• Important Safety Information
• Prescribing Information

About Cuprimine^®

Cuprimine^® (Penicillamine) is a chelating agent used for removal of excess copper in patients with Wilson’s disease. It is also used to reduce cystine excretion in cystinuria and to treat patients with severe, active rheumatoid arthritis unresponsive to conventional therapy.¹

In Wilson’s disease

Summary of clinical benefits
In symptomatic patients, Cuprimine^® usually produces marked neurologic improvement, fading of Kayser-Fleischer rings, and gradual amelioration of hepatic dysfunction and psychic disturbances. Noticeable improvement may not occur for one to three months. Clinical experience to date suggests that life is prolonged with this therapy. In asymptomatic patients, signs and symptoms of the disease appear to be prevented indefinitely if daily treatment with Cuprimine^® is continued.1

Dosing considerations
In all patients receiving penicillamine, it is important that Cuprimine^® 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.

For patients with Wilson’s disease, 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 three months. 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. 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.¹

In Cystinuria

Summary of clinical benefits
Conventional treatment is directed at drinking enough fluid to keep urinary cystine diluted enough to prevent stone formation, keeping the urine alkaline enough to dissolve as much cystine as possible, and minimizing cystine production by a diet low in methionine (the major dietary precursor of cystine). When these measures are inadequate to control recurrent stone formation, Cuprimine^® may be used as additional therapy. Also, when patients refuse to adhere to conventional treatment, Cuprimine® may be a useful substitute.

Cuprimine^® reduces excess cystine excretion, at least in part by disulfide interchange between penicillamine and cystine. This results in formation of penicillamine-cysteine disulfide, which is much more soluble than cystine and is excreted readily. Cuprimine is capable of keeping cystine excretion to near normal values. This hinders stone formation and the serious consequences of pyelonephritis and impaired renal function that develop in some patients. In some instances, Cuprimine® has been reported to decrease the size of, and even to dissolve, stones already formed.¹

Dosing considerations
The usual dosage of Cuprimine^® in 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 Cuprimine^®, patients should drink copiously. The greater the fluid intake, the lower the required dosage of Cuprimine®.¹

In Rheumatoid Arthritis

Summary of clinical benefits
Cuprimine appears to suppress disease activity in patients with severe, active rheumatoid arthritis who are unresponsive to conventional therapy. The onset of therapeutic response may not be seen for two or three months. In those patients who respond, the first evidence of suppression of symptoms such as pain, tenderness, and swelling is generally apparent within three months. The optimum duration of therapy has not been determined. If remissions occur, they may last from months to years, but usually require continued treatment.¹

Dosing considerations
The recommended dosage regimen begins with a single daily dose of 125 or 250 mg, which is thereafter increased at one to three month intervals, by 125 mg or 250 mg/day, as patient response and tolerance indicate. The maintenance dosage of Cuprimine® must be individualized, and may require adjustment during the course of treatment. Many patients respond satisfactorily to a dosage within the 500 - 750 mg/day range. Some need less. Some patients will subsequently require an increase in the maintenance dosage to achieve maximal disease suppression.¹

CUPRIMINE Dosing Table

Adapted from Cuprimine package insert. Lawrenceville, NJ: Aton Pharma; 2007.

How to obtain Cuprimine^®

Within the United States, to order product or for customer service please call 1-877-ATON-549 (1-877-286-6549).

Outside of the United States, click here for information regarding product availability.

Important Safety Information
CUPRIMINE^® (Penicillamine) is a chelating agent used in the treatment of Wilson's disease. It is also used to reduce cystine excretion in cystinuria and to treat patients with severe active rheumatoid arthritis unresponsive to conventional therapy. Physicians planning to use penicillamine should thoroughly familiarize themselves with its toxicity, special dosage considerations and therapeutic benefits. Penicillamine should never be used casually. Each patient should remain constantly under the close supervision of the physician. Patients should be warned to report promptly any symptoms suggesting toxicity. Penicillamine can cause fetal harm when administered to a pregnant woman, therefore except for the treatment of Wilson's disease or certain patients with cystinuria, use of penicillamine during pregnancy is contraindicated. Mothers on therapy with penicillamine should not nurse their infants. Patients with a history of penicillamine-related aplastic anemia or agranulocytosis should not be restarted on penicillamine. Because of its potential for causing renal damage, penicillamine should not be administered to rheumatoid arthritis patients with a history or other evidence of renal insufficiency. The use of penicillamine has been associated with fatalities due to certain diseases such as aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture's syndrome, and myasthenia gravis. Leucopenia and thrombocytopenia have been reported to occur up to five percent of patients during penicillamine therapy. Proteinuria and/or hematuria may develop during therapy and may be warning signs of membranous glomerulopathy which can progress to t nephritic syndrome. Intrahepatic cholestasis, toxic hepatitis and obliterative bronchiolitis have been reported. Onset of new neurological symptoms has been reported, or existing neurological symptoms have worsened. Most of the various forms of pemphigus have occurred during treatment with penicillamine. Some patients may experience a drug fever sometimes accompanied with a macular cutaneous eruption. Early and late rashes have occurred. Certain patients may develop a positive antinuclear antibody (ANA) test and some of these may show a lupus erythematosus-like syndrome. Some patients may develop oral ulcerations. Hypogeusia has been reported in some patients. Penicillamine should not be used in patients who are receiving concurrently gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone or phenylbutazone.

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Reference: 1. Cuprimine package insert. Lawrenceville, NJ: Aton Pharma; 2007.