Usual Adult Dose for Wilson's Disease

• Initial dose: 0.75 to 1.5 g orally per day in 4 equal divided doses that results in an initial 24-hour cupriuresis of over 2 mg should be continued for about 3 months
• Maintenance dose: Determined by measurement of urinary copper excretion and determination of free copper in the serum; it is seldom necessary to exceed a dosage of 2 g per day

• This drug should be taken on an empty stomach, 1 hour before or 2 hours after a meal.
• The total daily dose should be divided into 4 equal doses; if 4 equal doses are not feasible, the larger portion should be given at bedtime.
• Patients may require a daily supplement of pyridoxine because this drug increases the requirement for pyridoxine.
• Optimal dosage can be determined by measurement of urinary copper excretion and the determination of free copper in the serum. The urine should be collected in copper-free glassware, and should be quantitatively analyzed for copper before and soon after initiation of therapy.

Usual Adult Dose for Cystinuria

Usual dose: 2 g orally daily with a range of 1 to 4 g per day in 4 equal divided doses

Comments:

• This drug should be taken on an empty stomach, 1 hour before or 2 hours after a meal.
• The total daily dose should be divided into 4 equal doses; if 4 equal doses are not feasible, the larger portion should be given at bedtime.
• Patients should drink about a pint of fluid at bedtime and another pint once during the night when urine is more concentrated and more acid than during the day; the greater the fluid intake, the lower the required dosage of this drug.
• Dosage should be individualized to an amount that limits cystine excretion to 100 to 200 mg per day in those with no history of stones, and below 100 mg per day in those who have had stone formation and/or pain; in determining dosage, the inherent tubular defect, the patient size, age, and rate of growth, diet, and water intake all should be taken into consideration.
• The standard nitroprusside cyanide test may be useful as a qualitative measure of the effective dose.

Usual Adult Dose for Rheumatoid Arthritis

• Initial dose: 125 or 250 mg orally once a day
• Titration: Increase at 1 to 3 month intervals by 125 or 250 mg per day, as response and tolerance indicate
• Maintenance dose: Should be individualized, and may require adjustment during the course of treatment; many patients respond satisfactorily to a dosage within the 500 to 750 mg per day range; changes in maintenance dosage levels may not be reflected clinically or in the erythrocyte sedimentation rate for 2 to 3 months after each dosage adjustment
• Maximum dose: If there is no discernible improvement after 3 to 4 months of therapy with 1 to 1.5 g per day, therapy should be discontinued

• This drug should be taken on an empty stomach, 1 hour before or 2 hours after a meal.
• The total daily dose should be divided into 4 equal doses; if 4 equal doses are not feasible, the larger portion should be given at bedtime.
• The first evidence of a clinical response to this drug in rheumatoid arthritis patients may take 2 to 3 months.
• When therapy has been interrupted because of adverse reactions or other reasons, the drug should be reintroduced cautiously by starting with a lower dosage and increasing slowly.
• During the course of treatment some patients may experience an exacerbation of disease activity following an initial good response; these may be self-limited and can subside within 12 weeks. They are usually controlled by the addition of nonsteroidal anti-inflammatory drugs, and only if the patient has demonstrated a true "escape" phenomenon (as evidenced by failure of the flare to subside within this time period) should an increase in the maintenance dose ordinarily be considered.
• In the rheumatoid patient, migratory polyarthralgia due to this drug is extremely difficult to differentiate from an exacerbation of the rheumatoid arthritis. A substantial reduction in dosage or discontinuing therapy for up to several weeks will usually determine which of these processes is responsible for the arthralgia.

Usual Pediatric Dose for Wilson's Disease

Less than 18 years of age:

• Initial dose: 0.75 to 1.5 g orally per day in 4 equal divided doses that results in an initial 24-hour cupriuresis of over 2 mg should be continued for about 3 months
• Maintenance dose: Determined by measurement of urinary copper excretion and determination of free copper in the serum; it is seldom necessary to exceed a dosage of 2 g per day

• This drug should be taken on an empty stomach, 1 hour before or 2 hours after a meal.
• The total daily dose should be divided into 4 equal doses; if 4 equal doses are not feasible, the larger portion should be given at bedtime.
• Patients may require a daily supplement of pyridoxine because this drug increases the requirement for pyridoxine.
• Optimal dosage can be determined by measurement of urinary copper excretion and the determination of free copper in the serum. The urine should be collected in copper-free glassware, and should be quantitatively analyzed for copper before and soon after initiation of therapy.

Usual Pediatric Dose for Cystinuria

Less than 18 years of age:
Usual dose: 30 mg/kg/day orally

Comments:

• This drug should be taken on an empty stomach, 1 hour before or 2 hours after a meal.
• The total daily dose should be divided into 4 equal doses; if 4 equal doses are not feasible, the larger portion should be given at bedtime.
• Patients should drink copious amounts of fluid.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Wilson's disease:

• In patients who cannot tolerate as much as 1 g per day initially, initiating dosage with 250 mg/day, and increasing gradually to the requisite amount, gives closer control of the effects of the drug and may help to reduce the incidence of adverse reactions.

• Initiating dosage with 250 mg per day, and increasing gradually to the requisite amount, gives closer control of the effects of the drug and may help to reduce the incidence of adverse reactions.
• If adverse reactions necessitate a reduction in dosage, it is important to retain the bedtime dose.

Precautions

US BOXED WARNINGS:

• Physicians planning to use this drug should thoroughly familiarize themselves with its toxicity, special dosage considerations, and therapeutic benefits.
• This drug should never be used casually. Patients should be under the close supervision of the physician.
• Patients should be warned to report promptly any symptoms suggesting toxicity.

Dialysis

Data not available

Other Comments

PENICILLIN ALLERGY:

• Patients who are allergic to penicillin may theoretically have cross-sensitivity to this drug. The possibility of reactions from contamination of this drug by trace amounts of penicillin has been eliminated now that this drug is being produced synthetically rather than as a degradation product of penicillin.

• This drug should be administered on an empty stomach, 1 hour before or 2 hours after a meal.