Penicillamine

Name: Penicillamine

Warnings

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.

Because of the potential for serious hematological and renal adverse reactions to occur at any time, routine urinalysis, white and differential blood cell count, hemoglobin determination, and direct platelet count must be done twice weekly, together with monitoring of the patient's skin, lymph nodes and body temperature, during the first month of therapy, every two weeks for the next five months, and monthly thereafter. Patients should be instructed to report promptly the development of signs and symptoms of granulocytopenia and/or thrombocytopenia such as fever, sore throat, chills, bruising or bleeding. The above laboratory studies should then be promptly repeated.

Leukopenia and thrombocytopenia have been reported to occur in up to five percent of patients during penicillamine therapy. Leukopenia is of the granulocytic series and may or may not be associated with an increase in eosinophils. A confirmed reduction in WBC below 3500/mm³ mandates discontinuance of penicillamine therapy. Thrombocytopenia may be on an idiosyncratic basis, with decreased or absent megakaryocytes in the marrow, when it is part of an aplastic anemia. In other cases the thrombocytopenia is presumably on an immune basis since the number of megakaryocytes in the marrow has been reported to be normal or sometimes increased. The development of a platelet count below 100,000/mm³, even in the absence of clinical bleeding, requires at least temporary cessation of penicillamine therapy. A progressive fall in either platelet count or WBC in three successive determinations, even though values are still within the normal range, likewise requires at least temporary cessation.

Proteinuria and/or hematuria may develop during therapy and may be warning signs of membranous glomerulopathy which can progress to a nephrotic syndrome. Close observation of these patients is essential. In some patients the proteinuria disappears with continued therapy; in others, penicillamine must be discontinued. When a patient develops proteinuria or hematuria the physician must ascertain whether it is a sign of drug-induced glomerulopathy or is unrelated to penicillamine.

Rheumatoid arthritis patients who develop moderate degrees of proteinuria may be continued cautiously on penicillamine therapy, provided that quantitative 24-hour urinary protein determinations are obtained at intervals of one to two weeks. Penicillamine dosage should not be increased under these circumstances. Proteinuria which exceeds 1 g/24 hours, or proteinuria which is progressively increasing, requires either discontinuance of the drug or a reduction in the dosage. In some patients, proteinuria has been reported to clear following reduction in dosage.

In rheumatoid arthritis patients penicillamine should be discontinued if unexplained gross hematuria or persistent microscopic hematuria develops.

In patients with Wilson's disease or cystinuria the risks of continued penicillamine therapy in patients manifesting potentially serious urinary abnormalities must be weighed against the expected therapeutic benefits.

When penicillamine is used in cystinuria, an annual x-ray for renal stones is advised. Cystine stones form rapidly, sometimes in six months. Up to one year or more may be required for any urinary abnormalities to disappear after penicillamine has been discontinued.

Because of rare reports of intrahepatic cholestasis and toxic hepatitis, liver function tests are recommended every six months for the duration of therapy. In Wilson's disease, these are recommended every three months, at least during the first year of treatment.

Goodpasture's syndrome has occurred rarely. The development of abnormal urinary findings associated with hemoptysis and pulmonary infiltrates on x-ray requires immediate cessation of penicillamine.

Obliterative bronchiolitis has been reported rarely. The patient should be cautioned to report immediately pulmonary symptoms such as exertional dyspnea, unexplained cough or wheezing. Pulmonary function studies should be considered at that time.

Onset of new neurological symptoms has been reported with CUPRIMINE (see ADVERSE REACTIONS). Occasionally, neurological symptoms become worse during initiation of therapy with CUPRIMINE (see INDICATIONS). Myasthenic syndrome sometimes progressing to myasthenia gravis has been reported. Ptosis and diplopia, with weakness of the extraocular muscles, are often early signs of myasthenia. In the majority of cases, symptoms of myasthenia have receded after withdrawal of penicillamine.

Most of the various forms of pemphigus have occurred during treatment with penicillamine. Pemphigus vulgaris and pemphigus foliaceus are reported most frequently, usually as a late complication of therapy. The seborrhea-like characteristics of pemphigus foliaceus may obscure an early diagnosis. When pemphigus is suspected, CUPRIMINE should be discontinued. Treatment has consisted of high doses of corticosteroids alone or, in some cases, concomitantly with an immunosuppressant. Treatment may be required for only a few weeks or months, but may need to be continued for more than a year.

Once instituted for Wilson's disease or cystinuria, treatment with penicillamine should, as a rule, be continued on a daily basis. Interruptions for even a few days have been followed by sensitivity reactions after reinstitution of therapy.

Pregnancy Category D

Penicillamine can cause fetal harm when administered to a pregnant woman. Penicillamine has been shown to be teratogenic in rats when given in doses 6 times higher than the highest dose recommended for human use. Skeletal defects, cleft palates and fetal toxicity (resorptions) have been reported.

There are no controlled studies on the use of penicillamine in pregnant women. Although normal outcomes have been reported, characteristic congenital cutis laxa and associated birth defects have been reported in infants born of mothers who received therapy with penicillamine during pregnancy. Penicillamine should be used in women of childbearing potential only when the expected benefits outweigh the possible hazards. Women on therapy with penicillamine who are of childbearing potential should be apprised of this risk, advised to report promptly any missed menstrual periods or other indications of possible pregnancy, and followed closely for early recognition of pregnancy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Wilson's Disease

Reported experience*** shows that continued treatment with penicillamine throughout pregnancy protects the mother against relapse of the Wilson's disease, and that discontinuation of penicillamine has deleterious effects on the mother, which may be fatal.

If penicillamine is administered during pregnancy to patients with Wilson's disease, it is recommended that the daily dosage be limited to 750 mg. If cesarean section is planned the daily dose should be reduced to 250 mg, but not lower, for the last six weeks of pregnancy and postoperatively until wound healing is complete.

Cystinuria

If possible, penicillamine should not be given during pregnancy to women with cystinuria (see CONTRAINDICATIONS). There are reports of women with cystinuria on therapy with penicillamine who gave birth to infants with generalized connective tissue defects who died following abdominal surgery. If stones continue to form in these patients, the benefits of therapy to the mother must be evaluated against the risk to the fetus.

Rheumatoid Arthritis

Penicillamine should not be administered to rheumatoid arthritis patients who are pregnant (see CONTRAINDICATIONS) and should be discontinued promptly in patients in whom pregnancy is suspected or diagnosed.

There is a report that a woman with rheumatoid arthritis treated with less than one gram a day of penicillamine during pregnancy gave birth (cesarean delivery) to an infant with growth retardation, flattened face with broad nasal bridge, low set ears, short neck with loose skin folds, and unusually lax body skin.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Penicillamine Dosage and Administration

General

  • Individualize dosage according to the condition being treated and patient response.a b c

  • When used for cystinuria, high fluid intake (e.g., 500 mL of water at bedtime and again during the night) needed.a b c The greater the fluid intake, the lower the penicillamine dosage required.a b c

Administration

Oral Administration

Administer orally on an empty stomach (i.e., at least 1 hour before or 2 hours after meals, and at least 1 hour apart from any other drug, food, or milk).a b c Administer the last dose of the day ≥3 hours after the evening meal.c Administration on an empty stomach ensures maximum absorption and reduces the potential for inactivation of penicillamine by metals in the GI tract.a b

If used in individuals who cannot swallow capsules, contents may be administered in 15–30 mL of chilled pureed fruit or fruit juice.c

When used for rheumatoid arthritis, administer dosages >500 mg daily in divided doses.a b c

Dosage

Pediatric Patients

Wilson’s Disease Oral

Optimal dosage determined by measuring urinary copper excretion and/or serum free copper concentrations.a b c

20 mg/kg daily given in divided doses.c

Cystinuria Oral

Individualize dosage based on urinary cystine excretion.a b c

30 mg/kg daily given in 4 equal doses.a b c If 4 equal doses are not feasible, give larger dose at bedtime.a b c If dosage reduced because of adverse effects, retain bedtime dose.a b c

Lead Poisoning† Oral

20–30 mg/kg daily has been recommended.c

Adults

Wilson’s Disease Oral

Optimal dosage determined by measuring urinary copper excretion and/or serum free copper concentrations.a b c

Initially, 250 mg 4 times daily.a b c For patients who do not tolerate an initial dosage of 1 g daily, initiate with 250 mg daily and gradually increase dosage.a b c

If tolerated, a dosage of 0.75–1.5 g daily should be continued for 3 months; this dosage produces an initial 24-hour cupruresis of >2 mg.a b c Subsequent dosage based on serum free copper concentrations.a b c

Dosages >2 g daily are seldom necessary.a b c

Cystinuria Oral

Individualize dosage based on urinary cystine excretion.a b c

Initiate with 250 mg daily and gradually increase dosage to provide close control and minimize adverse reactions.a b c

Usual dosage is 2 g daily given in 4 equal doses; range is 1–4 g daily.a b c If 4 equal doses are not feasible, give larger dose at bedtime.a b c If dosage reduced because of adverse effects, retain bedtime dose.a b c

Rheumatoid Arthritis Initial Therapy Oral

Initially, 125–250 mg daily; increase by 125–250 mg daily at 1–3 month intervals as patient response and tolerance allow.a b c Many patients achieve remission with dosage of 500–750 mg daily.c

If remission is achieved, continue dosage; if no improvement and no signs of serious toxicity noted with 500–750 mg daily, increase by 250 mg daily at 2–3 month intervals until remission occurs or toxicity develops.a b c

Discontinue penicillamine if improvement not observed after 3–4 months of treatment with 1–1.5 g daily.a b c

Maintenance Therapy Oral

Usual dosage 500–750 mg daily; in patients who respond, but have incomplete suppression of disease after the first 6–9 months of therapy, increase daily dosage by 125–250 mg daily at 3 month intervals to a maximum of 1–1.5 g daily.a b c

Optimum duration of therapy not established; attempt to reduce dosage by 125–250 mg daily at 3 month intervals in patients with remission of symptoms ≥6 months, a b c

Exacerbation Therapy Oral

If exacerbation does not subside within 3 months, consider increasing penicillamine dosage.a b c

Prescribing Limits

Adults

Wilson’s Disease Oral

Maximum 2 g daily.a b c

Rheumatoid Arthritis Oral

Maximum 1 g daily; occasionally 1.5 g daily required.a b c

Special Populations

Pregnancy

If penicillamine is used in pregnant women with Wilson's disease, the manufacturers recommend a maximum dosage of 0.75–1 g daily.a b If cesarean section is planned, the recommended dosage is 250 mg daily during the last 6 weeks of pregnancy; this dosage is continued postoperatively until wound healing is complete.a b (See Contraindications and Mucocutaneous Effects under Cautions.)

Surgical Candidates

Reduce dosage to 250 mg daily in patients considering surgery.a b Do not reinitiate full dosage until wound healing is complete.a b (See Contraindications and Mucocutaneous Effects under Cautions.)

Advice to Patients

  • Importance of advising patients to seek immediate medical attention if signs and symptoms of toxicity (e.g., fever, sore throat, chills, bruising, bleeding) develop.a b

  • Importance of taking penicillamine on an empty stomach (at least 1 hour before or 2 hours after meals, and at least 1 hour apart from any other drug, food, or milk).a b c

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses.a b

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; apprise women of potential risks to fetus.a b Importance of women of childbearing potential informing clinician of missed period(s).a b

  • Importance of informing patients of other important precautionary information.a b (See Cautions.)

Precautions While Using penicillamine

Your doctor should check your progress at regular visits to make sure that penicillamine does not cause unwanted effects.

Before having any kind of surgery (including dental surgery), tell the medical doctor or dentist in charge that you are taking penicillamine.

Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.

Do not take iron preparations or vitamin preparations containing iron without checking with your healthcare provider. If your doctor tells you to take iron preparations, or vitamin preparations containing iron, do not take them within 2 hours of the time you take penicillamine. Taking the two medicines too close together may keep the penicillamine from working properly.

Tell your doctor right away if you get a fever, sore throat, chills, bruising, or bleeding. These may be symptoms of a serious blood problem.

Tell your doctor right away if you have trouble breathing, noisy breathing, or an unexplained cough. These may be symptoms of a serious lung problem.

penicillamine Side Effects

Along with its needed effects, a medicine 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:

More common
  • Fever
  • joint pain
  • lesions on the face, neck, scalp, and/or trunk
  • skin rash, hives, or itching
  • swollen and/or painful glands
  • ulcers, sores, or white spots on lips or in mouth
Less common
  • Bloody or cloudy urine
  • shortness of breath, troubled breathing, tightness in chest, or wheezing
  • sore throat and fever with or without chills
  • swelling of face, feet, or lower legs
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • weight gain
Rare
  • Abdominal or stomach pain (severe)
  • blisters on skin
  • bloody or black, tarry stools
  • chest pain
  • coughing or hoarseness
  • dark urine
  • difficulty in breathing, chewing, talking, or swallowing
  • eye pain, blurred or double vision, or any change in vision
  • general feeling of discomfort or illness or weakness
  • lower back or side pain
  • muscle weakness
  • painful or difficult urination
  • pale stools
  • pinpoint red spots on skin
  • redness, tenderness, itching, burning, or peeling of skin
  • red or irritated eyes
  • red, thick, or scaly skin
  • ringing or buzzing in the ears
  • spitting blood
  • yellow eyes or skin

Some side effects 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:

More common
  • Diarrhea
  • lessening or loss of sense of taste
  • loss of appetite
  • nausea or vomiting
  • stomach pain (mild)

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Uses of Penicillamine

  • It is used to treat Wilson's disease.
  • It is used to get rid of a protein called cystine from the body.
  • It is used to treat rheumatoid arthritis.
  • It may be given to you for other reasons. Talk with the doctor.

What are some things I need to know or do while I take Penicillamine?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Have your urine checked as you have been told by your doctor.
  • Take vitamin B6 (pyridoxine) as you were told by your doctor.
  • Follow the diet and workout plan that your doctor told you about.
  • You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
  • This medicine may lower the ability of your bone marrow to make blood cells that your body needs. This can lead to needing a blood transfusion and very bad and sometimes deadly bleeding problems or infections. Tell your doctor right away if you have signs of infection like fever, chills, or sore throat; any bruising or bleeding; or if you feel very tired or weak.
  • You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
  • Deaths from certain diseases like aplastic anemia, Goodpasture's syndrome, and myasthenia gravis have happened with penicillamine. Talk with your doctor.
  • Take good care of your teeth. See a dentist often.
  • If you are 65 or older, use this medicine with care. You could have more side effects.
  • Use birth control that you can trust to prevent pregnancy while taking penicillamine.
  • This medicine may cause harm to the unborn baby if you take it while you are pregnant.
  • If you are a woman and you miss a period, have unprotected sex, or think that your birth control has not worked, call your doctor right away.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

For all patients taking penicillamine:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
  • Signs of lupus like a rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs.
  • Feeling very tired or weak.
  • Any skin change.
  • Swollen gland.
  • Shortness of breath.
  • Muscle pain or weakness.
  • A burning, numbness, or tingling feeling that is not normal.
  • Mood changes.
  • Shakiness, trouble moving around, or stiffness.
  • Joint pain.
  • Change in eyesight.

Cystinuria patients:

  • Back pain, belly pain, or blood in the urine. May be signs of a kidney stone.

How do I store and/or throw out Penicillamine?

  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Pronunciation

(pen i SIL a meen)

Brand Names U.S.

  • Cuprimine
  • Depen Titratabs

Dosing Adult

Note: Dose reduction to 250 mg/day may be considered prior to surgical procedures. May resume normal recommended dosing post-operatively once wound healing is complete. Penicillamine administration increases requirement for pyridoxine. Patients may require a daily supplement of pyridoxine.

Cystinuria: Oral: 1 to 4 g/day in 4 divided doses; usual dose: 2 g/day; initiation of therapy at 250 mg/day with gradual upward titration may reduce the risk of unwanted effects. Note: Adjust dose to limit cystine excretion to 100 to 200 mg/day (<100 mg/day with history of stone formation).

Wilson's disease: Oral: Note: Dose that results in an initial 24-hour urinary copper excretion >2 mg/day should be continued for ~3 months; maintenance dose defined by amount resulting in <10 mcg serum free copper/dL.

Manufacturer's labeling: 750 to 1,500 mg/day in divided doses; maximum dose: 2,000 mg/day. Note: Limit daily dose to 750 mg/day in pregnant women; if planned caesarian, limit dose to 250 mg/day during the last 6 weeks of pregnancy and postoperatively until wound healing is complete.

Alternate recommendations (off-label dosing): To increase tolerability, therapy may be initiated at 250 to 500 mg/day then titrated upward in 250 mg increments every 4 to 7 days; usual maintenance dose: 750 to 1,000 mg/day in 2 divided doses; maximum: 1,000 to 1,500 mg/day in 2 to 4 divided doses (American Association for the Study of Liver Diseases [AASLD] guidelines) (Roberts 2008).

Administration

Oral: Doses ≤500 mg may be administered as a single dose; doses >500 mg should be administered in divided doses. For patients who have difficulty swallowing, the contents of the capsules may be administered in 15 to 30 mL of chilled puréed fruit or fruit juice within 5 minutes of preparation. Administer on an empty stomach (1 hour before or 2 hours after meals) and at least 1 hour apart from other drugs, milk, antacids, and zinc or iron-containing products.

Cystinuria: If administering 4 equal doses is not feasible, administer the larger dose at bedtime. Patients should drink about one pint of fluid at bedtime and another pint during the night.

Drug Interactions

Antacids: May decrease the serum concentration of PenicillAMINE. Consider therapy modification

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

Iron Salts: May decrease the absorption of PenicillAMINE. Only oral iron salts are a concern. Exceptions: Ferric Carboxymaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): May increase the serum concentration of PenicillAMINE. Management: Consider separating doses of the agents by 2 or more hours to minimize the effects of this interaction; however, the success of this action is unproven. Consider therapy modification

Polaprezinc: May decrease the serum concentration of PenicillAMINE. Consider therapy modification

Monitoring Parameters

Urinalysis, CBC with differential, platelet count, skin, lymph nodes, and body temperature twice weekly during the first month of therapy, then every 2 weeks for 5 months, then monthly; LFTs every 6 months; signs/symptoms of hypersensitivity

Cystinuria: Urinary cystine, annual X-ray for renal stones

Lead poisoning: Serum lead concentration (baseline and 7-21 days after completing chelation therapy); hemoglobin or hematocrit, iron status, free erythrocyte protoporphyrin or zinc protoporphyrin; neurodevelopmental changes

Wilson's disease: Serum non-ceruloplasmin bound copper, 24-hour urinary copper excretion, LFTs every 3 months (at least) during the first year of treatment; periodic ophthalmic exam

Urinalysis: Monitor for proteinuria and hematuria. A quantitative 24-hour urine protein at 1- to 2-week intervals initially (first 2-3 months) is recommended if proteinuria develops.

In Summary

Commonly reported side effects of penicillamine include: cheilosis, epigastric pain, glossitis, oral mucosa ulcer, ageusia, and dysgeusia. Other side effects include: thrombocytopenia. See below for a comprehensive list of adverse effects.

For Healthcare Professionals

Applies to penicillamine: oral capsule, oral tablet

Nervous system

Very common (10% or more): Blunting, diminution, or total loss of taste (12%)
Frequency not reported: Headache, dizziness, deterioration of neurological symptoms of Wilson's disease (dystonia, rigidity, tremor, dysarthria) following introduction of therapy in patients treated for this condition (this may be a consequence of mobilization and redistribution of copper from the liver to the brain), arthralgia, tinnitus, peripheral sensory and motor neuropathies (including polyradiculoneuropathy, i.e., Guillain-Barre Syndrome)[Ref]

Gastrointestinal

Very common (10% or more): Epigastric pain (17%), nausea (17%), vomiting (17%), diarrhea (17%)
Rare (0.01% to 0.1%): Mouth ulceration, stomatitis, glossitis
Frequency not reported: Pancreatitis, reactivated peptic ulcer[Ref]

Hematologic

Common (1% to 10%): Thrombocytopenia, leukopenia
Frequency not reported: Neutropenia (usually reversible), agranulocytosis (sometimes fatal), aplastic anemia (sometimes fatal), hemolytic anemia, lymphadenopathy, thrombotic thrombocytopenic purpura, red cell aplasia, monocytosis, leukocytosis, eosinophilia, thrombocytosis[Ref]

Renal

Common (1% to 10%): Proteinuria
Rare (less than 0.1%): Hematuria, renal vasculitis
Frequency not reported: Nephrotic syndrome, glomerulonephritis, Goodpasture's syndrome[Ref]

Musculoskeletal

Rare (less than 0.1%): Polymyositis, dermatomyositis
Frequency not reported: Lupus erythematosus, myasthenia gravis, rheumatoid arthritis, septic arthritis (in patients with rheumatoid arthritis), muscular weakness[Ref]

Dermatologic

Common (1% to 10%): Rash (early and/or later in therapy), pruritus
Rare (less than 0.1%): Alopecia, pseudoxanthoma elasticum, elastosis perforans, skin laxity, lichen planus
Frequency not reported: Urticaria, epidermolysis bullosa, exfoliative dermatitis, dermopathy, dermatomyositis, pemphigus, Stevens-Johnson syndrome[Ref]

Respiratory

Rare (less than 0.1%): Bronchial asthma
Frequency not reported: Pulmonary hemorrhage, dyspnea, pleural effusion, alveolitis, pulmonary fibrosis, bronchiolitis, pneumonitis[Ref]

Other

Frequency not reported: Deafness, fever, the chelating action of the drug may cause increased excretion of other heavy metals (in addition to copper) such as zinc, mercury, and lead[Ref]

Genitourinary

Rare (less than 0.1%): Breast enlargement[Ref]

Hepatic

Rare (less than 0.1%): Intrahepatic cholestasis, toxic hepatitis
Frequency not reported: Cholestatic jaundice, hepatic dysfunction, pancreatitis, increased serum alkaline phosphatase, increased lactic dehydrogenase, positive cephalin flocculation test, positive thymol turbidity test[Ref]

Ocular

Frequency not reported: Abnormal vision, optic neuritis[Ref]

Cardiovascular

Rare (less than 0.1%): Thrombophlebitis[Ref]

Endocrine

Very rare (less than 0.01%): Thyroiditis[Ref]

General

Both the frequency and severity of many side effects are dose related and vary according to the disease being treated. Initiating therapy at lower doses and titrating up helps to attenuate some side effects.[Ref]

Hypersensitivity

Rare (less than 0.1%): Allergic reactions including hypersensitivity[Ref]

Psychiatric

Frequency not reported: Confusion[Ref]

Some side effects of penicillamine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Why is this medication prescribed?

Penicillamine is used to treat Wilson's disease (an inherited condition that causes copper to build up in the body and may result in serious symptoms) and cystinuria (an inherited condition which can lead to kidney stones). It is also used in combination with other treatments to treat severe rheumatoid arthritis (a condition in which the body's immune system attacks its own joints, causing pain, swelling, and loss of function) that did not get better after treatment with other medications. Penicillamine is in a class of medications called heavy metal antagonists. It works to treat Wilson's disease by binding to the extra copper in the body and causing it to leave the body through the urine. It works to treat cystinuria by binding to the substance that makes kidney stones and preventing it from building up and forming stones. It works to treat rheumatoid arthritis by decreasing some actions of the immune system.

Other uses for this medicine

Penicillamine is also sometimes used as a follow up treatment for lead poisoning after it was treated with other medications. It is also sometimes used to treat certain types of liver disease. Talk to your doctor about the risks of using this medication for your condition.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

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