Kuprenil Uses

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What is Kuprenil?

Kuprenil is a chelating (KEE-late-ing) agent that binds to excess copper and removes it from the blood stream. In certain conditions, excess copper can build up in the blood stream, leading to tissue damage throughout the body.

Kuprenil is used to remove excess copper in people with an inherited condition called Wilson's disease.

Kuprenil is also used to reduce urine levels of an amino acid called cystine, which can cause stones to form in the kidneys and bladder in people with an inherited condition called cystinuria.

Kuprenil is also used to treat severe rheumatoid arthritis after other medicines have been tried without success. This medicine is not approved to treat juvenile rheumatoid arthritis.

Kuprenil may also be used for purposes not listed in this medication guide.

Kuprenil indications


Kuprenil is indicated in the treatment of Wilson's disease, cystinuria, and in patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy. Available evidence suggests that Kuprenil is not of value in ankylosing spondylitis.

Wilson's Disease

Wilson's disease (hepatolenticular degeneration) occurs in individuals who have inherited an autosomal recessive defect that leads to an accumulation of copper far in excess of metabolic requirements. The excess copper is deposited in several organs and tissues, and eventually produces pathological effects primarily in the liver, where damage progresses to postnecrotic cirrhosis, and in the brain, where degeneration is widespread. Copper is also deposited as characteristic, asymptomatic, golden-brown Kayser-Fleischer rings in the corneas of all patients with cerebral symptomatology and some patients who are either asymptomatic or manifest only hepatic symptomatology.

Two types of patients require treatment for Wilson's disease: (1) the symptomatic, and (2) the asymptomatic in whom it can be assumed the disease will develop in the future if the patient is not treated.

The diagnosis, if suspected on the basis of family or individual history or physical examination, can be confirmed if the plasma copper-protein ceruloplasmin** is < 20 mg/dL and either a quantitative determination in a liver biopsy specimen shows an abnormally high concentration of copper ( > 250 mcg/g dry weight) or Kayser-Fleischer rings are present.

Treatment has two objectives:

The first objective is attained by a daily diet that contains no more than one or two milligrams of copper. Such a diet should exclude, most importantly, chocolate, nuts, shellfish, mushrooms, liver, molasses, broccoli, and cereals and dietary supplements enriched with copper, and be composed to as great an extent as possible of foods with a low copper content. Distilled or demineralized water should be used if the patient's drinking water contains more than 0.1 mg of copper per liter.

For the second objective, a copper chelating agent is used.

In symptomatic patients this treatment usually produces marked neurologic improvement, fading of Kayser-Fleischer rings, and gradual amelioration of hepatic dysfunction and psychic disturbances.

Clinical experience to date suggests that life is prolonged with the above regimen.

Noticeable improvement may not occur for one to three months. Occasionally, neurologic symptoms become worse during initiation of therapy with Kuprenil. Despite this, the drug should not be withdrawn. Temporary interruption carries an increased risk of developing a sensitivity reaction upon resumption of therapy, although it may result in clinical improvement of neurological symptoms. If the neurological symptoms and signs continue to worsen for a month after the initiation of Kuprenil therapy, several short courses of treatment with 2,3 - dimercaprol (BAL) while continuing Kuprenil may be considered.

Treatment of asymptomatic patients has been carried out for over thirty years. Symptoms and signs of the disease appear to be prevented indefinitely if daily treatment with Kuprenil is continued.


Cystinuria is characterized by excessive urinary excretion of the dibasic amino acids, arginine, lysine, ornithine, and cystine, and the mixed disulfide of cysteine and homocysteine. The metabolic defect that leads to cystinuria is inherited as an autosomal, recessive trait. Metabolism of the affected amino acids is influenced by at least two abnormal factors: (1) defective gastrointestinal absorption and (2) renal tubular dysfunction.

Arginine, lysine, ornithine, and cysteine are soluble substances, readily excreted. There is no apparent pathology connected with their excretion in excessive quantities.

Cystine, however, is so slightly soluble at the usual range of urinary pH that it is not excreted readily,and so crystallizes and forms stones in the urinary tract. Stone formation is the only known pathology in cystinuria.

Normal daily output of cystine is 40 to 80 mg. In cystinuria, output is greatly increased and may exceed 1 g/day. At 500 to 600 mg/day, stone formation is almost certain. When it is more than 300 mg/day, treatment is indicated.

Conventional treatment is directed at keeping 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). Patients must drink enough fluid to keep urine specific gravity below 1.010, take enough alkali to keep urinary pH at 7.5 to 8, and maintain a diet low in methionine. This diet is not recommended in growing children and probably is contraindicated in pregnancy because of its low protein content.

When these measures are inadequate to control recurrent stone formation, Kuprenil may be used as additional therapy, and when patients refuse to adhere to conventional treatment, Kuprenil may be a useful substitute. It is capable of keeping cystine excretion to near normal values, thereby hindering stone formation and the serious consequences of pyelonephritis and impaired renal function that develop in some patients.

Bartter and colleagues depict the process by which Kuprenil interacts with cystine to form Kuprenil-cysteine mixed disulfide as:

CSSC = cystine

CS' = deprotonated cysteine

PSSP = Kuprenil disulfide

PS' = deprotonated Kuprenil sulfhydryl

CSSP = Kuprenil-cysteine mixed disulfide

In this process, it is assumed that the deprotonated form of Kuprenil, PS', is the active factor in bringing about the disulfide interchange.

Rheumatoid Arthritis

Because Kuprenil can cause severe adverse reactions, its use in rheumatoid arthritis should be restricted to patients who have severe, active disease and who have failed to respond to an adequate trial of conventional therapy. Even then, benefit-to-risk ratio should be carefully considered. Other measures, such as rest, physiotherapy, salicylates, and corticosteroids should be used, when indicated, in conjunction with Kuprenil.

How should I use Kuprenil?

Use Kuprenil as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Ask your health care provider any questions you may have about how to use Kuprenil.

Uses of Kuprenil in details


Treatment of rheumatoid arthritis, Wilson's disease and prevention of cystine kidney stones.

Kuprenil description

Kuprenil is a pharmaceutical of the chelator class. The pharmaceutical form is D-Kuprenil, as L-Kuprenil is toxic (it inhibits the action of pyridoxine). It is an α-amino acid metabolite of penicillin, although it has no antibiotic properties.

Kuprenil dosage

Kuprenil Dosage

Generic name: Kuprenil 250mg

Dosage form: tablet

The information at Drugs.com is not a substitute for medical advice. Always consult your doctor or pharmacist.

In all patients receiving Kuprenil, it is important that Kuprenil 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 Kuprenil 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 Kuprenil.

Determination of 24-hour urinary copper excretions is of greatest value in the first week of therapy with Kuprenil. 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, 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 Kuprenil, 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 Kuprenil 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 Kuprenil 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 Kuprenil, 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 Kuprenil.

Dosage must be individualized to an amount that limits cystine excretion to 100-200 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 deter-mining 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.

The standard nitroprusside cyanide test has been reported useful as a qualitative measure of the effective dose*:

* Lotz, M., Potts, J.T. and Bartter, F.C.: BritMed J 2: 521, August 28, 1965 (in Medical Memoranda).

Add 2 mL of freshly prepared 5 percent sodium cyanide to 5 mL of a 24-hour aliquot of protein-free urine and let stand ten minutes. Add 5 drops of freshly prepared 5 percent sodium nitroprusside and mix. Cystine will turn the mixture magenta. If the result is negative, it can be assumed that cystine excretion is less than 100 mg/g creatinine.

Although Kuprenil is rarely excreted unchanged, it also will turn the mixture magenta. If there is any question as to which substance is causing the reaction, a ferric chloride test can be done to eliminate doubt: Add 3 percent ferric chloride dropwise to the urine. Kuprenil will turn the urine an immediate and quickly fading blue. Cystine will not produce any change in appearance.

Rheumatoid Arthritis - The principal rule of treatment with Kuprenil 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 Kuprenil 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 one to three month intervals, by 125 mg or 250 mg/day, as patient response and tolerance indicate. If a satisfactory remission 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 two to three months of treatment with doses of 500-750 mg/day, increases of 250 mg/day at two to three month intervals may be continued until a satisfactory remission occurs or signs of toxicity develop. If there is no discernible improvement after three to four months of treatment with 1000 to 1500 mg of Kuprenil/day, it may be assumed the patient will not respond and Kuprenil should be discontinued.

Maintenance Therapy - The maintenance dosage of Kuprenil 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.

Changes in maintenance dosage levels may not be reflected clinically or in the erythrocyte sedimentation rate for two to three months after each dosage adjustment.

Some patients will subsequently require an increase in the maintenance dosage to achieve maximal disease suppression. In those patients who do respond, but who evidence incomplete suppression of their disease after the first six to nine months of treatment, the daily dosage of Kuprenil may be increased by 125 mg or 250 mg/day at three-month intervals. It is unusual in current practice to employ a dosage in excess of 1 g/day, but up to 1.5 g/day has sometimes been required.

Management of Exacerbations - 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 twelve 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 Kuprenil is extremely difficult to differentiate from an exacerbation of the rheumatoid arthritis. Discontinuance or a substantial reduction in the dosage of Kuprenil for up to several weeks will usually determine which of these processes is responsible for the arthralgia.

Duration of Therapy - The optimum duration of Kuprenil therapy in rheumatoid arthritis has not been determined. If the patient has been in remission for six months or more, a gradual, stepwise dosage reduction in decrements of 125 mg or 250 mg/day at approximately three month intervals may be attempted.

Concomitant Drug Therapy - Kuprenil should not be used in patients who are receiving gold therapy, anti-malarial or cytotoxic drugs, oxyphenbutazone, or phenylbutazone. Other measures, such as salicylates, other nonsteroidal anti-inflammatory drugs or systemic corticosteroids may be continued when Kuprenil is initiated. After improvement commences, analgesic and anti-inflammatory drugs may be slowly discontinued as symptoms permit. Steroid withdrawal must be done gradually, and many months of Kuprenil treatment may be required before steroids can be completely eliminated.

Dosage Frequency - Based on clinical experience, dosages up to 500 mg/day can be given as a single daily dose. Dosages in excess of 500 mg/day should be administered in divided doses.

More about Kuprenil (Kuprenil)

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Kuprenil interactions

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What other drugs will affect Kuprenil?


Digoxin: Kuprenil may decrease the serum concentration of Digoxin. Monitor therapy

Gold Sodium Thiomalate: May enhance the adverse/toxic effect of Kuprenil. Specifically, this combination may increase the risk for serious hematologic and/or renal adverse reactions. Avoid combination

Polyvalent Cation Containing Products: May decrease the serum concentration of Kuprenil. Management: Separate the administration of Kuprenil and oral polyvalent cation containing products by at least 1 hour. Consider therapy modification

Kuprenil side effects

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What are the possible side effects of Kuprenil?

Applies to Kuprenil: oral capsule, oral tablet

Along with its needed effects, Kuprenil (the active ingredient contained in Kuprenil) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur while taking Kuprenil:

More Common

Less Common


Some side effects of Kuprenil may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

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Kuprenil contraindications

See also:
What is the most important information I should know about Kuprenil?


Except for the treatment of Wilson’s disease or certain patients with cystinuria, use of Kuprenil during pregnancy is contraindicated.

Although breast milk studies have not been reported in animals or humans, mothers on therapy with Kuprenil should not nurse their infants.

Patients with a history of Kuprenil-related aplastic anemia or agranulocytosis should not be restarted on Kuprenil.

Because of its potential for causing renal damage, Kuprenil should not be administered to rheumatoid arthritis patients with a history or other evidence of renal insufficiency.

Active ingredient matches for Kuprenil:


List of Kuprenil substitutes (brand and generic names)

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Unit description / dosage (Manufacturer)Price, USD
Tablet, Film-Coated; Oral; Penicillamine 150 mg (Abbott)
Tablet, Film-Coated; Oral; Penicillamine 300 mg (Abbott)
Tablet, Enteric Coated; Oral; Penicillamine 150 mg (Abbott)
Tablet, Enteric Coated; Oral; Penicillamine 300 mg (Abbott)
Metalcaptase 150 mg (Abbott)
Metalcaptase 300 mg x 20's (Abbott)
250 mg x 10's (Medi Globe)$ 1.81
PENAMINE cap 250 mg x 10's (Medi Globe)$ 1.81
Penicillamine/ d- powder$ 8.88
Cuprimine 250 mg capsule$ 5.63
Depen 250 mg titratab$ 4.73
Penicillamine powder$ 2.81
Penicillamine/ d- powder$ 8.88
Cuprimine 250 mg capsule$ 5.63
Depen 250 mg titratab$ 4.73
Penicillamine powder$ 2.81
Penicillamine/ d- powder$ 8.88
Cuprimine 250 mg capsule$ 5.63
Depen 250 mg titratab$ 4.73
Penicillamine powder$ 2.81
Penicitin 250mg CAP / 10 (Samarth)$ 1.78
PENICITIN 250 MG CAPSULE 1 strip / 10 capsules each (Samarth)$ 1.75
PENICITIN cap 250 mg x 10's (Samarth)$ 1.66
Penicitin 250mg Capsule (Samarth)$ 0.17
Tablet, Film-Coated; Oral; Penicillamine 300 mg (Asta medica)


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Information checked by Dr. Sachin Kumar, MD Pharmacology

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