Nickel Sulfate, Potassium Bromide, and Fumaric Acid

INDICATIONS PSORIZIDE ® Forte is indicated for the treatment of contact dermatitis due to nickel (metal/jewelry allergy,) dyshidrotic hand/foot eczema, and mild to severe psoriasis. It has been found to work well with a variety of combination therapies. Eczema, seborrhea and a variety of chronic pruritic inflammatory dermatoses generally respond well also.

DOSAGE AND ADMINISTRATION Absorption of nickel sulphate is variable among individuals . For maximum absorption, tablets should be taken orally at the beginning of the day (or any convenient time after having taken nothing but water for at least 7 hours). Take nothing but water for one hour after taking medication to aid absorption. Weight Starting Dose Max Daily Dose 40-80 lbs ½ tablet 1 ½ tablet 80-120 lbs 1 tablet 3 tablets 120-160 lbs 1 ½ tablets 4 ½ tablets 160-200 lbs 2 tablets 6 tablets 200-240 lbs 2 ½ tablets 7 ½ tablets Over 240 lbs 3 tablets 9 tablets In the setting of renal impairment Dosage should be adjusted and serum nickel and bromide levels should be followed. Steady state trough level should be drawn prior to ingesting the day's dose after one week of dosing or at appropriate intervals. Target trough serum nickel level is 30-60 mcg/L. (Caution: post dose peak levels are unreliable.) Maintenance phase In order to maintain symptomatic relief, medication may be continued at the same or reduced initial phase dose level. Treatment duration depends on the individual. For allergic nickel dermatitis, continue 2 tablets 1 hour prior to breakfast for weeks 7 – 16. (Refer to Hypersensitivity section above). Some patients may require continued or intermittent repeated treatment to maintain nickel desensitization.

WARNING Do not use if imprinted seal under bottle cap is missing or broken. Do not use if pregnant or nursing. If allergic to nickel or metal objects such as jewelry, see PRECAUTIONS for hypersensitivity information. Lactose intolerant patients may have gastrointestinal difficulty. This has very rarely been reported at the doses used.

CONTRAINDICATIONS Although there are no known contraindications, patients who are allergic to any PSORIZIDE ® Forte ingredient should consult a physician prior to taking the medication. (Refer to Section on Hypersensitivity )

Drug Interactions There are no known drug interactions.

ADVERSE REACTIONS PSORIZIDE ® Forte contains low doses of active ingredients. Therefore there are minimal known side effects. (see PRECAUTIONS for hypersensitivity information)

CLINICAL PHARMACOLOGY The active ingredients in PSORIZIDE ® Forte are simple biochemical compounds. The exact mechanism of action is unknown; however, it is believed PSORIZIDE ® Forte addresses a primary genetic biochemical defect. 5 FUMARIC ACID is a naturally occurring four carbon organic acid important in the Krebs cycle. This biochemical pathway is of central importance to energy production. Each tablet contains approximately 30 mg fumaric acid (calculated). Fumaric Acid has many uses, including use as a food additive (GRAS) and as a chelating agent. 13 The use of fumaric acid and its derivatives (esters) as a treatment for psoriasis is increasing worldwide. 14-20 Very little is known about its clinical pharmacology; however, dose dependant inhibitory effects on keratinocyte proliferation have been demonstrated. 16,21 POTASSIUM BROMIDE dissolves and dissociates in the digestive tract into its ionic constituents. Each tablet contains approximately 15 mg bromide (calculated). Ionic bromide is rapidly and completely absorbed from the intestine and distributed almost exclusively into the extracellular fluids. 11,12 Bromide is eliminated by the kidneys and the elimination half-life is 11-12 days. "Once a day" dosing will lead to a steady state concentration in about seven weeks. 11 NICKEL SULPHATE dissolves and dissociates in the digestive tract into its ionic constituents. Each tablet contains approximately 1.0 mg of ionic nickel (calculated). According to studies, 15% to 50% of ionic nickel is absorbed on a fasted stomach. 6 Food markedly decreases the rate and extent of nickel absorption. 7,8 Clinical studies show that serum concentrations of nickel are variable among patients after administering the same dose. 9 Peak serum nickel concentration is reached about two hours after oral administration. "Once a day" dosing leads to steady state serum concentrations in approximately one week. Nickel is in its highly stable divalent cation state and is therefore not expected to be metabolized to any significant degree in the body. Absorbed nickel is primarily excreted in the urine and elimination half-life is about 21 hours. 7,9 Renal clearance is rapid and efficient, and nickel does not accumulate in the body. 10