Chemistry - A monothiol chelating agent that is a degradation product of penicillins, penicillamine occurs as a white or practically white, crystalline powder with a characteristic odor. Penicillamine is freely soluble in water and slightly soluble in alcohol and has pKa values of 1.83, 8.03, and 10.83. Penicillamine may also be known as D-Penicillamine , beta,beta-Dimethylcysteine, or D-3-Mercaptovaline .
Storage/Stability/Compatibility - Penicillamine should be stored at room temperature (15-30°C). The capsules should be stored in tight containers and the tablets in well-closed containers.
Pharmacology - Penicillamine chelates a variety of metals, including copper, lead, iron, and mercury, forming stable water soluble complexes that are excreted by the kidneys.
Penicillamine also combines chemically with cystine to form a stable, soluble complex that can be readily excreted.
Penicillamine has antirheumatic activity. The exact mechanisms for this action are not understood, but the drug apparently improves lymphocyte function, decreases IgM rheumatoid factor and immune complexes in serum and synovial fluid.
Although penicillamine is a degradation product of penicillins, it has no antimicrobial activity.
Uses/Indications - Penicillamine is used primarily for its chelating ability in veterinary medicine. It is the drug of choice for Copper storage-associated hepatopathies in dogs, and may be used for the long-term oral treatment of lead poisoning or in cystine urolithiasis.
Although the drug may be of benefit in chronic hepatitis, doses necessary for effective treatment may be too high to be tolerated.
Pharmacokinetics - Penicillamine is well absorbed after oral administration and peak serum levels occur about one hour (in humans) after dosing. The drug apparently crosses the placenta, but otherwise little information is known about its distribution. Penicillamine that is not complexed with either a metal or cystine is thought to be metabolized in the liver and excreted in the urine and feces.
Contraindications/Precautions/Reproductive Safety - Penicillamine is contraindicated in patients who have a history of penicillamine-related blood dyscrasias.
Penicillamine has been associated with the development of birth defects in offspring of rats given 10 times the recommended dose. There are also some reports of human teratogenicity.
Adverse Effects/Warnings - In dogs, the most prevalent adverse effect associated with penicillamine is nausea and vomiting. If vomiting is a problem, attempt to alleviate by giving smaller doses of the drug on a more frequent basis. Although food probably decreases the bioavailability of the drug, many clinicians recommend mixing the drug with food or giving at mealtimes if vomiting persists. Although thought to occur infrequently or rarely, fever, lymphadenopathy, skin hypersensitivity reactions, or immune-complex glomerulonephropathy may also potentially occur.
Overdosage/Acute Toxicity - No information located.
Drug Interactions - The amount of penicillamine absorbed from the GI tract may be reduced by the concurrent administration of food, antacids, or iron salts. Administration of penicillamine with gold compounds, cytotoxic or other immunosuppressant agents (e.g., cyclophosphamide, azathioprine, but not corticosteroids), or phenylbutazone may increase the risk of hematologic and/or renal adverse reactions. Concomitant administration with 4-aminoquinoline compounds (e.g., chloroquine, quinacrine) may increase the risks of severe dermatologic adverse effects occurring. Penicillamine may cause pyridoxine deficiency in humans, but this is not believed to occur in dogs.
Drug/Laboratory Interactions - When using technetium Tc 99m gluceptate to visualize the kidneys, penicillamine may chelate this agent and form a compound which is excreted via the hepatobiliary system. This may result in gallbladder visualization which could confuse the results.
For copper-associated hepatopathy:
a) 10 - 15 mg/kg PO bid on an empty stomach. Only effective for long-term use, not for acute copper toxicity. (Twedt and Whitney 1989)]
b) For Bedlington Terriers: Initially at 125 mg q12h PO. If anorexia and vomiting are significant problems, start dose at 125 mg daily and increase to 125 mg bid over several days. (Hardy 1989)
c) 125 - 250 mg PO 30 minutes prior to feeding. If vomiting occurs, divide daily dosage into bid-tid. (Cornelius and Bjorling 1988)
For cystine urolithiasis:
a) 15 mg/kg PO twice daily. If nausea and vomiting occur, mix with food or give at mealtime. Some dogs may need to have the dosage slowly increased to full dose in order to tolerate the drug. (Osborne, Hoppe, and O'Brien 1989)
b) 15 mg/kg PO bid with food (Lage, Polzin, and Zenoble 1988)
For lead poisoning:
a) After initial therapy regimen with CaEDTA and if continued therapy is desired at home, may give penicillamine at 110 mg/kg/day PO divided q6-8h for 1-2 weeks. If vomiting, depression, and anorexia occur, may reduce dose to 33 - 55 mg/kg/day divided q6-8h which should be better tolerated. (Mount 1989)
b) As an alternate or adjunct to CaEDTA: 30 - 110 mg/kg/day divided qid for 7 days; may repeat after 7 days off therapy. If vomiting occurs, may give dimenhydrinate at 2 - 4 mg/kg PO 1/2 hour before penicillamine dose. (Grauer and Hjelle 1988b)
For lead poisoning:
a) After initial therapy with CaEDTA and if blood lead is greater than 0.2 ppm at 3-4 weeks post-treatment, may repeat CaEDTA or give penicillamine at 125 mg q12h PO for 5 days. (Reid and Oehme 1989)
Monitoring Parameters - Monitoring of penicillamine therapy is dependent upon the reason for its use; refer to the references in the Dose section above for further discussion on the diseases and associated monitoring of therapy.
Client Information - This drug should preferably be given on an empty stomach, at least 30 minutes before feeding. If the animal develops problems with vomiting or anorexia, three remedies have been suggested. 1) Give same total daily dose, but divide into smaller individual doses and give more frequently. 2) Temporarily reduce the daily dose and gradually increase to recommended dosage. 3) Give with meals (will probably reduce amount of drug absorbed).
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Veterinary-Approved Products: None
Penicillamine Oral Titratable Tablets 250 mg (scored); Depen® (Wallace); (Rx)
Penicillamine Oral Capsules 125 mg, 250 mg; Cuprimine® (Merck) (Rx)
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