PSORIZIDE® Forte

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

How Supplied: Scored tablets, off white in color with green speckles, with LL imprinted on one side and a score on the other, in child-resistant and tamper-resistant bottles of 90 tablets.

Dosage & Administration:

Take tablet(s) Once per Day. Dosage is weight dependent. Absorption of nickel sulphate is variable among patients. For maximum nickel absorption, tablets should be taken orally at the beginning of the day (or any other time after having taken nothing but water for at least 7 hours). To continue to aid maximum absorption, patient should ingest nothing but water for one hour after taking.

Maintenance phase: In order to maintain symptomatic relief, medication may be continued at the same or reduced Starting Dose level. Treatment duration depends on the individual.

Psorizide® Forte may interfere with the effects of oral antibiotics by reducing their absorption. If a patient is taking Tetracycline Antibiotics, allow at least two (2) hours after taking Psorizide® Forte before taking a Tetracycline Antibiotic. If a patient is taking Quinolone Antibiotics, allow at least six (6) hours after taking Psorizide® Forte before taking a Quinolone Antibiotic.

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). Treatment duration depends on the individual. Increase dose as needed on a monthly basis. Try b.i.d. dosing (upon rising and at bedtime) if max. dose (see above) is not effective, do not exceed max daily dose.

The active ingredients in Psorizide®Forte are simple biochemical compounds. The exact mechanism of action is unknown; however, it is believe Psorizide®Forte addresses a primary genetic biochemical defect.

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 and its derivatives. Very little is known about its clinical pharmacology; however, dose dependent inhibitory effects on keratinocyte proliferation have been demonstrated.

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. 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.

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. Food markedly decreases the rate and extent of nickel absorption. Clinical studies show that serum concentrations of nickel are variable among patients after administering the same dose. 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. Renal clearance is rapid and efficient, and nickel does not accumulate in the body.

PRECAUTIONS:

General Precautions: Use cautiously in setting of kidney disease (see dosage & administration).
If skin rash appears or if nervous symptoms persist, recur frequently, or are unusual, discontinue use.
Lactose Intolerant patients may have gastrointestinal difficulty. This has very rarely been reported at the doses used.
Pediatric Patients: Carefully adjust dosage to weight when treating young children.
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).
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.
Pregnancy: Pregnancy category C. Animal reproduction studies have not been conducted with Psorizide® Forte. Psorizide® Forte should not be given to a pregnant woman.

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 (dyshidrotic, 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 Psorizide® Forte. 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.

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.

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.

Effects of fumaric acid: It is not listed as a carcinogen by ACGIH, IARC, NIOSH, NTP, or OSHA. 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. 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. No adverse effects were noted on fertility or reproduction in a 3-general 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.

Adverse Reactions: Psorizide® Forte contains low doses of active ingredients. Therefore there are minimal known side effects. (See Precautions for hypersensitivity information).

OVERDOSAGE: Fumaric acid toxicity: The oral rat LD50 is 9300 mg/kg. This is 3800 times the maximum dose recommended for Psorizide® Forte. Potassium bromide toxicity: Indications of toxicity due to oral over dosage of bromide may include nausea and vomiting, apathy, disturbed coordination, loss of memory, drowsiness, and loss of emotional control, agitation, hallucination, tremors, depressed reflexes, stupor and coma. Acute toxic reactions in humans have been reported at doses as low as 1000mg. This level is 67 times the dose received in one tablet of Psorizide® Forte. Nickel sulphate toxicity: The oral rat LD50 for nickel sulphate hexahydrate is 275 mg/kg. Symptoms of toxicity due to oral over dosage of nickel sulphate may include nausea, vomiting, abdominal discomfort, diarrhea, giddiness, lassitude, headaches, cough and shortness of breath. The lowest observed transitory toxic effects from human ingestion of soluble nickel salts is approximately 8 mg nickel/kg body weight. This is 138 times the maximum dose recommended for Psorizide® Forte.