DermaNic with Quadracin

This product contains iron.

Warning: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of the reach of children. In case of accidental overdose, call a doctor or poison control center immediately.

Extreme caution should be used when prescribing this product to patients with a history of liver disease, jaundice, diabetes and/or kidney disease. These patients, as well as patients with a history of heavy use of alcohol, gallbladder disease, gout, and/or stomach ulcers, should be monitored closely. Abnormal liver functions tests have been reported in persons taking high doses of niacin. Patients with coronary artery disease or unstable angina should not take niacin without their licensed medical practitioner's supervision, as large doses can increase the risk of heart rhythm problems. Caution is also advised in patients with low blood pressure as niacin may cause a dangerous drop in blood pressure. Niacin can be toxic to the liver at high doses. Do not exceed 3 grams per day of nicotinamide.1 Do not use other niacin-containing products while taking this product unless under the supervision of a licensed healthcare practitioner. This product is not formulated or intended to be used to treat hyperlipidemias. This product contains four different forms of niacin as Quadracin™, with the majority of the niacin being supplied in slowly metabolized forms, such as nicotinamide and inositol nicotinate. Nicotinamide does not have the same lipid modifying effects as nicotinic acid.

Caution is recommended in patients taking anticonvulsant medications as folate may interfere with anticonvulsant medication, and may lower seizure threshold. Furthermore, it has been reported that anticonvulsant medications interfere with folate metabolism, but the exact action is unclear; therefore caution is recommended with patients in this therapeutic group.

Patients undergoing cancer treatment should consult their licensed medical practitioner for advice. Before having surgery, tell your licensed medical practitioner that you are taking this product.

"Niacin flush" is a burning, tingling sensation in the face and chest, and red or flushed skin and is associated with rapidly metabolized niacin3. This reaction usually goes away as the body gets used to the medication. Other side effects of niacin include stomach upset, intestinal gas, dizziness, and pain in the mouth. Allergic reactions have been reported following the use of oral and parenteral folate. Mild transient diarrhea, polycythemia vera, itching, transitory exanthema and the feeling of swelling of the entire body has been associated with cobalamin. Call your medical practitioner about side effects. You may report side effects by calling 1-866-633-9033.

3 DermaNIC™ is formulated primarily with slowly metabolized niacin vitamers that present a lower risk of flushing than rapidly metabolized forms. Nevertheless, some patients may want to titrate slowly to the maintenance level as prescribed by a licensed medical practitioner.

IRON

DermaNIC™ supplies iron as pure amino acid iron-chelate, which provides pure elemental iron - an essential component in the formation of hemoglobin. Iron therapy is necessary in advanced folate supplementation due to interference between iron and folate metabolism.6 Sufficient amounts are required for effective erythropoiesis. The selection of a non-heme form of supplemental iron is also important because the heme carrier protein (HCP) has been demonstrated also to be a proton coupled folate transporter (PCFT).6 As a result, when dietary folate intake is high, as would be with the administration of DermaNIC™, heme iron transport can be sacrificed, leading to potential iron deficiency. Co-administering non-heme iron compensates for these potential metabolic imbalances. This proprietary form of iron is protected under US Patent No. 7,341,708.

COBALAMIN

Cobalamin is required for two important reactions: the conversion of methylmalonyl CoA to succinyl CoA, a Krebs cycle intermediate, and the conversion of homocysteine to methionine, a reaction in which the methyl group of methyltetrahydrofolate is donated to remethylate homocysteine.16 Many factors contribute to the cobalamin deficiency including diet, gastrointestinal pathology, autoimmune disease and medications.

BIOAVAILABILITY ENHANCER

Piperine is an alkaloid found naturally in plants, and may have bioavailability-enhancing activity for some nutritional substances and for some drugs.7

FOLATE

Folates are best known for reducing the incidence of fetal neural tube defects (NTDs).24-26 NTDs are congenital malformations produced by failure of the neural tube to form and close properly during embryonic development.17,25 During the first four weeks of pregnancy - when many women do not even realize that they have conceived, adequate maternal folate intake is essential to reduce the risk of NTDs. As the postnatal period approaches there is increased demand again for folate regardless of lactation status. Folate is involved in transformylation and methylation metabolism as well as - indirectly, succinylation metabolism (through the "methyl trap" hypothesis). Folate plays a central role in the formation of nucleic acid precursors, such as thymidylic acid and purine nucleotides, which are essential for nucleic acid synthesis and cell division. IOM/NAS (1998) noted that the evidence for a protective effect from folate supplements is much stronger than that for food folate.17 Other dietary ingredients are added to folate as cofactors, coenzymes and co-metabolites; in studies by Czeizel and Dudas (1992) and Berry et al. (1999), factors other than folate may affect the magnitude of risk reduction or participate in a co-protective effect with folate. The need for folate for methyl group biosynthesis may also increase with high niacin intake. The major pathway of metabolism of nicotinamide is by methylation in the liver to form N-methylnicotinamide via reaction with methionine (as a methyl donor) and ATP. As a result, high levels of niacin may interfere with the metabolism of methionine, which could lead to hyperhomocysteinemia. Increased folate intake may also confer a protective effect against folate depletion and subsequent hyperhomocysteinemia in acne patients taking antibiotics.18-20 Certain antibiotics may affect the absorption and metabolism of folate. Isotretinoin, for example, has been shown to decrease serum folic acid levels.18 Furthermore, studies have reported elevated plasma homocysteine in patients on isotretinoin as quickly as 45 days after beginning therapy.19 Isotretinoin may inhibit the activity of the cystathionine-beta-synthase enzyme, thereby impairing the conversion of homocysteine to cystathionine in the transsulfuration pathway. Furthermore, one of the most common antibiotic treatments for acne includes the Sulfa antibiotics - such as cotrimoxazole, that inhibits folic acid synthesis in bacteria. This highlights the importance of folic acid, or folate, rescue therapy as an adjunctive modality to be used in the treatment of acne alongside traditional acne drug therapy. Additionally, serum folate levels were decreased in post adolescent acne patients.23

The present form of folate in this product is:

FOLIC ACID as CitraFolic®4 is a novel, controlled-release delivery method to optimize absorption of folic acid. CitraFolic® uses proprietary technology to encapsulate conventional folic acid, along with citrates, in controlled-release pellets. CitraFolic® is unique from conventional folic acid in that it: 1.) complies with USP requirements for folic acid dissolution. Some studies indicate that dissolution failure - that is, the failure of conventional folic acid supplements to meet USP requirements for dissolution - is a significant, concerning problem.4 2.) includes buffers to adjust the pH in order to remain soluble in a high acid environment, such as the gastric environment. This is important because folic acid must remain soluble in the acidic environment of the stomach in order to be absorbed in the intestine. Studies show that solubility of conventional folic acid decreases with increased acidity.5 Folic acid is converted into functional, metabolically active coenzyme forms for use in the body (61 Fed. Reg. at 8759-60), and supplies the active folate substrate, THF (tetrahydrofolate).16,17,24-26 Because the folate is controlled release (enteric coating delays 20 minutes then not less than 90% of folate is dissolved according to United States Pharmacopeia (USP) specifications within 60 minutes), it is less likely to interfere with heme iron (hemoglobin-derived iron) absorption as the body's transport has a greater affinity for folic acid than for heme iron.6

1. Enteric coating creates an initial delayed release of approximately 20 minutes, non-pH-dependant, in order to aid in reducing first pass metabolism degradation, high-acidity environmental exposure and/or oxidation factors.
2. Citrates are dispersed in a 2:1 ratio of sodium citrate to citric acid in order to achieve optimum pH for folic acid dissolution as per USP specifications.
3. Folates are dispersed amongst the citrates in a 1:3 ratio of folic acid to citrates in order to reach maximum dissolution potential in variant mediums.

Note: The total folate-citrate matrix reaches 75% dissolution between the first 20 to 45 minutes, with over 90% folate dissolution achieved - as per USP, within 60 minutes.

4 CitraFolic® uses only DMF-approved manufacturers of folic acid.

The Federal Register Notices from 1971 to 1973 established that increased folate was proper therapy in megaloblastic anemias of tropical and nontropical sprue, nutritional origin, pregnancy, infancy and childhood.10-13 Folate metabolism can be affected by malabsorption issues which differ widely among population groups. The March 5, 1996 Federal Register Notice (61 FR 8760) states that "The agency concluded that the scientific literature did not support the superiority of any one source of folate over others, and that the data were insufficient to provide a basis for stating that a specific amount of folate is more effective than another amount."16 The actual amount and source of folate require a licensed medical practitioner's supervision to achieve a satisfactory maintenance level, and may exceed the 0.8 mg UL. The Federal Register Notice of August 2, 1973 (38 FR 20750) specifically states that "dietary supplement preparations are available without a prescription (21 CFR 121.1134). Levels higher than dietary supplement amounts are available only with a prescription. Oral preparations supplying more than 0.8 mg of folate per dosage unit would be restricted to prescription dispensing and that a dietary supplement furnishing 0.8 mg could be prescribed when a maintenance level of 0.8 mg per day was indicated. When clinical symptoms have subsided and the blood picture and/or CSF folate levels have become normal, a maintenance level should be used. Patients should be kept under close supervision and adjustment of the maintenance level made if relapse appears imminent. In the presence of alcoholism, hemolytic anemia, anticonvulsant therapy, or chronic infection, the maintenance level may need to be increased."11 However, once the level of active folate exceeds 0.8 mg - as prescribed dosages, then the product is no longer a medical food but a prescription dietary supplement regardless of pregnancy/lactation status in spite of the fact that folic acid - including reduced forms, may be added to medical foods as defined in section 5(b)(3) of the Orphan Drug Act (21 USC 360ee(b)(3)), or to food (21 CFR 172.345).14-15 In the Letter Regarding Dietary Supplement Health Claim for Folic Acid, Vitamin B6, and Vitamin B12 and Vascular Disease (Docket No. 99P-3029) dated November 28, 2000, FDA wrote "... high intakes of folate may partially and temporarily correct pernicious anemia while the neurological damage of vitamin B12 deficiency progresses. IOM/NAS (1998) set the UL for all adults of 1 mg per day because of devastating and irreversible neurological consequences of vitamin B12 deficiency, the data suggesting that pernicious anemia may develop at a younger age in some racial or ethnic groups, and the uncertainty about the extent of the occurrence of vitamin B12 deficiency in younger age groups (IOM/NAS, 1998)."16 Summary: This product is a dietary supplement product that - due to advanced folate levels, requires administration under the care of a licensed medical practitioner, and the most appropriate way to do that is to provide the product as prescription for pedigree reporting and safety monitoring. The ingredients, indication or claims of this product are not to be construed to be drug claims.

DermaNIC™ contains a high dose of niacin and is NOT recommended for pregnant and/or lactating women. However, DermaNIC™ can be administered to women of childbearing age.

DermaNIC™ is supplied as a scored, beige-colored, oval tablet debossed with "044" on one side, in bottles of 60 tablets, (Product Code728595-500-60). DermaNIC™ is also supplied to licensed healthcare practitioners as 1ct samples, 28595-500-99. DermaNIC™ may - under certain circumstances, be dispensed through a certified mail-order program so long as there is record of prescription AND confirmation that the patient is under licensed medical supervision.

7 This product is a prescription-folate with or without other dietary ingredients that - due to increased folate levels (AUG 2 1973 FR 20750), requires an Rx on the label because of increased risk associated with masking of B12 deficiency (pernicious anemia). Based on our assessment of the risk of obscuring pernicious anemia, this product requires licensed medical supervision, an Rx status, and a National Drug Code (NDC) - or similarly- formatted product code, as required by pedigree reporting requirements and supply-chain control as well as - in some cases, for insurance-reimbursement applications. This product is not an Orange Book (OB) rated product, therefore all prescriptions using this product shall be pursuant to State statutes as applicable.