Penicillamine (Depen): Basics, Side Effects & Reviews
Penicillamine (Depen)

Penicillamine (Depen)

Basics, Side Effects, Reviews & More

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Penicillamine (Depen) is used to treat Wilson's disease, cystinuria, and severe rheumatoid arthritis (RA). It has many side effects and requires careful monitoring by your provider. You'll have to follow specific instructions on how to time penicillamine (Depen) with your meals and other medications.


Cuprimine, Depen


Chelating agent


Not a controlled medication


Lower-cost generic available


Prescription only

Reviewed by:

Kristianne Hannemann, PharmD

Cydnee Ng, PharmD

Last reviewed on:

October 11, 2021


What is penicillamine (Depen)?

How penicillamine (Depen) works

Penicillamine (Depen) is a chelating agent, meaning that it attaches to heavy metals in your body. It helps your body get rid of certain substances that cause Wilson’s disease, cystinuria, and RA.

  • Wilson’s disease is a genetic condition that causes copper to build up in your liver, brain, and other organs. In Wilson's disease, penicillamine (Depen) attaches to the copper so your body can remove it through your urine. It also prevents more copper from building up in your body.

  • Cystinuria is a genetic condition that causes stones made of cystine (a protein) to form in your kidneys and bladder. Penicillamine (Depen) lowers the amount of cystine in your urine by attaching to it and forming a substance that your body can get rid of more easily. This lowers your risk of forming kidney stones and can help dissolve stones that are already formed.

  • RA is a condition where your body's immune system attacks your joints, which causes swelling and pain. The way penicillamine (Depen) works to help treat RA isn’t known.

What is penicillamine (Depen) used for?

  • Wilson's disease
  • Cystinuria
  • Severe rheumatoid arthritis (RA) when other medications haven’t worked well

Penicillamine (Depen) dosage forms

capsule icon
tablet icon

Typical dosing for penicillamine (Depen)

Take penicillamine (Depen) on an empty stomach, at least 1 hour before meals or 2 hours after meals, and at least 1 hour apart from any other foods or medications that contain aluminum, calcium, iron, magnesium, or zinc.

Wilson's disease

  • Adults: Typically, your dose will depend on how much copper is in your urine and blood. The dose is usually between 750 mg and 1,500 mg taken by mouth every day, split into two doses. If you aren’t tolerating higher doses, you can start with 250 mg per day and raise your dose slowly to avoid experiencing side effects.
  • Children: Ask your child’s provider about the appropriate dose your child should take.


  • Adults: The typical dose is 1 to 4 grams taken by mouth every day, split into four doses throughout the day. Your dose might be started at 250 mg every day and raised slowly to have better control of how well the medication works and to avoid side effects.
  • Children: The dose will depend on your child’s weight. The typical dose is 30 mg/kg of body weight taken by mouth every day, split into four doses throughout the day.

Rheumatoid arthritis

  • Adults: The typical starting dose is 125 mg or 250 mg taken by mouth every day. Depending on how you respond to the medication, your provider might slowly raise your dose to a typical maintenance range of 500 mg to 700 mg per day. Dosages more than 500 mg per day should be split into multiple doses throughout the day.
  • Children: It isn’t known if penicillamine (Depen) works well in children with juvenile RA. Ask your child’s provider about alternative medications.

This medication is available as a capsule called Cuprimine that's taken whole, as well as a tablet called Depen that can be split to make dose adjustments easier.

Frequently asked questions about penicillamine (Depen)

Pros and cons of penicillamine (Depen)


Thumbs UpCan be taken long term for maintenance

Thumbs UpOne of the few treatments for Wilson's disease

Thumbs UpWorks well to control the symptoms of Wilson’s disease

Thumbs UpCan be used in children with cystinuria


Thumbs DownNeed to take on an empty stomach

Thumbs DownMight need to take multiple times a day

Thumbs DownNot safe for use during pregnancy and in people with kidney problems

Thumbs DownCan take two or three months before seeing the full effects of the medication for RA

Thumbs DownCan be expensive, even as a generic medication

Pharmacist tips for penicillamine (Depen)

Capsule IconIf you are taking penicillamine (Depen) to treat cystinuria and can't take four equal doses during the day, it's important to take the largest dose at bedtime. Make sure to drink about a pint of water at bedtime and another pint once during the middle of the night. Your risk of kidney stones is higher at night when your urine is very concentrated and acidic, so it’s important to dilute your urine to prevent stones from forming.

Capsule IconIf you've stopped taking penicillamine (Depen), even just for a few days, it's important to restart it at a low dose and raise it slowly. This will help prevent side effects.

Capsule IconSince penicillamine (Depen) can cause serious side effects, including blood, kidney, and liver problems, you might need to take regular blood and urine tests. This is how your provider can monitor these side effects.

Capsule IconSome people who take penicillamine (Depen) experience a change or loss in taste. This can last 2 to 3 months or longer after you start the medication, but it should go away on its own without any treatment.

Capsule IconYou might notice skin changes, like red spots in certain areas of your skin or skin that gets damaged more easily, while taking penicillamine (Depen). This is because the medication raises the amount of soluble collagen (a protein) in your body, which lowers the strength of your skin and prevents normal healing.

Capsule IconIf you need to have surgery, make sure to tell your provider that you are taking this medication, since your dose might need to be lowered. Once you have fully healed, your dose can be raised again.

Capsule IconBecause penicillamine (Depen) raises your body's requirement for vitamin B6, ask your provider about taking supplements while taking this medication.

Capsule IconYou might need to be on a special diet in addition to taking penicillamine (Depen) to treat Wilson’s disease or cystinuria. If you have Wilson’s disease, you’ll need to be on a diet containing no more than 1 mg or 2 mg of copper per day. If you have cystinuria, you’ll need to be on a low methionine (protein) diet. Ask your provider about what foods you should avoid.

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What are the side effects of penicillamine (Depen)?

With any medication, there are risks and benefits. Even if the medication is working, you may experience some unwanted side effects.

Warning Small Contact your doctor immediately if you experience any of the following:

  • Goodpasture syndrome (a rare condition where your body's immune system attacks your kidneys and lungs): feeling tired, trouble breathing, chest pain, coughing up blood
  • Low white blood cells: getting fevers, sore throat, or chills too often or if they don’t go away
  • Low platelets: bruising, bleeding
  • Kidney damage: blood in your urine

Caution Small The following side effects may get better over time as your body gets used to the medication. Let your doctor know immediately if you continue to experience these symptoms or if they worsen over time.

Common side effects

  • Stomach problems, such as loss of appetite, stomach pain, nausea, vomiting, and diarrhea (17%)
  • Loss of taste (12%)
  • Protein in urine (6%)
  • Rash (5%)
  • Low platelets (4%)
  • Low white blood cells (2%)

Other side effects

  • Fever
  • Swollen lymph nodes
  • Joint pain
  • Lupus-like symptoms (muscle pain, feeling tired, rash)
  • Hives
  • Shedding of your skin (exfoliative dermatitis)
  • Stomach ulcer
  • Liver failure
  • Inflammation of your pancreas (pancreatitis)
  • Mouth sores
  • Blood in urine
  • Ringing in your ears
  • Vision changes
  • Movement problems
  • Anxiety
  • Feeling annoyed
  • Mood problems

Source: DailyMed

The following side effects have also been reported:

Side effects that you should report to your doctor or health care professional as soon as possible:

  • allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
  • black, tarry stools
  • breathing problems
  • changes in vision
  • dark urine
  • dizzy, lightheaded
  • fever, chills, sore throat
  • joint pain
  • mouth sores
  • numbness, tingling pain
  • redness, blistering, peeling or loosening of the skin, including inside the mouth
  • swollen or painful glands
  • trouble passing urine or change in the amount of urine
  • unusual bleeding or bruising
  • unusually weak or tired

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

What are the risks and warnings for penicillamine (Depen)?

Penicillamine (Depen) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options

Monitoring by your provider

Warning Icon You should be under close supervision of your provider while taking penicillamine (Depen). Tell your provider if you have any side effects while taking this medication.

Serious blood problems

  • Risk factors: History of blood problems | Taking medications like gold therapy, antimalarial medications, cytotoxic medications, oxyphenbutazone, or phenylbutazone

Penicillamine (Depen) can cause blood problems, like low white blood cells, low red blood cells, or low platelets (blood cells that help clot blood when you get a cut). Taking certain medications like gold therapy (e.g., Ridaura (auranofin)), antimalarial medications (e.g., mefloquine), cytotoxic medications (e.g., methotrexate), oxyphenbutazone, or phenylbutazone can raise your risk of developing blood problems, because they can also cause these problems. Let your provider know if you have a history of blood problems or are taking any medications that might cause them before starting penicillamine (Depen). While you're taking this medication, you'll probably need to take blood tests so your provider can monitor your blood. If you notice a fever, sore throat, chills, bruising, or bleeding, contact your provider immediately.

Serious kidney problems

  • Risk factors: History of kidney problems | Taking medications like gold therapy, antimalarial medications, cytotoxic medications, oxyphenbutazone, or phenylbutazone

Penicillamine (Depen) might cause you to have protein or blood in your urine, which is a sign of kidney damage. This is more likely to happen if you have a history of kidney problems or take certain medications. Don’t take penicillamine (Depen) if you currently have kidney problems, and talk to your provider about alternative medications. You'll have to take regular urine tests while you're taking penicillamine (Depen) so your provider can check your kidneys. If you notice any blood in your urine, tell your provider right away.


Some people might experience a fever in response to taking penicillamine (Depen), usually in the second or third week of therapy. If you experience a fever, stop taking the medication and let your provider know right away. If you're taking it to treat Wilson's disease or cystinuria, your provider might start it again at a low dose once your fever goes away and then raise your dose slowly. For RA, your provider will likely change your medication, because there are other options.

Allergic reactions

You might notice a rash as early as during the first few months of taking penicillamine (Depen), or as late as six months or more after starting it. Let your provider know if you get a rash. If you get a very itchy rash on your stomach or back after six months or longer of starting penicillamine (Depen), your provider might stop the medication. If you experience a fever, swollen lymph nodes, or joint pain with a rash, tell your provider right away.

Vitamin and mineral deficiency

  • Risk factors: Children | Menstruating women | Low copper or methionine diet

Penicillamine (Depen) can cause lower vitamin B6 levels in your body, an important nutrient that helps keep you healthy. The medication attaches to vitamin B6 and prevents it from working in your body. In addition, if you need to be on a special diet for your condition, you might not be getting enough protein from your diet. This can cause low iron levels in your body. Ask your provider if you or your child should take supplements while taking penicillamine (Depen) to make sure your body gets the nutrients it needs.

Nerve problems

Some people using penicillamine (Depen) have experienced nerve problems affecting different parts of the body. Symptoms include drooping eyelids, double vision, and muscle weakness. Tell your provider immediately if you notice any of these side effects.

Skin problems

Some people taking penicillamine (Depen) have developed pemphigus, a condition where your body's immune system attacks your skin and causes blisters and sores. If this happens, you might need to stop penicillamine (Depen) and get treated with medications called steroids or immunosuppressants. Tell your provider if you notice any blisters or sores on your skin.

How much does penicillamine (Depen) cost?

Penicillamine (Depen) is available as a generic medication and may be significantly cheaper compared to the brand version. Unless there is a specific reason you need the brand, the generic medication will be a better value. For even more savings, use a GoodRx coupon and pay just a fraction of the retail price.

Lowest GoodRx Price
Cuprimine, Depen (brand)


Lowest GoodRx Price
penicillamine (generic)


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Pricing based on most commonly-filled versions: 120 tablets of penicillamine 250mg

What are alternatives to penicillamine (Depen)?

There are a number of medications that your doctor can prescribe in place of penicillamine (Depen). Compare a few possible alternatives below.

Penicillamine (Depen)
Drug Class:Chelating agent


lowest GoodRx price

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Tiopronin (Thiola)
Drug Class:Urinary tract product


lowest GoodRx price

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