In all patients receiving penicillamine, it is important that Penicillamine be given on an empty stomach, at least one hour before meals or two hours after meals, and at least one hour apart from any other drug, food, or milk. Because penicillamine increases the requirement for pyridoxine, patients may require a daily supplement of pyridoxine.Wilson's Disease: Optimal dosage can be determined by measurement of urinary copper excretion and the determination of free copper in the serum. The urine must be collected in copper-free glassware, and should be quantitatively analyzed for copper before and soon after initiation of therapy with Penicillamine. Determination of 24-hour urinary copper excretion is of greatest value in the first week of therapy with penicillamine. In the absence of any drug reaction, a dose between 0.75 and 1.5 g that results in an initial 24-hour cupriuresis of over 2 mg should be continued for about 3 months, by which time the most reliable method of monitoring maintenance treatment is the determination of free copper in the serum. This equals the difference between quantitatively determined total copper and ceruloplasmin copper. Adequately treated patients will usually have less than 10 mcg free copper/dL of serum. It is seldom necessary to exceed a dosage of 2 g/day. If the patient is intolerant to therapy with Penicillamine, alternative treatment is trientine hydrochloride. In patients who cannot tolerate as much as 1 g/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.Cystinuria: It is recommended that Penicillamine be used along with conventional therapy. By reducing urinary cystine, it decreases crystalluria and stone formation. In some instances, it has been reported to decrease the size of, and even to dissolve, stones already formed.The usual dosage of Penicillamine in the treatment of cystinuria is 2 g/day for adults, with a range of 1 to 4 g/day. For pediatric patients, dosage can be based on 30 mg/kg/day. The total daily amount should be divided into four doses. If four equal doses are not feasible, give the larger portion at bedtime. If adverse reactions necessitate a reduction in dosage, it is important to retain the bedtime dose.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.In addition to taking Penicillamine, patients should drink copiously. It is especially important to 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 Penicillamine.Dosage must be individualized to an amount that limits cystine excretion to 100 to 200 mg/day in those with no history of stones, and below 100 mg/day in those who have had stone formation and/or pain. Thus, in determining dosage, the inherent tubular defect, the patient's size, age, and rate of growth, and his diet and water intake all must be taken into consideration.Rheumatoid Arthritis: The principal rule of treatment with Penicillamine in rheumatoid arthritis is patience. The onset of therapeutic response is typically delayed. Two or three months may be required before the first evidence of a clinical response is noted.When treatment with Penicillamine 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.Initial Therapy- The currently recommended dosage regimen in rheumatoid arthritis begins with a single daily dose of 125 mg or 250 mg, which is thereafter increased at 1- to 3-month intervals, by 125 or 250 mg/day, as patient response and tolerance indicate. If a satisfactoryremission of symptoms is achieved, the dose associated with the remission should be continued. If there is no improvement and there are no signs of potentially serious toxicity after 2 to 3 months of treatment with doses of 500 to 750 mg/day, increases of 250 mg/day at 2- to 3-month intervals may be continued until a satisfactory remission occurs. If there is no discernible improvement after three to four months of treatment with 1000 to 1500 mg of penicillamine/day, it may be assumed the patient will not respond and Penicillamine should be discontinued.
