didanosine: In healthy volunteers and in HIV patients treated with didanosine, plasma Cmax and AUC of didanosine were approximately twice when co-administered treatment with Zyloprim ® (300 mg daily), without affecting the terminal half-life. Therefore, it may be necessary to reduce the dose of didanosine when administered concomitantly with BIONOL ®.
CHANGES IN RESULTS OF LABORATORY TESTS: None reported.
PRECAUTIONS IN RELATION TO EFFECTS OF CARCINOGENESIS, MUTAGENESIS, Impairment of Fertility:
Carcinogenicity: Not found evidence of carcinogenicity in mice or rats treated with allopurinol for 2 years.
Mutagenicity: Cytogenetic studies show that allopurinol did not induce aberrations in human blood cells in vitro at concentrations up to 100 ug / ml and in vivo up to 600 mg / day for an average period of 40 months.
Teratogenicity: A study in mice given intraperitoneal doses of 50 or 100 mg / kg on days 10 or 13 of gestation resulted in fetal abnormalities, however, in a similar study in rats at doses up to 120 mg / kg in day 12 of gestation showed no abnormalities.
Extensive studies with high oral doses of allopurinol to 100 mg / kg / day and 200 mg / day and in rabbits up to 150 mg / kg / day on days 8 to 16 of gestation produced no teratogenic effects.
DOSAGE AND ADMINISTRATION: Oral.
Should avoid splitting the tablets.
Adults: BIONOL ® is started at low doses, 100 mg / day to reduce the risk of adverse reactions. The doses are increased only if the serum urate response is inadequate. Extreme care must be taken if the renal function is impaired (see Dosage in the presence of kidney damage).
The following are suggested dosage schedules: 100 to 200 mg per day in mild cases, 300 to 600 mg per day in moderately severe cases, 700 to 900 mg per day in severe cases.
The dose weight is 2 to 10 mg / kg / day.
Under 15 years: 10 to 20 mg / kg / day, up to 400 mg a day. The use in children is rarely indicated except malignancies (especially leukemia) and certain enzyme disorders such as Lesch-Nyhan syndrome.
Elderly: In the absence of specific data, you should use the lowest dose that produces satisfactory urate reduction.
Particular attention is drawn to the dosage recommendations in renal failure and general precautions.
Renal impairment: Since allopurinol and its metabolites are excreted by the kidneys, impaired renal function may lead to retention of the drug and / or its metabolites with consequent prolongation of plasma half-life.
In severe renal impairment is recommended to use less than 100 mg per day or use 100 mg at intervals greater than one day. If no facility to determine plasma concentrations tions, the dose should be adjusted to maintain plasma levels of oxipurinol below 100 mmol / l (15.2 mg / l).
Also eliminated by renal dialysis in these cases should be considered alternating doses of 200-300 mg immediately after dialysis, without additional post-dose.
Hepatic impairment: reduced doses should be used in patients with poor liver function. It is recommended that liver function tests periodically during the initial stages of therapy.
Treatment of disorders with high production of urate neoplasia Lesch-Nyhan syndrome: It is recommended to correct hyperuricemia and / or hyperuricosuria existing BIONOL ® before starting cytotoxic therapy and alkalinize the urine to increase solubility of uric acid and urate. The dose of BIONOL ® should start in the low range of the recommended dosage schedule.
If urate nephropathy or other pathology has compromised renal function, follow the recommendations in Dosage in renal failure. This will reduce the risk of deposit of xanthines and oxipurinol, which complicate the clinical condition. Interactions
See other gender, and Adverse Effects.
The dosage should be adjusted to maintain adequate levels, serum and urinary urate.
Instructions for Use: BIONOL ® is taken once daily after a meal. It is well tolerated after food. If the daily dose
Name of the medication: BIONOL
Comparative brand name medication: Zyloprin
Active substance: Alopurinol
Concentration: 300 mg
Time release: NoLaboratory:BIORESERCH DE MEXICO
Box with 20 pills
Made in: Mexico