Penicillamine (Cuprimine, Depen) - Uses, Side Effects, and More

What are the most common side effects of penicillamine?

The most common side effects of penicillamine are listed below. Tell your health care provider if you have any of these side effects that bother you.

• Diarrhea
• Taste changes (see below)
• Protein in urine (proteinuria) (see below)
• Rash
• Blood disorders (see below)

There may be other side effects of penicillamine that are not listed here. Contact your health care provider if you think you are having a side effect of a medicine. In the U.S., you can report side effects to the FDA at www.fda.gov/medwatch or by calling 800-FDA-1088 (800-332-1088). In Canada, you can report side effects to Health Canada at www.health.gc.ca/medeffect or by calling 866-234-2345.

What are the serious side effects of penicillamine?

While less common, the most serious side effects of penicillamine are described below, along with what to do if they happen.

Severe Allergic Reactions. Penicillamine may cause allergic reactions, which can be serious. Stop taking penicillamine and get help right away if you have any of the following symptoms of a serious allergic reaction.

• Breathing problems or wheezing
• Racing heart
• Fever or general ill feeling
• Swollen lymph nodes
• Swelling of the face, lips, mouth, tongue, or throat
• Trouble swallowing or throat tightness
• Itching, skin rash, or pale red bumps on the skin called hives
• Nausea or vomiting
• Dizziness, feeling lightheaded, or fainting
• Stomach cramps
• Joint pain

Blood Disorders. Penicillamine can cause blood disorders, such as agranulocytosis, aplastic anemia, hemolytic anemia, low platelet levels (thrombocytopenia), and low white blood cell levels (leukopenia). Stop taking penicillamine and get help right away if you have any of the following symptoms of blood disorders.

• Fever
• Shortness of breath
• Pale or yellowish skin
• Easy bruising or bleeding
• Frequent infections
• Unusual weakness or tiredness
• Dizziness, lightheadedness, or feeling like you are about to pass out
• Headache
• Fast or abnormal heartbeat

Protein or Blood in Urine. Penicillamine can cause excess protein and blood to pass in your urine (pee). These may be early signs of kidney damage. Call your health care provider right away if you have any of the following symptoms of kidney damage.

• Foamy or bubbly pee
• Blood in your pee
• Swelling in your feet, ankles, or legs
• Weakness or unusual tiredness
• Trouble catching your breath or chest pain or pressure
• Muscle cramps
• Upset stomach or vomiting

Liver Damage. Liver damage, also called hepatotoxicity, can happen when taking penicillamine. Call your health care provider right away if you have any of the following symptoms of liver damage.

• Nausea or vomiting
• Stomach or belly pain
• Fever
• Weakness or unusual tiredness
• Itching
• Loss of appetite
• Light-colored poop
• Dark-colored urine (pee)
• Your skin or the whites of your eyes turning yellowish (also called jaundice)

Goodpasture Syndrome. Penicillamine may be associated with Goodpasture syndrome, a rare condition that affects your lungs and kidneys. Tell your health care provider right away if you have any of the following symptoms of Goodpasture syndrome.

• Unusual tiredness
• Nausea and vomiting
• Trouble breathing
• Pale skin
• Trouble peeing, pain when you pee, or blood in your pee
• Swelling in the hands, legs, and feet
• High blood pressure
• Back pain

Obliterative Bronchiolitis. Penicillamine may be associated with obliterative bronchiolitis, a rare lung condition that causes breathing difficulties due to scarring and narrowing of airways. Tell your health care provider if you have any of the following symptoms of obliterative bronchiolitis.

• Shortness of breath, especially with exertion
• Unexplained cough
• Wheezing

Pemphigus. Penicillamine may cause pemphigus, which refers to a group of conditions that causes blisters on your skin as well as the inside of your mouth, nose, throat, eyes, and genitals. Stop taking penicillamine and tell your health care provider if you notice any blisters on these areas.

Myasthenia Gravis. Penicillamine may be associated with myasthenia gravis, a condition that weakens certain muscles in your body by affecting the nerve signals that move the muscles. Eye muscle problems are often early signs of myasthenia gravis. Tell your health care provider if you have any of the following symptoms associated with myasthenia gravis.

• Double vision (diplopia)
• Drooping of upper eyelids (ptosis)
• Slurred speech
• Weak or hoarse-sounding voice
• Trouble chewing or swallowing
• Changes in facial expressions
• Shortness of breath
• Other muscle problems, such as trouble using your arms or legs

Drug Fever. Penicillamine may cause a marked increase in body temperature (drug fever). This usually happens two to three weeks after you start taking penicillamine. You can sometimes have a rash with drug fever. Tell your health care provider if you have fever after starting penicillamine.

Lupus-Like Symptoms. Penicillamine can cause symptoms that look like a condition called lupus. Call your health care provider right away if you have any of the following symptoms. 

• Rash
• Joint pain
• Fever
• Weakness or unusual tiredness
• Swollen glands
• Reduced need to pee
• Pink, red, or brown pee 
• Swelling

Mouth Ulcers. Penicillamine may cause ulcers and inflammation in your mouth. The risk may be higher if you are taking higher doses of penicillamine. Tell your health care provider if you notice any ulcers, pain, or swelling in and around your mouth.

Taste Changes. Penicillamine may be linked with a loss of taste or a blunted taste (hypogeusia). This may last two to three months or longer. It usually goes away on its own. Tell your health care provider if you notice any changes in how things taste.

Iron Deficiency. Penicillamine may be linked with iron deficiency. The risk is higher in children and if you have a menstrual period. A low copper diet (for Wilson’s disease) or a low methionine diet (for cystinuria), which may be recommended, can sometimes increase the risk of iron deficiency. Tell your health care provider if you notice any symptoms of iron deficiency, such as fatigue, dizziness, lightheadedness, or headaches.

Collagen Changes. Penicillamine may cause changes in the collagen structure of your skin. This may lead to weakening of the skin or excessive wrinkling. These may be more common in areas that are frequently subject to pressure, such as your elbows, knees, and buttocks. Broken blood vessels may also cause small red or purple spots to form under your skin. Tell your health care provider if you start having frequent skin breaks or increased wrinkling.