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BROWSE topics
Gout Treatment / Elevated uric acid levels
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allopurinol (Zyloprim ®):
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CLINICAL PHARMACOLOGY Allopurinol acts on purine catabolism, without disrupting the biosynthesis of purines. It reduces the production of uric acid by inhibiting the biochemical reactions immediately preceding its formation. Allopurinol is a structural analogue of the natural purine base, hypoxanthine. It is an inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid, the end product of purine metabolism in man. Allopurinol is metabolized to the corresponding xanthine analogue, oxipurinol (alloxanthine), which also is an inhibitor of xanthine oxidase. Dosing (Adults): Gout: initially 100mg qd. Increase by 100mg/day q7days, titrate to desired uric acid level (<6 mg/dl). Usual range: (Mild gout): 200-300mg/day. Moderate-severe: 400-600mg/day. (Serum urate concentrations are often reduced more slowly with allopurinol than with uricosuric drugs and minimum concentrations may not be reached for 1-3 weeks. After serum urate concentrations are controlled, it may be possible to reduce dosage; the average adult maintenance dosage is 300 mg daily and the minimum effective dosage is 100-200 mg daily. Allopurinol therapy should be continued indefinitely) Secondary hyperuricemia associated with chemotherapy: Oral: 600-800 mg/day in 2-3 divided doses for prevention of acute uric acid nephropathy for 2-3 days starting 1-2 days before chemotherapy I.V.: 200-400 mg/m2/day (maximum: 600 mg/day) Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. A fluid intake sufficient to yield a daily urinary output of at least 2 L in adults and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable. Recurrent calcium oxalate stones: 200-300 mg/day in single or divided doses Maximum dose/day: 800mg Renal Dosing: [>50 ml/min]: No changes [20-50]: 100-300mg q24h. [10-20]: 100-200mg q24h. [<10]: 100mg q24-48h. [Hemodialysis]: 100mg q24-48h (give dose after dialysis on dialysis days.). |
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colchicine:
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Mechanism of Action The mechanism by which colchicine exerts its beneficial effect in patients with FMF has not been fully elucidated; however, evidence suggests that colchicine may interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1  . Additionally, colchicine disrupts
cytoskeletal functions through inhibition of -tubulin polymerization
into microtubules, and consequently prevents the activation,
degranulation, and migration of neutrophils thought to mediate some gout
symptoms.INDICATIONS AND USAGE 1.1 Gout Flares colchicine tablets are indicated for prophylaxis and the treatment of acute gout flares. Prophylaxis of Gout Flares: colchicine is indicated for prophylaxis of gout flares. Treatment of Gout Flares: colchicine tablets are indicated for treatment of acute gout flares when taken at the first sign of a flare. 1.2 Familial Mediterranean fever (FMF) colchicine tablets are indicated in adults and children 4 years or older for treatment of familial Mediterranean fever (FMF). Dosing (Adults): Gouty arthritis: Adults: Prophylaxis of acute attacks: Oral: 0.6 mg twice daily; initial and/or subsequent dosage may be decreased (ie, 0.6 mg once daily) in patients at risk of toxicity or in those who are intolerant (including weakness, loose stools, or diarrhea); range: 0.6 mg every other day to 0.6 mg 3 times/day Acute attacks: Oral: Initial: 0.6-1.2 mg, followed by 0.6 every 1-2 hours; some clinicians recommend a maximum of 3 doses; more aggressive approaches have recommended a maximum dose of up to 6 mg. Wait at least 3 days before initiating another course of therapy I.V.: Initial: 1-2 mg, then 0.5 mg every 6 hours until response, not to exceed total dose of 4 mg. If pain recurs, it may be necessary to administer additional daily doses. The amount of colchicine administered intravenously in an acute treatment period (generally ~1 week) should not exceed a total dose of 4 mg. Do not administer more colchicine by any route for at least 7 days after a full course of I.V. therapy. Note: Many experts would avoid use because of potential for serious, life-threatening complications. Should not be administered to patients with renal insufficiency, hepatobiliary obstruction, patients >70 years of age, or recent oral colchicine use. Should be reserved for hospitalized patients who are under the care of a physician experienced in the use of intravenous colchicine. ==================== Surgery: Gouty arthritis, prophylaxis of recurrent attacks: Adults: Oral: 0.6 mg/day or every other day; patients who are to undergo surgical procedures may receive 0.6 mg 3 times/day for 3 days before and 3 days after surgery ==================== Primary biliary cirrhosis (unlabeled use): Adults: Oral: 0.6 mg twice daily ==================== Elderly: Reduce maintenance/prophylactic dose by 50% in individuals >70 years ==================== Dosing adjustment in renal impairment: Gouty arthritis, acute attacks: Oral: Specific dosing recommendations not available from the manufacturer: Prophylaxis: Clcr 35-49 mL/minute: 0.6 mg once daily Clcr 10-34 mL/minute: 0.6 mg every 2-3 days Clcr<10 mL/minute: Avoid chronic use of colchicine. Use in serious renal impairment is contraindicated by the manufacturer. Treatment: Clcr<10 mL/minute: Use in serious renal impairment is contraindicated by the manufacturer. If a decision is made to use colchicine, decrease dose by 75%. ==================== Supplied: Injection, solution: 0.5 mg/mL (2 mL) Tablet: 0.6 mg |
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probenecid (Benemid ®):
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CLINICAL PHARMACOLOGY Probenecid is a uricosuric and renal tubular blocking agent. It inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits. Probenecid inhibits the tubular secretion of penicillin and usually increases penicillin plasma levels by any route the antibiotic is given. A 2-fold to 4-fold elevation has been demonstrated for various penicillins. Probenecid has also been reported to inhibit the renal transport of many other compounds including aminohippuric acid (PAH), aminosalicylic acid (PAS), indomethacin, sodium iodomethamate and related iodinated organic acids, 17-ketosteroids, pantothenic acid, phenolsulfonphthalein (PSP), sulfonamides, and sulfonylureas. Probenecid decreases both hepatic and renal excretion of sulfobromophthalein (BSP). The tubular reabsorption of phosphorus is inhibited in hypoparathyroid but not in euparathyroid individuals. Probenecid does not influence plasma concentrations of salicylates, nor the excretion of streptomycin, chloramphenicol, chlortetracycline, oxytetracycline, or neomycin. INDICATIONS AND USAGE For treatment of the hyperuricemia associated with gout and gouty arthritis. As an adjuvant to therapy with penicillin or with ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whatever route the antibiotic is given. Dosing (Adults): Oral: Hyperuricemia with gout: 250 mg twice daily for one week; increase to 250-500 mg/day; may increase by 500 mg/month, if needed, to maximum of 2-3 g/day (dosages may be increased by 500 mg every 6 months if serum urate concentrations are controlled) Prolong penicillin serum levels: 500 mg 4 times/day Gonorrhea: 1 g 30 minutes before penicillin, ampicillin, procaine, or amoxicillin Pelvic inflammatory disease: Cefoxitin 2 g I.M. plus probenecid 1 g orally as a single dose Neurosyphilis: Aqueous procaine penicillin 2.4 million units/day I.M. plus probenecid 500 mg 4 times/day for 10-14 days Dosing adjustment in renal impairment: Clcr<50 mL/minute: Avoid use Supplied Tablet: 500 mg |
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Rasburicase
(Elitek®):
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Mechanism of Action In humans, uric acid is the final step in the catabolic pathway of purines. Rasburicase catalyzes enzymatic oxidation of poorly soluble uric acid into an inactive and more soluble metabolite (allantoin). INDICATIONS AND USAGE Elitek® is indicated for the initial management of plasma uric acid levels in pediatric and adult patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anti-cancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid. Limitation of use: Elitek is indicated only for a single course of treatment Recommended dose: 0.15 or 0.20 mg/kg as a single daily dose for 5 days. Because the safety and effectiveness of other schedules have not been established, dosing beyond 5 days or administration of more than one course is not recommended. Chemotherapy should be initiated 4 to 24 hours after the first dose of rasburicase. Rasburicase should be administered as an intravenous infusion over 30 minutes (NEVER as a bolus infusion). Rasburicase is contraindicated in individuals deficient in glucose-6-phosphate dehydrogenase (G6PD). Supplied Injection, powder for reconstitution: 1.5 mg [packaged with three 1 mL ampules of diluent] |
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sulfinpyrazone (Anturane ®)
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Uricosuric agent. CLINICAL PHARMACOLOGY Its pharmacologic activity is the potentiation of the urinary excretion of uric acid. It is useful for reducing the blood urate levels in patients with chronic tophaceous gout and acute intermittent gout, and for promoting the resorption of tophi. INDICATIONS Anturane is indicated for the treatment of: 1] Chronic gouty arthritis 2] Intermittent gouty arthritis CONTRAINDICATIONS Patients with an active peptic ulcer or symptoms of gastrointestinal inflammation or ulceration should not receive the drug. The drug is contraindicated in patients with a history or the presence of: Hypersensitivity to phenylbutazone or other pyrazoles Blood dyscrasias WARNINGS Studies on the teratogenicity of pyrazole compounds in animals have yielded inconclusive results. Up to the present time, however, there have been no reported cases of human congenital malformation proved to be due to the use of the drug. It is suggested that Anturane be used with caution in pregnant women, weighing the potential risks against the possible benefits. Dosage Gout Adults: OInitially: 100-200mg orally twice daily with meals. Maintenance: 200mg orally twice daily with meals. Maximum daily dose: 800mg Renal Dosing Do not use if crcl<50 ml/min. Supplied Tablet: 100 mg |
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Principles of treatment: |
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Do not treat asymptomatic hyperuricemia. Also, do not treat
hyperuricemia during acute gouty arthritis attack. Treat patients with
tophi or polyarticular gout. Probably treat patients with recurrent
attacks and serum uric acid >9 mg/dl--Start with low dose and gradually
increase (titrate to serum uric acid) over weeks to months. Monitor
serum uric acid and aim for uric acid <6.0 mg/dl (or <5.0 with tophi).
Use concomitant colchicine prophylaxis until uric acid has been at
desired level for some months and no recent gouty attacks have occurred
(6-12 months). Use uricosuric drugs (probenecid, sulfinpyrazone) when
possible because of low toxicity. Use allopurinol in patients with renal
calculi, renal insufficiency, concomitant diuretic therapy, cyclosporine
therapy, urate overproduction. Things to Remember 1. Uric acid may be low, normal, or high during an attack. 2. Low dose colchicine should be started when initiating uric acid lowering drugs. 3. Do not initiate uric acid altering drugs during an acute attack. Wait until attack fully resolved. 4. Indications for Allopurinol use (stated above) 5. Place patient on a low purine diet (seafood, organ meats, spinach, asparagus), alcohol abstinence, weight loss if obese. |
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