Penicillamine (Depen) is used to treat Wilson's disease, cystinuria, and severe rheumatoid arthritis (RA). It has many side effects, such as upset stomach and changes in taste, and requires careful monitoring by your provider. The dose is taken on an empty stomach, but you'll have to follow specific instructions on how to time penicillamine (Depen) with your meals and other medications. This medication comes as tablets (under the brand name Depen) and capsules (under the brand name Cuprimine). Penicillamine (Depen) is also available as a lower-cost generic.
Wilson's disease
Cystinuria
Severe rheumatoid arthritis (RA) when other medications haven’t worked well
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 and cystinuria.
Wilson’s disease is a genetic condition that causes copper to build up in your liver, brain, and other organs. Penicillamine (Depen) attaches to the copper so your body can remove it through your urine.
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.
Rheumatoid arthritis (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.
Source:Â DailyMed
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
joint pain
lesions on the face, neck, scalp, and/or trunk
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
Rare
Abdominal or stomach pain (severe)
blisters on skin
bloody or black, tarry stools
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:
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.
Can take long term for maintenance therapy
One of the few recommended treatments for Wilson's disease
Can help control symptoms of Wilson’s disease
Can use in children with cystinuria
Need to take on an empty stomach
Might need to take multiple times a day
Can take 2 or 3 months before seeing the full effects of the medication for RA
Not safe for use during pregnancy and in people with kidney problems
Take penicillamine (Depen) at least 1 hour before meals or 2 hours after meals. Also make sure to take penicillamine (Depen) at least 1 hour apart from any other foods or medications that contain aluminum, calcium, iron, magnesium, or zinc. Food and products containing these minerals can affect how well penicillamine (Depen) gets absorbed into the body.
Tips for taking penicillamine (Depen) to treat cystinuria: If you can't take four equal doses during the day, it's important to take the largest dose at bedtime. Make sure to drink about 2 cups of water at bedtime and another 2 cups 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.
Since penicillamine (Depen) can cause serious side effects, including blood, kidney, and liver problems, you might need to get regular blood and urine tests done during treatment. This is how your provider can check for these side effects.
Some 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.
You might notice skin changes, like red spots in certain areas of your skin or skin that gets damaged more easily, while you're taking penicillamine (Depen). The medication can affect the strength of your skin and prevent normal healing.
Make sure to let your provider know if you have a planned surgery. Because penicillamine (Depen) can affect wound healing, your dose might need to be lowered so you can make a full recovery from surgery. Once you've healed completely, your dose can be raised again.
Because penicillamine (Depen) raises your body's requirement for vitamin B6, ask your provider about taking supplements during treatment.
In addition to taking penicillamine (Depen), you might need to be on a special diet 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 or nutritionist about a diet plan that's best for you.
If you've stopped taking penicillamine (Depen), even just for a few days, let your provider know before restarting the medication. It's important that you restart the medication at a low dose to help prevent side effects.
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.
You should be under close supervision of your provider while you're taking penicillamine (Depen). This medication can cause many side effects, like blood problems, kidney problems, skin problems, and fever. You'll need regular lab work done and follow ups with your provider to make sure penicillamine (Depen) is safe for you. Tell your provider if you have any side effects while taking this medication.
Risk factors: History of blood problems | Taking medications like gold therapy, antimalarial medications, cytotoxic medications, oxyphenbutazone, or phenylbutazone
Penicillamine (Depen) can cause potential blood problems. These problems include low white blood cells, low red blood cells, and 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, cytotoxic medications (e.g., methotrexate), oxyphenbutazone, or phenylbutazone can raise your risk of developing blood 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 need to get blood tests done so your provider can check your blood cell counts. If you notice a fever, sore throat, chills, bruising, or bleeding, contact your provider right away.
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 can be 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 get regular urine tests done while you're taking penicillamine (Depen) so your provider can check your kidney health. 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 penicillamine (Depen) 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 probably change your medication because there are other options available.
Penicillamine (Depen) can sometimes cause rash. Rashes can occur as early as during the first few months of treatment or as late as 6 months or more after starting penicillamine (Depen). Let your provider know if you get a rash. If you get a very itchy rash on your stomach or back after 6 months or longer of penicillamine (Depen) treatment, your provider might stop the medication. And if you experience a rash with fever, swollen lymph nodes, or joint pain, tell your provider right away.
Risk factors: Children | Menstruating women | Low copper or methionine diet
Penicillamine (Depen) can cause lower vitamin B6 levels in your body. Vitamin B6 is an important nutrient that helps keep you healthy. Penicillamine (Depen) attaches to vitamin B6 and prevents the vitamin 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.
Some people using penicillamine (Depen) have experienced nerve problems affecting different parts of the body. Sometimes, these nerve problems are worse when you first start the medication. But, they should get better as you continue treatment. Symptoms of nerve problems can include drooping eyelids, double vision, and muscle weakness. Tell your provider right away if you notice any of these side effects.
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.
This medication is available as tablets and capsules. Take penicillamine (Depen) on an empty stomach and separate from other foods or medications that contain certain minerals. See Pharmacist Tips for more details on how to take penicillamine (Depen).
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 might start with 250 mg per day, and then your provider can raise your dose slowly to avoid side effects.
Children: Ask your child’s provider about the appropriate dose your child should take.
Cystinuria
Adults: The typical dose is 1 to 4 grams taken by mouth every day, split into four doses throughout the day. You might start at a dose of 250 mg every day. Then, your provider can raise the dose slowly. This helps better control how well the medication works and avoid side effects.
Children: The dose will depend on your child’s body weight. The typical dose is 30 mg/kg of 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 dose range of 500 mg to 700 mg per day. Dosages of 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.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Currently pregnant (except for people with Wilson’s disease or certain people with cystinuria)
Currently breastfeeding
History of blood problems after taking penicillamine (Depen)
Have rheumatoid arthritis and kidney problems
Wilson's disease
Cystinuria
Severe rheumatoid arthritis (RA) when other medications haven’t worked well
Prevention of cystine kidney stones
Wilson's disease in people who can't take penicillamine (Depen)
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Arthritis Foundation. (n.d.). Juvenile idiopathic arthritis (JIA).
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National Institute of Diabetes and Digestive and Kidney Diseases. (2018). Definition & facts for Wilson disease.
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Navinta LLC. (2022). PENICILLAMINE capsule [package insert]. DailyMed.
Schilsky, M. L., et al. (2022). A multidisciplinary approach to the diagnosis and management of Wilson disease: Executive summary of the 2022 practice guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology.
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