Psorizide® Forte

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.

De Sensitization Dosage & Administration:

12 Week Dosing Schedule – Once A Day Dosing (QD) Not weight dependent, all patients take the same dose:
• Week 1: Take 1 Tablet Each Morning With Breakfast for 7 days (must be taken with food)
• Week 2: Take 1 Tablet Each Morning With Water (no coffee, juice, etc.) 15 minutes before breakfast for 7 days
• Week 3: Take 1 Tablet Each Morning With Water 30 minutes before breakfast for 7 days
• Week 4: Take 1 Tablet Each Morning With Water 45 minutes before breakfast for 7 days
• Week 5: Take 1 Tablet Each Morning With Water 60 minutes before breakfast for 7 days
• Week 6: Take 2 Tablets Each Morning With Water 60 minutes before breakfast for 7 days
• Weeks 7 – 12: Take 2 Tablets Each Morning With Water 30 – 60 minutes before breakfast every day for 6 Weeks. At this point, skipping food is okay. PATIENT MAY BEGIN TO WEAR COSTUME JEWELRY AND OTHER METAL OBJECTS AGAIN.

These dosing instructions must be followed carefully. From Week 1 – Week 6, every dose MUST be taken in relation to food as above (within +/- five minutes). Extremely nickel sensitive patients could develop a red itchy rash if dosed inappropriately.

For those patients extremely hypersensitive to nickel, who develop a red itchy rash upon taking oral nickel, discontinue and treat appropriately. These patients in large part will still be able to be de- sensitized. Once skin rash is clear, begin ½ tablets for 14 days with breakfast. Continue with the schedule as above, except switch from 1 Week to 2 Week increments. After week 12, continue with week 12 dose for 6 more weeks. Long term treatment is required by some patients. Others will need intermittent therapy.

Absorption of nickel sulphate is variable among individuals.

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).

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

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 in the extracellular fluids. Bromide is eliminated by the kidneys and the elimination half-life is 11 -12 days. “Once A Day” (QD) dosing will lead to a steady state concentration in about seven weeks.

Fumaric Acid is a naturally occurring four carbon organic acid important in the Kerbs 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. Very little is known about its clinical pharmacology; however, dose dependent inhibitory effects on keratinocyte proliferation have been demonstrated.

Nickel Sulphate dissolves and dissociates in the digestive tract into its ionic constituents. Each tablet contains approximately 1.5 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 dosage. Peak serum nickel concentration is reached about two hours after oral administration. “Once A Day” (QD) 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:

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.

Pregnancy: Pregnancy category C. Animal reproduction studies have not been conducted. Psorizide® Forte 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 administered to a nursing mother.

General precautions: Use cautiously in setting of kidney disease (see dosage & administration section).

If skin rash appears or if nervous symptoms persist, recur frequently, or are unusual, discontinue patient use.

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.

Drug interactions: There are no known drug interactions.

Carcinogenesis, mutagenesis, impairment of fertility: No studies have been done on the carcinogenesis, mutagenesis, or impairment of fertility. 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.

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 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-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.

Effects of soluble potassium bromide: KBr is not listed as a carcinogen by the NTP, IARC, and OSHA.

Adverse reactions: Psorizide® Forte contains low doses of active ingredients; therefore there are minimal known side effects.

Over dosage: Potassium bromide toxicity: Indications of toxicity due to oral over dosage of bromide may include nausea, vomiting, apathy, and 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 1000 mg. This level is 67 times the dose received in one tablet.

Sulphur toxicity: The oral rat LS50 for Sulphur is reported to be greater than 5,000 mg/kg. This is more than 37,000 times the maximum dose recommended (see dosage). Ingestion of toxic levels of Sulphur can cause sore throat, nausea, headache, gastrointestinal irritation, and possibly unconsciousness in severe cases. Sulphur poses such a remote risk that it is placed in the lowest toxic category possible, EPA Toxicity Category IV.

Nickel sulphate toxicity: The oral rat LS50 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 are approximately 8 mg nickel/kg body weight. This is 180 times the maximum dose recommended for Psorizide® Forte.