Depen (Penicillamine) - Oral

What Is Depen?

Depen (penicillamine) is an orally administered prescription medication used to treat cystinuria, Wilson's disease (WD), and in combination with other drugs to treat severe rheumatoid arthritis (RA).

Depen is a heavy metal antagonist further categorized as a chelating agent, a chemical that binds to certain metals.

For context, the term "heavy metal antagonist" refers to a group of medications that treat metal deficiencies in the blood, such as mercury and lead toxicity.

Depen contains the active ingredient penicillamine. Penicillamine works to treat WD by attaching to copper in the body and expelling it through urine.

Secondly, it treats cystinuria by attaching to the substance that makes kidney stones and preventing them from forming. Finally, it treats (alongside other medications) RA by suppressing disease activity in the immune system.

Depen is available as a brand-name medication available in the form of oral tablets. Moreover, penicillamine is available as a generic product as an oral capsule or tablet.

Comparatively, the brand-name drug, Cuprimine, contains the active ingredient penicillamine and is available in oral capsules.

Drug Facts

Generic Name: Penicillamine

Brand Name(s): Depen, Cuprimine

Drug Availability: Prescription

Therapeutic Classification: Antirheumatic

Available Generically: Yes

Controlled Substance: N/A

Administration Route: Oral

Active Ingredient: Penicillamine

Dosage Form(s): Tablet, capsule

What Is Depen Used For?

The Food and Drug Administration (FDA) has approved Depen to treat people with WD, cystinuria, or RA.

For context, WD is a rare medical condition that runs in families. People with this condition have a build-up of copper in the body. High amounts of copper may damage the brain, eyes, and liver. Potential WD brain-related symptoms may include speech problems and mood changes.

You may also see a greenish-brown ring surrounding the colored part of your eye. As for liver-related symptoms, you may notice yellowing of the skin or eyes.

In comparison, people with cystinuria have high amounts of cysteine in the kidneys and bladder. Therefore, those diagnosed with cystinuria may experience the development of stones in their bladder, kidney, or ureter.

Also, the symptoms of cystinuria may include nausea, blood in the urine (pee), and a lot of urinary tract infections (UTIs). You might also experience pain in the left or right lower back areas.

Finally, RA is a type of arthritis that causes pain and stiffness in your joints. RA can affect any joint in the body, but it most commonly affects a person's wrist and fingers. RA is more common in people who identify as female and is classified as an autoimmune disorder.

How to Take Depen

Take Depen by mouth up to four times daily—with the option of taking the largest dose at bedtime. Drink plenty of fluids (e.g., water) before bedtime and throughout the evening.

Make sure to take Depen one hour before or two hours after meals. You should also typically separate this medication by at least one hour from other medications, food, and milk.

You may also need to take Depen with a regular pyridoxine (vitamin B6) supplement.


When you receive Depen from the pharmacy, keep it at room temperature between 68 F to 77 F. This medication should also be protected from moisture.

In general, keep your medications tightly closed and out of the reach of children and pets, ideally locked in a cabinet or closet.

Avoid pouring unused and expired drugs down the drain or in the toilet. Instead, visit the FDA's website to learn where and how to discard all unused and expired medications.

You can also find disposal boxes in your area. Ask your healthcare provider if you have any questions about the best ways to dispose of your medications.

If you plan to travel with Depen, get familiar with your final destination's regulations. Checking with the U.S. embassy or consulate might be a helpful resource. In general, however, make a copy of your Depen prescription.

It's also a good idea to keep your medication in its original container from your pharmacy with your name on the label.

How Long Does Depen Take to Work?

Depending on your condition, you may notice some improvements in your symptoms within one to three months.

What Are the Side Effects of Depen?

This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your healthcare provider. You may report side effects to the FDA at or 800-FDA-1088.

Common Side Effects

Common side effects with Depen may include:

Severe Side Effects

Serious side effects with Depen may include:

Call 911 if your symptoms feel life-threatening.

Long-Term Side Effects

Possible long-term side effects with Depen may include:

  • Goodpasture's syndrome: Goodpasture's syndrome is a rare autoimmune condition where your immune system attacks your lungs and kidneys by mistake.
  • Lupus-like syndrome: If you have a lupus-like syndrome, you're likely experiencing symptoms similar to systemic lupus erythematosus (SLE). Some common symptoms may include butterfly rash on the face, severe tiredness, and joint pain or swelling.
  • Myasthenia-like syndrome: People with myasthenia-like syndrome may experience abnormal muscle weakness.
  • Nephrotic syndrome: If you have nephrotic syndrome, your kidneys aren't working as well. As a result, protein from your bloodstream may leak into the urine (pee).
  • Neurologic deterioration: Depen may cause irreversible impairment (dysfunction) of the brain.
  • Polyarthritis: People with polyarthritis experience joint pain.
  • Retinal hemorrhages: A retinal hemorrhage is bleeding in your retina, which is the light-sensitive part of your eye.
  • Thrombocytopenia: In thrombocytopenia, your blood platelets are low, which increases your chances of bleeding.

Report Side Effects

Depen may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your healthcare provider may send a report to the FDA's MedWatch Adverse Event Reporting Program or by phone (800-332-1088).

Dosage: How Much Depen Should I Take?

Drug Content Provided and Reviewed by IBM Micromedex®

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage forms (capsules or tablets):
    • For Wilson's disease (too much copper in the body):
      • Adults and teenagers—At first, 250 milligrams (mg) four times a day. After a while your doctor may need to increase the dose, depending on the amount of copper in your urine. Most people do not need more than 2000 mg a day (two 250-mg capsules or tablets four times a day).
      • Children (older than 6 months of age)—At first, 250 mg a day. After a while your doctor may need to increase the dose, depending on the amount of copper in your urine. Older children may need the same dose as adults.
    • For rheumatoid arthritis:
      • Adults—At first, 125 or 250 mg once a day. Your doctor may increase the dose after a few months, depending on how well the medicine is working and whether it causes any side effects. The largest dose is not more than 1500 mg a day (two 250-mg capsules or tablets three times a day).
      • Children—Use and dose must be determined by your doctor.
    • For preventing kidney stones:
      • Adults—At first, 500 mg (two 250-mg capsules or tablets) four times a day. After a while your doctor may need to change the dose, depending on the results of your urine tests. Some people may need as much as 4000 mg a day (four 250-mg capsules or tablets four times a day).
      • Children—The dose is based on body weight and must be determined by your doctor. At first, 7.5 mg per kilogram (kg) (about 3.5 mg per pound) of body weight four times a day. After a while your doctor may need to change the dose, depending on the results of your urine tests.


The following modifications (changes) should be kept in mind when using Depen:

Severe allergic reaction: Avoid using Depen if you have a known allergy to it or its ingredients. Ask your healthcare provider for a complete list of the ingredients if you're unsure.

Pregnancy: In rat animal studies, Depen was found to have negative effects on the fetus. There were also reports of some negative effects on the fetus in pregnant people. As a result, Depen use during pregnancy isn't typically recommended except for certain situations in WD or cystinuria.

Discuss with your healthcare provider if you plan to become pregnant or are pregnant. They will help you weigh the benefits and risks of Depen during your pregnancy.

Breastfeeding: Limited data suggests that penicillamine isn't present in human breastmilk, but this medication does appear to reduce copper and zinc levels in breastmilk. Presently, penicillamine has no reports of negative effects in nursing babies. Therefore, penicillamine appears to be safe while breastfeeding.

Talk with your healthcare provider if you plan to breastfeed. Your healthcare provider will help you weigh the benefits and harms of taking penicillamine while nursing. They can also discuss the different ways available to feed your baby.

Older adults over 65: There is limited information about Depen use in older adults to compare differences in responses between this age group and younger adults.

Children: There is limited effectiveness and safety information about Depen in children.

Kidney problems: Depen isn't recommended if you have kidney impairment and RA. Depen may result in worsening kidney damage.

Liver problems: There are rare reports of liver toxicity with Depen. As a result, your healthcare provider may want to closely monitor your liver function.

Missed Dose

If you accidentally forgot your Depen dose, take it as soon as you remember. If it's already close to your next scheduled dose, then skip the missed dose and take the following dose at your next scheduled dosing time. Don't try to double up to make up for the missed dose.

Try to find ways that work for you to help yourself remember to routinely keep your appointments and take your medication. If you miss too many doses, Depen might be less effective.

Overdose: What Happens If I Take Too Much Depen?

There is limited information available about Depen overdose.

If you think you're experiencing an overdose or life-threatening symptoms, seek immediate medical attention.

What Happens If I Overdose on Depen?

If you think you or someone else may have overdosed on Depen, call a healthcare provider or the Poison Control Center (800-222-1222).

If someone collapses or isn't breathing after taking Depen, call 911 immediately.


Drug Content Provided and Reviewed by IBM Micromedex®

Your doctor should check your progress at regular visits to make sure that this medicine 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 this medicine.

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 this medicine. 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.

What Are Reasons I Shouldn’t Take Depen?

Before receiving Depen, talk with your healthcare provider if any of the following applies to you:

  • Severe allergic reaction: If you have a severe allergic reaction to Depen or any of its components (ingredients), Depen isn't a viable option for you
  • Pregnancy: There are some reports of negative effects of Depen on the unborn fetus. As a result, Depen isn't typically recommended except for certain situations with WD or cystinuria.
  • Breastfeeding: Depen isn't present in breast milk, but this medication is linked to lower levels of copper and zinc in breast milk. There are no reports of negative effects, however, in nursing infants. As a result, Depen appears safe while breastfeeding.
  • Older adults over 65 years of age: There is limited information available to compare differences in responses to Depen between older and younger adults.
  • Children: There is little data available about Depen in children.
  • Kidney problems: If you have kidney impairment and RA, Depen isn't recommended. This medication may further worsen kidney problems.
  • Certain blood-related conditions: Depen isn't recommended if you develop certain blood-related conditions while taking Depen in the past. These blood-related conditions may include anemia and agranulocytosis. Agranulocytosis is a condition of low granulocytes, which are a type of white blood cell (WBC).

What Other Medications Interact With Depen?

Use caution when taking Depen with the following medications:

  • Gold compounds: Combining Depen with gold compounds might increase the likelihood of kidney problems. Auranofin (Ridaura) is an example of a gold compound for RA.
  • Iron-containing products: Iron-containing products might lower Depen's effectiveness. As a result, these products should be separated from Depen by at least two hours.
  • Zinc-containing products: Zinc-containing products may also reduce Depen's effectiveness. Therefore, these products should be separated from Depen by at least one hour.

These are a few key interactions with Depen. There might be other interactions. For more detailed information about medication interactions with Depen, talk with your healthcare provider.

And be sure to talk with your healthcare provider about any other medicines you take or plan to take, including over-the-counter (OTC), nonprescription products, vitamins, herbs, or plant-based medicines.

What Medications Are Similar?

Depen is a chelating agent. While it can be used for cystinuria, it's not a typical go-to option due to some concerning side effects. Therefore, the go-to treatment options for cystinuria are typically non-chelating medications.

As for WD, another chelating agent option is Syprine (trientine). Both Depen and Syprine are effective at treating WD, but Depen might have more side effects than Syprine. Since both of these medications are chelating agents, they're not typically used together.

Frequently Asked Questions

  • Where is Depen available?

    Depen is available as a prescription from your healthcare provider. Your local retail pharmacy may carry this medication. If your pharmacy doesn't have Depen in stock, the staff will likely be able to order it for you.

  • How much does Depen cost?

    Depen is available in the penicillamine generic version. So, this might save you some costs.

    If cost is a concern, some potentially helpful resources may include NeedyMeds, FundFinder, Simplefill, BenefitsCheckUp, Medicare Rights Center, State Pharmaceutical Assistance Programs (SPAPs), and Rx Outreach.

  • Why do I need to drink plenty of fluids with Depen?

    Drinking plenty of fluids may help lower your Depen dosage for cystinuria.

  • Why do I need to separate Depen from other medications, food, or drinks?

    Separating Depen from other medications, food, or drinks (e.g., milk) will help maximize Depen's absorption into your bloodstream. Separating Depen will also limit medication interactions.

  • Why do I need to take pyridoxine (vitamin B6)?

    Depen is linked to low vitamin B6. Therefore, you'll likely need a vitamin B6 supplement.

How Can I Stay Healthy While Taking Depen?

If you're taking Depen, chances are WD or cystinuria has been negatively affecting your quality of life. You may have tried different approaches or treatments.

While living with WD or cystinuria does have its challenges, there are ways to help improve your quality of life. Refer below for some general suggestions to help you manage WD or cystinuria.

  • Take WD or cystinuria-related medications as recommended by your healthcare provider.
  • Limit your intake of foods that are high in copper. Examples of food with high amounts of copper may include chocolate, mushrooms, nuts, and shellfish.
  • Drink plenty of fluids.
  • Move around to help pass cystine kidney stones.
  • Lay down on your left side with extended legs if you do lay down.
  • Use heat therapy to relieve kidney stone-related pain. Examples of heat therapy include using a heated pad, taking a warm shower, or soaking in a warm bath.
  • Consider using support groups or working with a mental health provider to help you find coping strategies to change the way you think, feel, react, or respond to living with WD or cystinuria.

Medical Disclaimer

Verywell Health's drug information is meant for educational purposes only and is not intended as a replacement for medical advice, diagnosis, or treatment from a healthcare provider. Consult your healthcare provider before taking any new medication(s). IBM Watson Micromedex provides some of the drug content, as indicated on the page.

20 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Ross Phan, PharmD, BCACP, BCGP, BCPS
Ross is a writer for Verywell with years of experience practicing pharmacy in various settings. She is also a board-certified clinical pharmacist and the founder of Off Script Consults.