NICKEL: 96 Adverse Event Reports & Safety Profile

DESCRIPTION Acunol™ is a biochemical homeopathic medication indicated for the treatment of acne. 32-34 The active ingredients in each Acunol™ tablet consist of the following: Potassium Bromide (Kali Bromatum) 1X, Sodium Bromide (Natrum Bromatum) 1X, Zinc Sulphate (Zincum Sulphuricum) 1X, Sulphur 1X, and Nickel Sulphate (Niccolum Sulphuricum) 1X. These drug ingredients are listed in the Homoeopathic Pharmacopoeia of the United States (HPUS). 1 Inactive ingredients: Lactose, Magnesium Stearate, and Copper (II) Oxide. 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 ® ULTRA is indicated for the treatment of moderate to severe eczema, atopic dermatitis, seborrhea and seborrheic dermatitis. It has been found to work well with variety of combination therapies. Psoriasis also responds, but generally has a more favorable response to PSORIZIDE ® Forte (NDC 61480-255-05.)

DOSAGE AND ADMINISTRATION Take tablets twice a day (b.i.d.) for best results. Absorption of nickel sulphate is variable among individuals. For maximum nickel absorption, tablets should be taken orally upon rising at the beginning of the day and at the end of the day before bed. Take nothing but water for one hour after taking medication to aid nickel absorption. If taking Tetracycline or Levofloxacin allow at least two hours after taking Acunol. If taking a different Quinolone antibiotic, consult manufacturer's information. Kg lbs Starting dose Max Daily dose 23-45 51-100 ½ ∙ b.i.d. 1 ∙ b.i.d. 46-68 101-150 1 ∙ b.i.d. 2 ∙ b.i.d. 69-90 151-200 1½ ∙ b.i.d. 3 ∙ b.i.d. 91+ 201+ 2 ∙ b.i.d. 4 ∙ b.i.d. Increase dose only if needed on a monthly basis up to the max daily dose. Treatment dose and duration depends on the individual. In the setting of significant renal impairment Dosage should be adjusted and serum nickel and bromide levels should be followed. Steady state trough nickel 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 10-40 mcg/L. (Caution: post dose peak levels are unreliable.) Serum bromide assay by spectrophotometry is the historic standard. 36 Concentrations higher than 50 mg/dl may be compatible with toxicity. No therapeutic target levels exist for bromide.

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

ADVERSE REACTIONS PSORIZIDE ® ULTRA 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 or if there is a history of blistering hand eczema, 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) or if there is a history of vesicular hand eczema (dyshidrosis, pomphylox). Nickel allergy may be confirmed by a positive nickel patch test. Most patients with hand eczema, positive nickel allergy history, or a positive nickel patch test do not have any untoward reaction to administration of Acunol™. If there is a history of nickel sensitivity or dyshidrotic hand eczema, begin with a very low dose and slowly increase to a recommended starting dose over a period of 5 weeks as tolerated, thus allowing progressive GI absorption*. *Nickel desensitization schedule: Week Amount of Time to Take Medication Prior to Breakfast Week 1 With Breakfast Week 2 15 min Prior Week 3 30 min Prior Week 4 45 min Prior Week 5 and thereon 1 hour Prior If new pruritic rashes occur or persist, discontinue Acunol™ and treat appropriately. Do not use if there is a history of extra-cutaneous hypersensitivity to nickel or any ingredient in Acunol™ . Information for patients Patients using Acunol™ should receive the following information and instructions: This medication is to be used as directed by a physician. It is important to take orally at the beginning of the day on an empty stomach and at the end of the day before bed; take nothing but water for one hour afterwards to avoid interference with absorption. Drug interactions There are no known drug interactions. Since copper deficiency in human nutrition has occasionally been induced by supplemental zinc therapy, copper has been added in order to minimize this rare occurrence. (see Inactive ingredients )

For

Tetracycline or Quinolones co-administration with Acunol, see Dosage and Administration Carcinogenesis, mutagenesis, impairment of fertility No studies have been done on the carcinogenesis, mutagenesis, or impairment of fertility of Acunol™. No carcinogenesis or mutagenesis has been reported in multiple animal studies for oral administration of soluble nickel and bromide salts (active ingredients) even at very high doses. 10-14 Effects of soluble potassium bromide KBr is not listed as a carcinogen by the NTP, IARC, and OSHA. 16 Effects of sodium bromide NaBr is not listed as a carcinogen by the IARC, NTP, or OSHA. 35 Effects of zinc sulphate ZnSO 4 is not listed as a carcinogen by the ACGIH, IARC, NTP, or CA Prop 65. 29 Effects of sulphur Sulphur is not listed as a carcinogen by the ACGIH, IARC, NIOSH, NTP, or OSHA. 25 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 has never been known to induce carcinogenesis via any route of introduction including: oral, inhalation, cutaneous, IM, or IP. 10-12,15 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 per day Ni. 15 Pregnancy Pregnancy category C Animal reproduction studies have not been conducted with Acunol™. Acunol™ should not be given to a pregnant woman. Nursing mothers It is not known whether this drug is excreted in human milk. However, since many drugs are excreted in human milk, caution should be exercised when Acunol™ 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. Since copper deficiency in human nutrition has occasionally been induced by supplemental zinc therapy, copper has been added in order to minimize this rare occurrence. (see Inactive ingredients )

For

Tetracycline or Quinolones co-administration with Acunol, see Dosage and Administration

NICCOLUM METALLICUM 200CK HPUS Less than 10 -12 mg nickel per pellet Active ingredient**: See product name on front panel (contains 0.443 mg of the active ingredient per pellet).

lactose, sucrose