Rheumatoid arthiritis Wilsons disease Cystinuria

Penicillamine has a high incidence ofuntoward reactions, saomeofwhich are potentially fatal. Medical supervision throughout administration is mandatory.

CNS- tinnitus, myastenia gravis, polyradiculopathy (rare) , peripheral sonsory and neuropathies (including polyradiculopathy) Muscular weakness may not occur with peripheral neuropathies

GI- anorexia, epigastric pain, nausea, vomiting or occasional diarrhea, blunting diminution or total loss of taste perception, intrahepatic cholestatic and toxic hepatitis, cheilosis, glossitis, stomatitis

Hematologic- thrombocytopenia, leukopenia, bone marrow depression,sideroblastic anemia. Fatalities have resulted from thrombocytopenia , agranulocytosis, aplastic anemia

Hypersensitivity- generalised pruritus, early and late rashes, lupus erythematosus-like syndrome similar to other drug-induced lupus, drug eruptions

Renal- proteinuria or hematuria that may progress to the nephrotic syndrome as a result of immune complex membranous glomerulopathy.

Miscellaneous- Thrombophlebitis, hyperpyrexia, falling hair or alopecia, lichen planus, myasthenia gravis, nail disorders, mammary hyperplasia, toxic epidermal necrolysis, anetodema, fatal renal vasculitis

History of penicillamine-related aplastic anemia or agranucytosis, rheumatoid arthritis patients with a history of renal insufficiency

Special precautions:

Dietary supplementaion- becuase ofdietary restriction,give patients with WIlsons disease cystinuria, and rheumatoid arthritis , whose nurtion is impaired 25mg/day of pyridoxine during therapy as penicillamine increases the requirement for this vitamin.

Iron deficiency may develop especially in children and in menstruating women

Collagen and elastin- effects of penicillamine on collagen make it advisable to consider a reduction in dosage of 250mg/day when surgery is contemplated . Delay full therapy unril the wound healing is complete.

Monitoring- when indicated monitor drug toxicity or efficacy theough urinalysis. In rheumatoid arthiritis patients, discontinue the drug if unexplained gross hematuria or persistent microscopic hematuria develops.

Drug food interactions- The absorption of penicillamine is decreased by 52% when taken with food.

Warnings-

Fatalities- penicilamine has been associated withn fatalities due to aplastic anemia, agranulocytosis, thrombocytopenia, sideroblastic anemia, Goodpastures syndrome and myasthenia gravis

Hematologic- Leukopenia (2%), and thrombocytopenia (4%) have occurred. A platelet count below 100,000mm3 even in the absence of clinical bleeding or a pregressive fall in either platelet count or WBC in three successive determinations , even though the values are in the normal range , requires at least cessation of therapy.

Hepatotoxicity- peniciallamine has been associated with a mild elevation of hepatic enzymes that returns to normal even with continuarion of the drug.

Lupus erythematous- certain patients will develop a positive antineuclear antibody (ANA) test and some may show a lupus erythematosus-like syndrome similar to other drug induced lupus, but it is not associated with hypocomplementemia and may be present without neuropathy.

Oral ulcerations- may develop which may have the appearance of aphthous stomatis, this usually recurs on rechallenge but often clears on lower dosage Hypoglycemia- has been reported in four patients receiving penicillamine therapy for rheumatoid arthiritis. The mechanism of hypglycemia is unknown Autoimmune syndrome- which may be caused by penicillamine include polymyosotis, alveolitis and dermatomyosistis Cross sensitivity- may theorically appear in patients allergic to penicillin.

Hypersensitivity- allergic reactions occur 1/3rd of patients.They are more common at the start of treatment and occur as generalized rashes or drug fever.

Drug fever- may appear in some patients usually in the second to third week of therapy

Pregnancy- use only when clearly needed.

Lactaction- safety has not been established Children- the efficacy of penicillamine in juvenlie rheumatoid arthritis has not been established.

Indications:

Rheumatoid arthiritis Wilsons disease Cystinuria

Dosage:

Liquid- Throughly massage into the skin from to the soles of the feet. Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

Taste disturbances-

Drugs causing Adverse Reactions- ( 385 )

1. Penicillamine

2. Biguanidines

3. Griseofluvin

4. Metronidazole

5. Lithium

6. Rifampin

1. Take on an empty stomach, 1 hour before or 2 hours after mealsand at atleast 1 hour apart from any other drug food or milk.

2. Patients with cystinuria should drink large amounts of water.

3. Notify physician if skin rash, unusual brusing or bleeding, sore throat, exertional dyspnea, unexplained coughing/ wheezing, fever, chills, or other unusual effects occur.

4.Allergies- tell your doctor if you have ever had any unusual or allergic reaction to penicillin or penicillamine Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.

5.Pregnancy - penicillamine may cause birth defects if taken during pregnancy

6.Breast feeding- not known whether penicillamine passes into breast milk.

7. Children - no specific information comparing use of penicillamine in children . Not expected to cause different side effects or problems inchildfen than in adults.

8.Elderly- elderly are more sensitive than younger adults to some effects of penicillamine

9. Other medicines - Gold compounds or Phenylbutazone - thechance of side effects may be increased

10. Other medical problems - Tell your doctor if you have any other medical problems especially - Blood disease caused by penicillamine or Kidney disease - chance ofside effects may be increased

11. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

12. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

13. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

Pharmacology- Rheumatoid arthirits- the mechanision of action of penicillamine is not understood., although it appears to suppress disease activity. Penicillamine markedly lowers IgM rheumatoid factor , but produces no significant depression in absolute levels of serum immunoglobulins, it dosociates macroglobulins (rheumatoid factor )

Pharmacokinetics- It is well absorbed from the GI tract after oral administration ( 40 to 70%) , peak plasm alevels occur in 1 to 3 hours.

The absorption of penicillamine is decreased by 52% when taken with food. Give penicillamine on an empty stomach at least 1 hour before meals or 2 hours after meals and at least 1 hour apart from any other drug, food or milk.

Pregnancy- Use only when clearly needed. Lactation- Safety has not been established

Children- The efficacy of penicillamine in juvenlie rheumatoid arthritis has not been established.