Penicillamine NSAIDs

The following drugs have been most often associated with erythema multiforme and Stevens-Johnson syndrome allopurinol, lamotrigine phenytoin, barbiturates, carbamazepine, estrogens/progestins, gold, NSAIDs, penicillamine, sulfonamides, tetracycline, and tolbutamide. 

On the other hand, probenecid increases the plasma level of acyclovir, allopurinol, barbiturate, benzodiazepines, clof-ibrate, dapsone, dyphylline, methotrexate, NSAIDs, penicillamine, sulfonylureas, and zidovudine. 

There is an increased risk of toxicity of MTX when administered with the NSAIDs, salicylates, oral antidiabetic drugs, phenytoin, tetracycline, and probenecid. There is an additive bone marrow depressant effect when administered with other drug known to depress the bone marrow or with radiation therapy. There is an increased risk for nephrotoxicity when MTX is administered with other drug that cause nephrotoxicity. When penicillamine is administered with digoxin, decreased blood levels of digoxin may occur. There is a decreased absorption of penicillamine when the dmg is administered with food, iron preparations, and antacids. 

Drugs that may be affected by NSAIDs include the following Aminoglycosides, anticoagulants, ACE inhibitors, beta blockers, cyclosporine, dextromethorphan, digoxin, dipyridamole, hydantoins, lithium, loop diuretics, methotrexate, penicillamine, potassium-sparing diuretics, sympathomimetics, theophylline, thiazide diuretics. 

Drugs that may be affected by probenecid include acyclovir allopurinol barbiturates benzodiazepines clofibrate dapsone dyphylline methotrexate NSAIDs pantothenic acid penicillamine rifampin sulfonamides sulfonylureas zidovudine salicylates. 

With the combination of traditional DMARDs complete remissions are obtained in 30% of early RA over a period of 5 years. These remissions last on average less than 10 months. After 5 years only half of the patients continue with MTX and less than 25% stay on other DMARDs. After 5 years non-compliance is mostly due to adverse effects and lack of efficacy of NSAIDs, hydroxychloroquine, sulfasalazine, prednisone, d-penicillamine, azafhio-prine, and gold salts. Only MTX retains some efficacy. With these therapeutic modalities joint erosions progress to permanent joint destruction, deformities and disability. 

Hepatitis with cholestasis Chlorpromazine, tricyclics, erythromycin, flucloxacillin, co-amoxiclav, ACE inhibitors, phenytoin, NSAIDs, ranitidine, propafenone, ketoconazole, azathioprine, gold salts, penicillamine... 

PENICILLAMINE ANALGESICS-NSAIDs t risk of nephrotoxicity Additive effect Monitor renal function closely... 

Additive renal toxic effects may occur with immunosuppressants (e.g. azathioprine, ciclosporin, tacrolimus), ACE inhibitors, penicillamine, irinotecan and aminoglycoside antibiotics. A deterioration of renal function may even occur after the topical use of NSAIDs. Guidelines are variable for the use of NSAIDs with differing degrees of renal function, as assessed by creatinine clearance measurements. 

Acute renal failure, e.g. cuninoglycosides, cisplatin Nephrotic syndrome, e.g. penicillamine, gold, cap-topril (only at higher doses than now recommended) Chronic renal failure, e.g. NSAIDs Functional impairment, i.e. reduced ability to dilute and concentrate urine (lithium), potassium loss in urine (loop diuretics), acid-base imbalance (acetazolamide). 

A clinical algorithm for the management of hematuria, for example in patients taking penicillamine or NSAIDs, has been published (238). It should be borne in mind that in such patients hematuria may be symptomatic of underlying pathology (for example a tumor of the urinary tract). 

Puromycin Cyclosporine A Penicillamine Heavy metals Hydrocarbons Colloidal gold/ gold salts NSAIDs Mitomycin C... 

Clinically important, potentially hazardous interactions with amphotericin B, benzodiazepines, doripenem, ertapenem, fludoxacillin, furosemide, glibenclamide, ketoprofen, ketorolac, methotrexate, NSAIDs, pemetrexed, penicillamine, penicillin G, penicillin V, salicylates, sulfamethoxazole, sulfonamides, torasemide, torsemide... 

A whole host of drugs can give rise to purpura, the most common being NSAIDs, thiazide diuretics, phenothiazines, cytostatics, gold, penicillamine, hydantoins, thiouracils, and sulfonamides. 

Lymphadenopathy may occur in patients with rheumatoid arthritis, particularly in nodes proximal to more actively involved joints. Renal involvement is rare but can be associated with treatment, including nonsteroidal anti-inflammatory drugs (NSAIDs), gold salts, and penicillamine. Amyloidosis is a rare complication of long-standing rheumatoid arthritis. It appears to be more common in Europe than in the United States. 

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. 

Furazolidone Metronidazole Minocycline Paromomycin Polymyxin B Salicylates and NSAIDs Loop diuretics Antitumor agents Miscellaneous Morphine Penicillamine Pentazocine Propranolol Propoxyphene... 

Indometacin has been found to increase the AUC of penicillamine by 26% and the peak plasma levels by about 22%. The UK manufacturer notes that use of NSAIDs may increase the risk of renal damage with penicillamine. The US manufacturer specifically recommends avoiding oxy-phenbutazone or phenylbutazone because these drugs are also associated with serious haematological and renal effects. Urinalysis for detection of haematuria or proteinuria should be regularly carried out in patients taking penicillamine. Be alert for evidence of toxicity if NSAIDs and penicillamine are used together. 

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