penicillamine (Rx)

Brand and Other Names:Cuprimine, Depen
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 250mg

capsule

  • 125mg
  • 250mg

Wilson's Disease

250 mg PO QID; dosage range 500-1500 mg/day

Pregnancy: Not to exceed 500-750 mg/day

Planned cesarean section: Reduce dose to 250 mg/day for the last 6 weeks of pregnancy and postoperatively until wound healing completed

Dosing considerations

  • Adjust dose to achieve urinary copper excretion of 0.5-1 mg/day
  • Free copper levels in serum: Maintain at <10 mcg/dL

Arsenic Poisoning

100 mg/kg/day PO divided q6hr x5 days  

If used for chronic arsenic poisoning, endpoint: 24 hours urinary arsenic <50 mcg/L

Rheumatoid Arthritis

Initial: 125-250 mg/day PO

Maintenance: May be increased by 125-250 mg/day q1-3Months up to 500-750 mg/day, may be increased further if no response and patient tolerates

Lead Poisoning

1-1.5 g qDay PO or divided BID-TID x1-6 months

Administration

Usually given with 10-25 mg/day pyridoxine

Take on empty stomach; last dose given at least 3 hr after evening meal

Other Indications & Uses

Cystinuria

Off-label: Lead toxicity (used following Ca-EDTA or dimercaprol; succimer preferred); copper, mercury, arsenic poisoning (chronic-only if BAL/DMSA unavailable); primary biliary cirrhosis

Dosage Forms & Strengths

tablet

  • 250mg

capsule

  • 125mg
  • 250mg

Lead Poisoning

Considered 3rd-line therapy

20-40 mg/kg/day PO divided q8hr  

Wilson's Disease

20 mg/kg/day PO divided q12hr  

Cystinuria

30 mg/kg/day PO divided BID/QID; not to exceed 1 g/day  

Juvenile Rheumatoid Arthritis

1st step (2 months): 5 mg/kg PO qDay x2 months  

2nd step (4 months): 10 mg/kg PO qDay x4 months

Administration

Usually given with 10-25 mg/day pyridoxine

Take on empty stomach; last dose given at least 3 hours after evening meal

Cystinuria: drink plenty of fluids

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Interactions

Interaction Checker

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    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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             activity indicator 

            Contraindicated (0)

              Serious - Use Alternative (2)

              • gold sodium thiomalate

                gold sodium thiomalate, penicillamine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased potential for serious bone marrow suppression or renal toxicity.

              • sodium sulfate/potassium sulfate/magnesium sulfate

                sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of penicillamine by Other (see comment). Avoid or Use Alternate Drug. Comment: Administer penicillamine at least 2 hr before and no less than 6 hr after each dose to avoid chelation with magnesium. .

              Monitor Closely (27)

              • aluminum hydroxide

                aluminum hydroxide decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • calcium carbonate

                calcium carbonate decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • carbonyl iron

                carbonyl iron decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Interaction only with oral iron administration.

              • copper

                copper decreases effects of penicillamine by pharmacodynamic antagonism. Use Caution/Monitor.

              • ferric maltol

                ferric maltol decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Interaction only with oral iron administration.

              • ferrous fumarate

                ferrous fumarate decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Interaction only with oral iron administration.

              • ferrous gluconate

                ferrous gluconate decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Interaction only with oral iron administration.

              • ferrous sulfate

                ferrous sulfate decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Interaction only with oral iron administration.

              • iron dextran complex

                iron dextran complex decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Interaction only with oral iron administration.

              • iron sucrose

                iron sucrose decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Interaction only with oral iron administration.

              • magnesium chloride

                magnesium chloride decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • magnesium citrate

                magnesium citrate decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • magnesium hydroxide

                magnesium hydroxide decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • magnesium oxide

                magnesium oxide decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • magnesium sulfate

                magnesium sulfate decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • magnesium supplement

                magnesium supplement will decrease the level or effect of penicillamine by Other (see comment). Modify Therapy/Monitor Closely. Drug may form a chelate with polyvalent cations; may decrease absorption by the intestinal tract; applies to oral forms; may administer 1 hr from polyvalent cation administration

              • peramivir

                penicillamine increases levels of peramivir by decreasing renal clearance. Use Caution/Monitor. Caution when peramivir coadministered with nephrotoxic drugs.

              • polysaccharide iron

                polysaccharide iron decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Interaction only with oral iron administration.

              • promazine

                promazine increases toxicity of penicillamine by unspecified interaction mechanism. Use Caution/Monitor. Enhanced myelosuppression.

              • rose hips

                rose hips decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Interaction only with oral iron administration.

              • selenium

                selenium will decrease the level or effect of penicillamine by cation binding in GI tract. Modify Therapy/Monitor Closely. Separate penicillamine administration from ingestion of polyvalent cations by at least 1 h.

              • sodium bicarbonate

                sodium bicarbonate decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • sodium citrate/citric acid

                sodium citrate/citric acid decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

              • sodium picosulfate/magnesium oxide/anhydrous citric acid

                sodium picosulfate/magnesium oxide/anhydrous citric acid decreases levels of penicillamine by cation binding in GI tract. Use Caution/Monitor. Take at least 2 hours before and not less than 6 hours after administration of sodium picosulfate, magnesium oxide and anhydrous citric acid to avoid magnesium chelation .

              • sodium sulfate/?magnesium sulfate/potassium chloride

                sodium sulfate/?magnesium sulfate/potassium chloride decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer penicillamine at least 2 hr before and no less than 6 hr after each dose to avoid chelation with magnesium. .

              • sodium sulfate/potassium sulfate/magnesium sulfate

                sodium sulfate/potassium sulfate/magnesium sulfate decreases levels of penicillamine by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer penicillamine at least 2 hr before and no less than 6 hr after each dose to avoid chelation with magnesium. .

              • tenofovir DF

                penicillamine, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

                penicillamine increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

              Minor (3)

              • digoxin

                penicillamine decreases levels of digoxin by unknown mechanism. Minor/Significance Unknown.

              • pyridoxine

                penicillamine decreases levels of pyridoxine by unspecified interaction mechanism. Minor/Significance Unknown.

              • pyridoxine (Antidote)

                penicillamine decreases levels of pyridoxine (Antidote) by unspecified interaction mechanism. Minor/Significance Unknown.

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              Adverse Effects

              >10%

              Worsening neurologic symptoms (10-50% pts with Wilson's disease)

              Adverse effects requiring discontinuation of treatment

              • Discontinued in 20-30% of pts with Wilson's disease
              • Diarrhea (17%)
              • Taste alteration (12%)

              1-10%

              Proteinuria (6%)

              Rash (early and late 5%)

              Thrombocytopenia (4-5%)

              Leukopenia (2-5%)

              Frequency Not Defined

              Nausea/vomiting

              Fever

              Anorexia

              Pemphigus

              Oral lichenoid reaction

              Myasthemia gravis

              Neuropathy

              Optic neuritisTinnitus

              Goodpasture's syndrome

              Renal failure

              positive ANA

              Hepatitis

              Pancreatitis

              Hemolytic anemia

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              Warnings

              Contraindications

              Penicillin allergy, discontinue if immune reactions

              History of penicillamine-related aplastic anemia, agranulocytosis

              Renal insufficiency (avoid if CrCl <50 mL/min)

              Concurrency with gold salts, antimalarials, immunosuppressants, phenylbutazone

              Cautions

              Antacids, digoxin and iron (PO) decr levels and/or activity

              Reactive airway disease

              Associated with obliterative bronchiolitis

              Increases the body's requirement for pyridoxine

              Potential for development of (reversible) myasthenia gravis and other neurologic symptoms

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              Pregnancy & Lactation

              Pregnancy Category: D; allowed only in Wilson's: not to exceed 750 mg/d; contraindicated for rheumatoid arthritis and cystinuria

              Lactation: little information available, mfr states do not nurse

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Absorption: 40-70%

              Peak Plasma Time: 1-3 hr

              Peak Plasma Concentration: (250 mg dose) 1-2 mg/L

              Metabolism: small amount in liver

              Protein Bound: >80%

              Excretion: urine

              Mechanism of Action

              Chelates gold, copper, mercury, and arsenic

              Cystinuria: forms disulfide bonds with cysteine and facilitates excretion of cysteine-penicillamine complex rather than cystine

              Rheumatoid arthris: unknown; depresses T-cell activity in vitro

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              Images

              BRAND FORM. UNIT PRICE PILL IMAGE
              penicillamine oral
              -
              250 mg capsule
              penicillamine oral
              -
              250 mg capsule
              penicillamine oral
              -
              250 mg capsule
              penicillamine oral
              -
              250 mg capsule

              Copyright © 2010 First DataBank, Inc.

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              Patient Handout

              Patient Education
              penicillamine oral

              PENICILLAMINE - ORAL

              (PEN-i-SIL-a-meen)

              COMMON BRAND NAME(S): Cuprimine, Depen

              USES: This medication is used to treat rheumatoid arthritis, Wilson's disease (a condition in which high levels of copper in the body cause damage to the liver, brain, and other organs), and a certain disorder which causes kidney stones (cystinuria). For the treatment of rheumatoid arthritis, penicillamine is known as a disease-modifying antirheumatic drug (DMARD). It helps to decrease pain/tenderness/swelling in the joints. For the treatment of Wilson's disease, penicillamine binds to copper and helps it to be removed from the body. Decreasing copper levels helps to improve liver function and the mental/mood/nerve problems (such as confusion, difficulty speaking/walking) caused by the disease. For the treatment of cystinuria, penicillamine helps to decrease the amount of a certain substance (cystine) in the urine which can cause kidney stones.

              HOW TO USE: Take this medication by mouth on an empty stomach (1 hour before or 2 hours after meals) as directed by your doctor. Take this medication at least 1 hour apart from other drugs (especially antacids), milk, or food.Dosage is based on your medical condition and response to treatment.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.Your doctor may also direct you to take vitamin B6 (pyridoxine) and iron. Follow your doctor's instructions carefully. If you need to take iron or other products that contain minerals (such as zinc), take it at least 2 hours before or after taking penicillamine. Consult your doctor before taking any products containing minerals since they may block the absorption of penicillamine.For the treatment of rheumatoid arthritis, it may take 2 to 3 months before you see any improvement in your condition.For the treatment of Wilson's disease, follow the diet recommended by your doctor to get the most benefit from this medication. Your condition may not improve for 1 to 3 months and may actually get worse when you start this medication. Tell your doctor right away if your condition continues to worsen after a month of treatment.For the treatment of cystinuria, follow the diet recommended by your doctor to get the most benefit from this medication. Drink plenty of water unless your doctor directs you otherwise.Tell your doctor if your condition does not improve or if it worsens.

              SIDE EFFECTS: Stomach/abdominal pain, nausea/vomiting, loss of appetite, diarrhea, and decreased sense of taste may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if any of these unlikely but serious side effects occur: signs of infection (such as fever, persistent sore throat, swollen lymph nodes), easy bruising/bleeding, unusual tiredness, rapid breathing, skin blisters, mouth sores, new or worsening joint pain, thinning/wrinkling skin.Tell your doctor right away if any of these rare but serious side effects occur: signs of kidney problems (such as change in the amount of urine, bloody urine), coughing up blood, shortness of breath, muscle weakness, eye problems (such as drooping eyelids, blurred vision), persistent nausea/vomiting, severe stomach/abdominal pain, dark urine, yellowing eyes/skin.A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

              PRECAUTIONS: Before taking penicillamine, tell your doctor or pharmacist if you are allergic to it; or to penicillins; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: a previous severe reaction to penicillamine (such as aplastic anemia, agranulocytosis), kidney disease, blood/bone marrow disorders (such as thrombocytopenia).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Penicillamine is not recommended for use during pregnancy. It may harm an unborn baby. However, it may sometimes be used during pregnancy in certain situations (such as treating Wilson's disease). Consult your doctor for more details.It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

              DRUG INTERACTIONS: See also How to Use section.The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.To help your doctor and pharmacist give you the best care, be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.Some products that may interact with this drug include: digoxin, gold salts (such as auranofin), drugs to treat malaria (such as chloroquine), phenylbutazone, other drugs that decrease bone marrow function (such as azathioprine, cancer chemotherapy, trimethoprim/sulfamethoxazole).This document does not contain all possible drug interactions. Keep a list of all the products you use. Share this list with your doctor and pharmacist to lessen your risk for serious medication problems.

              OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

              NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as complete blood count, hematocrit/hemoglobin, liver function, urine test, physical exam) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

              MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

              STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

              Information last revised January 2019. Copyright(c) 2021 First Databank, Inc.

              IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.