Brand name: Artamin
Active ingredient (generic name): Penicillamine
Manufacturer: Sandoz
Importer: Behestan Darou
Pharmacotherapeutic group: Stable, non-physiologic amino acid
Pharmaceutical form: 250MG Capsule
Pharmacodynamic:
Penicillamine shows specific affinity to heavy metals with which it forms chelate complexes. These are water-soluble, non-toxic compounds, which can be excreted by the kidneys. Penicillamine converts poorly soluble cystine into readily soluble cysteine sulfide which is mainly excreted along renal pathways.
Pharmacokinetic:
About 2 thirds of the unbound penicillamine fraction are absorbed from the duodenum. Bioavailability may be reduced by concomitant food intake. Peak concentrations of unbound penicillamine show dose-dependence and are reached within 1 1/2 hours. While most of the drug is eliminated along renal pathways as inactive disulfide or mixed disulfide with cysteine, a minor fraction is converted to S-methyl penicillamine, which is excreted via the kidneys or metabolized in the liver. Unbound penicillamine has a dose dependent elimination half-life of 1-2 hours. Its mainly albumin (Serum, plasma and tissue protein) bound fraction is eliminated at a half-life of 3-4 days.
Therapeutic indication:
Penicillamine is used for rheumatoid arthritis, juvenile rheumatoid arthritis, symptomatic and asymptomatic Wilson’s disease, Cystinuria, cystinosis, heavy metal poisoning (copper, gold, lead, mercury, cobalt, and zinc), primary biliary cirrhosis, chronic active hepatitis, scleroderma and benign hyperglobulinemic purpura.
Dosage and administration:
Rheumatoid arthritis, scleroderma and hepatitis:
First 4 weeks: 150-250 mg daily
Second 4 weeks: 250-450 mg daily
Third 4 weeks: 300-600 mg daily
A maximum dose is 1000 mg daily
Juvenile rheumatoid arthritis:
Treatment should be started with a daily dose of 5-10 mg/kg by weight. This should be gradually increased to a maximal dose of 15-20mg/kg by weight. One improvement has occurred; this dose should be reduced to a maintenance level of 10-15mg/kg by weight.
Cystinuria:
1000mg/m2 body surface area daily
Adverse reaction:
Side effects can often be controlled by reducing the dose. Allergic reactions involving the skin and mucous membranes like morbilliform, urticarial and vesicular rashes, pruritus and facial edema may occur. Rare adverse reactions are fever, arthralgia, lymph node swelling, leucopenia, thrombocytopenia, agranulocytosis, aplastic anemia and eosinophilia.
Contraindication:
Hypersensitivity to Artamin, abnormalities of the hemopoietic system, renal disease, myasthenia gravis.
Pharmacokinetic interactions
Artamin should not be administered concomitantly with gold, antimalarials and phenylbutazone. In patients with rheumatoid arthritis the drug may be combined with corticosteroids.
Discontinuation of iron replacement therapy enhances the absorption of unbound penicillamine.
Special warnings:
Before and during penicillamine treatment the following laboratory tests must be ordered without exception:
- Erythrocyte sedimentation rate: at 4-weekly intervals
- Urinalysis and blood count: at 2-weekly intervals initially; at 4-weekly intervals during maintenance treatment. Treatment should be discontinued if the leukocyte count drops to less than 4000 mm3 and if the platelet count drops to less than 100000 mm3 . Eosinophilia of more than 6% necessitates dose reduction or interruption of treatment.
- Alkaline phosphatase: at 4-weekly intervals
- ANA: at 3-monthly intervals
In children urinalysis, blood count and ANA titers should be obtained at shorter intervals.
Caution should be exercised in patients with a history of confirmed severe penicillamine allergy (desensitization may be considered if penicillamine is vitally indicated, e.g. in patients with Wilson’s disease.)
Associated pyridoxine administration has been recommended. In patients with heavy metal poisoning simultaneous pyridoxine medication is mandatory.
Pregnancy and lactation:
Penicillamine should be discontinued during pregnancy.
Storage temperature:
Room temperature (15-25 C)
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