FUMARIC ACID: 13 Adverse Event Reports & Safety Profile

DESCRIPTION PSORIZIDE ® Forte is a biochemical homeopathic medication indicated for the treatment of contact dermatitis due to nickel (metal/jewelry allergy), dyshidrotic hand/foot eczema, and mild to severe psoriasis . 1-3 The active ingredients in each PSORIZIDE ® Forte tablet consist of the following: Fumaric Acid (Fumaricum Acidum) 1X, Potassium Bromide (Kali Bromatum) 1X, and Nickel Sulphate (Niccolum Sulphuricum) 1X. These drug ingredients are listed in the Homoeopathic Pharmacopoeia of the United States (HPUS). 4 Inactive ingredients: Lactose and Magnesium Stearate.

Pharmacological

Class: Homeopathic drug. Dosage form: Oral 600 mg scored tablet. May be swallowed whole, chewed or dissolved in the mouth and swallowed.

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.

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 )

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

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.

PRECAUTIONS Carefully adjust dosage to weight when treating young children. Use cautiously in setting of kidney disease. (see Dosage and Administration ) If skin rash appears or if nervous symptoms persist, recur frequently, or are unusual, discontinue use.

Hypersensitivity

Caution should be used when administering to patients with a history of contact sensitivity to nickel (common metal exposure). Nickel allergy may be confirmed by a positive nickel patch test. Most patients with positive nickel allergy history or a positive nickel patch test do not have any untoward reaction to administration of PSORIZIDE ® Forte. However, if there is a history of nickel sensitivity, begin with a very low dose and slowly increase over a period of six weeks as tolerated. Progressive G.I. absorption allows desensitization to occur. 8 Nickel desensitization schedule: Week Amount of Time to Take Medication Prior to Breakfast Week 1 1 tablet With Breakfast Week 2 1 tablet 15 min Prior Week 3 1 tablet 30 min Prior Week 4 1 tablet 45 min Prior Week 5 1 tablet 1 hour Prior Week 6 and thereon 2 tablets 1 hour Prior If new pruritic rashes occur or persist, discontinue PSORIZIDE ® Forte and treat appropriately. Do not use if there is a history of extra-cutaneous hypersensitivity to nickel or any ingredient in PSORIZIDE ® Forte. Information for patients Patients using PSORIZIDE ® Forte should receive the following information and instructions: This medication is to be used only as directed by a physician. It is important to take orally at the beginning of the day on an empty stomach (or any convenient time after having taken nothing but water for at least 7 hours) and to eat or drink nothing but water for one hour afterwards to avoid interference with absorption.

Drug Interactions

There are no known drug interactions. Carcinogenesis, mutagenesis, and impairment of fertility No studies have been done on the carcinogenesis, mutagenesis, or impairment of fertility of PSORIZIDE ® Forte. No carcinogenesis or mutagenesis has been reported in multiple animal studies for oral administration of fumaric acid and soluble nickel and bromide salts (active ingredients) even at very high doses. 24-27 Effects of fumaric acid It is not listed as a carcinogen by ACGIH, IARC, NIOSH, NTP, or OSHA. 26 It is a GRAS substance (generally recognized as safe) and is commonly used in food processing. Effects of soluble potassium bromide KBr is not listed as a carcinogen by the NTP, IARC, and OSHA. 28 Effects of soluble nickel sulphate Studies on experimental animals have never indicated that nickel, at any dose, is a carcinogen when introduced to the body orally. Furthermore, Nickel sulphate and other highly water soluble nickel salts, have never been known to induce carcinogenesis via any route of introduction including: oral, inhalation, cutaneous, IM, or IP. 10-12,27 No adverse effects were noted on fertility or reproduction in a 3-generational study of albino Wistar rats fed up to 1000 ppm Ni per day, which is equivalent to 50 mg/kg body weight per day Ni. 27 Pregnancy Pregnancy category C Animal reproduction studies have not been conducted with PSORIZIDE ® Forte. PSORIZIDE ® Forte should not be given to a pregnant woman. Nursing mothers It is not known whether this drug is secreted in human milk. However, since many drugs are secreted in human milk, caution should be exercised when PSORIZIDE ® Forte is administered to a nursing woman. Pediatric use Carefully adjust dosage to weight when treating young children.

Drug Interactions There are no known drug interactions.