Penicillamine Chloroquine

Systemic muscle damage, often associated with pain and discomfort, is a well known problem associated with specific drugs such as epsilon amino caproic acid (EACA), clofibrate, emetine, vincristine, chloroquine, D-penicillamine, and anabolic steroids. Notes on each of these drugs follow, but for a detailed discussion of drug-induced muscle damage refer to Argov and Mastaglia (1988) and Harris and Blain (1990). 

Only trained medical personnel can prescribe DMARDs like aura-nofin, but there are others such as chloroquine, methotrexate, penicillamine, and sulfasalazine. Chloroquine was originally developed as an antimalarial drug but was found to have some anti-rheumatic activity. Methotrexate acts on the immune system and was particular favoured by doctors for the treatment of arthritis in the 1990s because it could be prescribed on a long-term basis. Penicillamine is effective but needs to be taken for many months before its benefits appear. Sulfasalazine was specifically developed as an anti-rheumatic drug and... 

Gibson T, Emery P, Armstrong RD, Crisp AJ, Panayi GS. Combined D-penicillamine and chloroquine treatment of rheumatoid arthritis—a comparative study. Br J Rheumatol 1987 26(4) 279-84. 

Quinoline antimalarials such as hydroxychloroquine (Fig. 5-6) and chloroquine have been found to have antiarthritic properties however, the onset of clinical improvement, as with penicillamine and gold, takes months. Irreversible retinopathy, including retinal opacity, can be encountered. Lesser toxicities include skin pigmentation and alopecia. Proposals to possible mechanisms of action are speculative at best. It should be emphasized that none of the slow-action antiarthritic agents discussed earlier should be considered as initial therapy in RA. The salicylates and other NSAIDs deserve this distinction. If results are unsatisfactory gold may be considered as the subsequent therapeutic step. Penicillamine would be a logical alternate, as would short-term steroids or cytotoxic agents. 

The manufacturers say that the concurrent use of leflunomide and other DMARDs (they list azathioprine, chloroquine, hydroxychloroquine, intramuscular or oral gold and penicillamine) has not yet been studied but they say that combined use is not advisable because of the increased risk of serious adverse reactions (haemo- or hepatotoxicity). As the active metabolite of leflunomide has a long half life of 1 to 4 weeks the manufacturers say that a washout of colestyramine or activated charcoal should be given if patients are to be started on other DMARDs. See also Methotrexate, below. 

Penicillamine plasma levels are increased by chloroquine and an increase in penicillamine toxicity is possible. Penicillamine should not be used with gold. Indometacin slightly increases penicillamine levels, and its use with any NSAD) might increase the risk of renal damage. An isolated report describes penicillamine-induced breast enlargement in a woman taking a combined oral contraceptive. 

Studies in which chloroquine was given to patients taking penicillamine found that it was more effective, less effective, or indistinguishable from penicillamine alone. However in some instances penicillamine toxicity was reported to be increased. A pharmacokinetic study in patients with rheumatoid arthritis taking penicillamine 250 mg daily found that a single 250-mg dose of chloroquine phosphate increased the AUC by 34%, and raised the peak plasma levels by about 55%. It therefore seems possible that any increased toxicity is simply a reflection of increased plasma pen-... 

Indomethacin and chloroquine have been implicated in causing mild sensorimotor neuropathy as well as vascular myopathy. Peripheral neuropathy has been reported in patients treated with penicillamine, but less often than the myasthenic syndrome that develop in some patients treated with this drug. Paresthesiae and muscle weakness have been reported in some patients treated with phenylbutazone (Argov and Mastaglia 1979). In all these sydromes, little evidence exists that they are caused by allergic mechanisms. 

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