Select therapeutic use:

Arthritis/rheumatic disorders:

Indications for: DEPEN

Severe, active rheumatoid arthritis in patients who have failed to respond to an adequate trial of conventional therapy.

Adult Dosage:

Take on an empty stomach at least 1hr before meals or 2hrs after meals, and at least 1hr apart from any other drug, food, or milk. Supplement with daily pyridoxine if nutrition is impaired. Do not give mineral supplements. Dosages >500mg/day should be administered in divided doses. Initially 125mg or 250mg as a single daily dose; increase by 125–250mg/day at 1- to 3-month intervals based on response and tolerance. If satisfactory remission achieved, continue at remission dose. If no improvement and no signs of serious toxicity after 2 to 3 months with doses of 500–750mg/day, may increase by 250mg/day at 2- to 3-month intervals until remission occurs or if toxicity develops. Discontinue if no improvement after 3 to 4 months with 1000–1500mg/day. Maintenance therapy: individualize; usual range 500–750mg/day; some may need less. Patients in remission for ≥6 months: reduce dose gradually in decrements of 125–250mg/day at approximately 3-month intervals. When surgery is contemplated: consider dose reduction to 250mg/day if effects on collagen and elastin made it advisable; delay restarting therapy until wound healing is complete. Management of exacerbations: see full labeling.

Children Dosage:

Not established.

DEPEN Contraindications:

During pregnancy, except for the treatment of Wilson’s disease or in certain patients with cystinuria. Nursing mothers. History of penicillamine-related aplastic anemia or agranulocytosis should not be restarted on penicillamine. Rheumatoid arthritis patients with a history or other evidence of renal insufficiency.

Boxed Warning:

Penicillamine toxicity.

DEPEN Warnings/Precautions:

Risk for aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture's syndrome, and myasthenia gravis; may be fatal. Risk for serious hematological and renal adverse reactions. Obtain routine urinalysis, WBCs with differential, hemoglobin, and direct platelet count every 2 weeks for at least the first 6 months and monthly thereafter. Bone marrow depression. Discontinue if WBC <3500/mm3 occurs. Withhold therapy if platelets <100,000/mm3, a progressive fall in either platelet or WBC count in 3 successive determinations occurs. Signs of membranous glomerulopathy leading to nephrotic syndrome; monitor closely if proteinuria and/or hematuria develops. Obtain LFTs every 6 months during therapy; and at least every 3 months during the 1st year for Wilson’s disease. Discontinue immediately if abnormal urinary findings associated with hemoptysis and pulmonary infiltrates on X-ray occur. Evaluate if pulmonary symptoms develop. Discontinue if pemphigus is suspected; or if late rash (on the trunk) with intense pruritus and is unresponsive to topical corticosteroid therapy, or drug eruption accompanied by fever, arthralgia, lymphadenopathy, or other allergic manifestations occur. Possible lupus erythematosus-like syndrome in certain patients with positive antinuclear antibody (ANA) test. In rheumatoid arthritis (with moderate degrees of proteinuria): obtain quantitative 24-hour urinary protein determinations at 1–2 week intervals (do not increase dosage); discontinue or reduce dose if proteinuria is >1g/24hrs or progressively increasing. In rheumatoid arthritis: discontinue therapy if unexplained gross hematuria, persistent microscopic hematuria, or drug fever (consider alternatives) develops. In Wilson’s disease or cystinuria: consider risks/benefits of continuing treatment in those with potentially serious urinary abnormalities. Withhold therapy if drug fever occurs until reaction subsides. Perform annual X-ray for renal stones in cystinuria. Penicillin allergy. May increase the amount of soluble collagen. Elderly. 

DEPEN Classification:

Chelating agent.

DEPEN Interactions:

Risk for serious hematologic and renal adverse reactions with gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone, or phenylbutazone: avoid. Increased risk of serious adverse reactions in those who discontinued gold salt therapy due to a major toxic reaction. Avoid mineral supplements in rheumatoid arthritis. May give iron supplement in short courses if needed but 2 hours should elapse between penicillamine and iron.

Adverse Reactions:

Anorexia, epigastric pain, nausea, vomiting, diarrhea, loss of taste perception, generalized pruritus, early and late rashes, pemphigus, drug eruptions, lupus erythematosus-like syndrome, urticaria, exfoliative dermatitis, thrombocytopenia, leukopenia, proteinuria, hematuria, CNS effects, dystonia, increased skin friability; rare: cheilosis, glossitis, gingivostomatitis, intrahepatic cholestasis, toxic hepatitis, obliterative bronchiolitis, thyroiditis, hypoglycemia, thrombophlebitis, hyperpyrexia.

Generic Drug Availability:

YES

How Supplied:

Tabs—100

Pricing for DEPEN

250mg tablet (Qty: 25)
Appx. price $500
GoodRx

Inborn errors of metabolism:

Indications for: DEPEN

Wilson’s disease: to minimize dietary intake and absorption of copper; or to promote excretion copper deposited in tissues.

Adults and Children:

Take on an empty stomach at least 1hr before meals or 2hrs after meals, and at least 1hr apart from any other drug, food, or milk. Determine dose based on measurement of 24-hour urinary copper excretion (greatest value in the 1st week of therapy) and free copper in serum. Adequately treated: usually <10mcg free copper/dL of serum. Give 0.75–1.5g/day for ~3 months (resulting in an initial 24-hour cupriuresis of >2mg). If 1g/day initially is not tolerated, may start with 250mg/day and increase gradually. Max: usually 2g/day. Supplement with pyridoxine 25mg/day; may also benefit from multivitamin preparation (copper-free). During pregnancy: limit to 1g/day; if cesarean section is planned, reduce to 250mg/day for the last 6 weeks of pregnancy and post-op until wound healing is complete. When surgery is contemplated: consider dose reduction to 250mg/day if effects on collagen and elastin made it advisable; delay restarting therapy until wound healing is complete.

DEPEN Contraindications:

During pregnancy, except for the treatment of Wilson’s disease or in certain patients with cystinuria. Nursing mothers. History of penicillamine-related aplastic anemia or agranulocytosis should not be restarted on penicillamine. Rheumatoid arthritis patients with a history or other evidence of renal insufficiency.

Boxed Warning:

Penicillamine toxicity.

DEPEN Warnings/Precautions:

Risk for aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture's syndrome, and myasthenia gravis; may be fatal. Risk for serious hematological and renal adverse reactions. Obtain routine urinalysis, WBCs with differential, hemoglobin, and direct platelet count every 2 weeks for at least the first 6 months and monthly thereafter. Bone marrow depression. Discontinue if WBC <3500/mm3 occurs. Withhold therapy if platelets <100,000/mm3, a progressive fall in either platelet or WBC count in 3 successive determinations occurs. Signs of membranous glomerulopathy leading to nephrotic syndrome; monitor closely if proteinuria and/or hematuria develops. Obtain LFTs every 6 months during therapy; and at least every 3 months during the 1st year for Wilson’s disease. Discontinue immediately if abnormal urinary findings associated with hemoptysis and pulmonary infiltrates on X-ray occur. Evaluate if pulmonary symptoms develop. Discontinue if pemphigus is suspected; or if late rash (on the trunk) with intense pruritus and is unresponsive to topical corticosteroid therapy, or drug eruption accompanied by fever, arthralgia, lymphadenopathy, or other allergic manifestations occur. Possible lupus erythematosus-like syndrome in certain patients with positive antinuclear antibody (ANA) test. In rheumatoid arthritis (with moderate degrees of proteinuria): obtain quantitative 24-hour urinary protein determinations at 1–2 week intervals (do not increase dosage); discontinue or reduce dose if proteinuria is >1g/24hrs or progressively increasing. In rheumatoid arthritis: discontinue therapy if unexplained gross hematuria, persistent microscopic hematuria, or drug fever (consider alternatives) develops. In Wilson’s disease or cystinuria: consider risks/benefits of continuing treatment in those with potentially serious urinary abnormalities. Withhold therapy if drug fever occurs until reaction subsides. Perform annual X-ray for renal stones in cystinuria. Penicillin allergy. May increase the amount of soluble collagen. Elderly. 

DEPEN Classification:

Chelating agent.

DEPEN Interactions:

Risk for serious hematologic and renal adverse reactions with gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone, or phenylbutazone: avoid. Increased risk of serious adverse reactions in those who discontinued gold salt therapy due to a major toxic reaction. Avoid mineral supplements in rheumatoid arthritis. May give iron supplement in short courses if needed but 2 hours should elapse between penicillamine and iron.

Adverse Reactions:

Anorexia, epigastric pain, nausea, vomiting, diarrhea, loss of taste perception, generalized pruritus, early and late rashes, pemphigus, drug eruptions, lupus erythematosus-like syndrome, urticaria, exfoliative dermatitis, thrombocytopenia, leukopenia, proteinuria, hematuria, CNS effects, dystonia, increased skin friability; rare: cheilosis, glossitis, gingivostomatitis, intrahepatic cholestasis, toxic hepatitis, obliterative bronchiolitis, thyroiditis, hypoglycemia, thrombophlebitis, hyperpyrexia.

Generic Drug Availability:

YES

How Supplied:

Tabs—100

Pricing for DEPEN

250mg tablet (Qty: 25)
Appx. price $500
GoodRx

Miscellaneous urogenital disorders:

Indications for: DEPEN

Cystinuria, when conventional treatments were inadequate to control recurrent stone formation.

Adults and Children:

Take on an empty stomach at least 1hr before meals or 2hrs after meals, and at least 1hr apart from any other drug, food, or milk. Drink plenty of fluids (1 pint at bedtime + 1 pint once during the night). Individualize a dose that limits cystine excretion to 100–200mg/day in those with no history of stones, and <100mg/day in those with stone formation and/or pain. Administer with conventional therapy. Adults: usually 2g/day, with a range of 1–4g/day. Pediatrics: 30mg/kg/day. Give in 4 equally divided doses; if not feasible, give a larger portion at bedtime. May initiate with 250mg/day and increase gradually. Supplement with pyridoxine 25mg/day; may also benefit from multivitamin preparation. When surgery is contemplated: consider dose reduction to 250mg/day if effects on collagen and elastin made it advisable; delay restarting therapy until wound healing is complete.

DEPEN Contraindications:

During pregnancy, except for the treatment of Wilson’s disease or in certain patients with cystinuria. Nursing mothers. History of penicillamine-related aplastic anemia or agranulocytosis should not be restarted on penicillamine. Rheumatoid arthritis patients with a history or other evidence of renal insufficiency.

Boxed Warning:

Penicillamine toxicity.

DEPEN Warnings/Precautions:

Risk for aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture's syndrome, and myasthenia gravis; may be fatal. Risk for serious hematological and renal adverse reactions. Obtain routine urinalysis, WBCs with differential, hemoglobin, and direct platelet count every 2 weeks for at least the first 6 months and monthly thereafter. Bone marrow depression. Discontinue if WBC <3500/mm3 occurs. Withhold therapy if platelets <100,000/mm3, a progressive fall in either platelet or WBC count in 3 successive determinations occurs. Signs of membranous glomerulopathy leading to nephrotic syndrome; monitor closely if proteinuria and/or hematuria develops. Obtain LFTs every 6 months during therapy; and at least every 3 months during the 1st year for Wilson’s disease. Discontinue immediately if abnormal urinary findings associated with hemoptysis and pulmonary infiltrates on X-ray occur. Evaluate if pulmonary symptoms develop. Discontinue if pemphigus is suspected; or if late rash (on the trunk) with intense pruritus and is unresponsive to topical corticosteroid therapy, or drug eruption accompanied by fever, arthralgia, lymphadenopathy, or other allergic manifestations occur. Possible lupus erythematosus-like syndrome in certain patients with positive antinuclear antibody (ANA) test. In rheumatoid arthritis (with moderate degrees of proteinuria): obtain quantitative 24-hour urinary protein determinations at 1–2 week intervals (do not increase dosage); discontinue or reduce dose if proteinuria is >1g/24hrs or progressively increasing. In rheumatoid arthritis: discontinue therapy if unexplained gross hematuria, persistent microscopic hematuria, or drug fever (consider alternatives) develops. In Wilson’s disease or cystinuria: consider risks/benefits of continuing treatment in those with potentially serious urinary abnormalities. Withhold therapy if drug fever occurs until reaction subsides. Perform annual X-ray for renal stones in cystinuria. Penicillin allergy. May increase the amount of soluble collagen. Elderly. 

DEPEN Classification:

Chelating agent.

DEPEN Interactions:

Risk for serious hematologic and renal adverse reactions with gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone, or phenylbutazone: avoid. Increased risk of serious adverse reactions in those who discontinued gold salt therapy due to a major toxic reaction. Avoid mineral supplements in rheumatoid arthritis. May give iron supplement in short courses if needed but 2 hours should elapse between penicillamine and iron.

Adverse Reactions:

Anorexia, epigastric pain, nausea, vomiting, diarrhea, loss of taste perception, generalized pruritus, early and late rashes, pemphigus, drug eruptions, lupus erythematosus-like syndrome, urticaria, exfoliative dermatitis, thrombocytopenia, leukopenia, proteinuria, hematuria, CNS effects, dystonia, increased skin friability; rare: cheilosis, glossitis, gingivostomatitis, intrahepatic cholestasis, toxic hepatitis, obliterative bronchiolitis, thyroiditis, hypoglycemia, thrombophlebitis, hyperpyrexia.

Generic Drug Availability:

YES

How Supplied:

Tabs—100

Pricing for DEPEN

250mg tablet (Qty: 25)
Appx. price $500
GoodRx