From the Guidelines
Penicillamine should be dosed at 750-1500 mg/day, administered in two or three divided doses, for the treatment of high copper levels in conditions such as Wilson's disease, as this dosing regimen has been shown to effectively promote urinary excretion of copper and reduce copper accumulation in tissues 1.
Key Considerations for Penicillamine Dosing
- The medication should be taken on an empty stomach, at least 1 hour before or 2 hours after meals, to maximize absorption, as food can decrease bioavailability by about 50% 1.
- Dosing in children should be 20 mg/kg/day, rounded off to the nearest 250 mg, and given in two or three divided doses 1.
- Pyridoxine (vitamin B6) supplementation at 25-50 mg/day is recommended during penicillamine therapy to prevent deficiency, as penicillamine can interfere with pyridoxine action 1.
Monitoring and Side Effects
- Regular monitoring of copper levels, liver function, complete blood count, and urinalysis is essential during treatment to assess the effectiveness of therapy and potential side effects.
- Common side effects include rash, loss of taste, nausea, and fever, while more serious adverse effects can include bone marrow suppression, autoimmune conditions, and kidney damage.
- Adequacy of treatment can be monitored by measuring 24-hour urinary copper excretion, which should be in the range of 200-500 µg (3-8 µmol) per day on chronic treatment 1.
From the FDA Drug Label
In all patients receiving penicillamine, it is important that penicillamine capsules be given on an empty stomach, at least one hour before meals or two hours after meals, and at least one hour apart from any other drug, food, or milk. Optimal dosage can be determined by measurement of urinary copper excretion and the determination of free copper in the serum. The urine must be collected in copper-free glassware, and should be quantitatively analyzed for copper before and soon after initiation of therapy with penicillamine capsules Determination of 24-hour urinary copper excretion is of greatest value in the first week of therapy with penicillamine. In the absence of any drug reaction, a dose between 0.75 and 1. 5 g that results in an initial 24-hour cupriuresis of over 2 mg should be continued for about 3 months, by which time the most reliable method of monitoring maintenance treatment is the determination of free copper in the serum. This equals the difference between quantitatively determined total copper and ceruloplasmin copper Adequately treated patients will usually have less than 10 mcg free copper/dL of serum. It is seldom necessary to exceed a dosage of 2 g/day.
The recommended dosing for high copper (Wilson’s Disease) is:
- Initial dose: 0.75 to 1.5 g/day
- Target 24-hour cupriuresis: over 2 mg
- Maintenance dose: usually less than 2 g/day
- Monitoring: 24-hour urinary copper excretion and free copper in the serum 2
From the Research
Penacillamine Dosing for High Copper
- The dosing of penacillamine for high copper levels in Wilson's disease is typically in the range of 15-25 mg/kg daily in the early stages of treatment 3.
- It is recommended to administer penacillamine more than 2 hours before meals 3.
- The use of penacillamine may be associated with undesirable or serious side-effects, such as systemic lupus erythematosus (SLE) and nephrotic syndrome, in 20-25% of all patients 3.
- In cases where penacillamine has to be withdrawn due to side-effects, trientine may be used as an alternative, with doses of 40-50 mg/kg daily 3.
- The treatment of Wilson's disease with penacillamine or other copper-chelating agents should be tailored to the individual patient's needs, taking into account factors such as medication side effects, patient comorbidities, and costs 4.
- Regular monitoring of liver enzymes and 24-hour urine copper levels is necessary to assess treatment efficacy and adjust dosing as needed 4, 3.