Vayarin™

Suggested/Recommended/Usage/Directions

Dosage and administration Usual dose is 2 capsules daily or as directed by a physician.

Storage

Storage Dispense and keep in original bottle. Store at up to 77(0)F (25(0)). Protect from light and moisture.

Formula re: Type

Description Vayarin is an orally administered prescription medical food for the clinical dietary management of certain lipid imbalances associated with ADHD in children.

Formula re: Contains

Vayarin capsules contain shellfish (krill). May contain soy and fish.

Formulation re: Does NOT Contain

Vayarin capsules do not contain sugar, lactose, yeast or gluten.

Formula re: Contains

Pharmacology Vayarin is composed of Lipirinen, a proprietary composition containing phosphatidylserine-omega-3, EPA enriched.

Formula re: Contains

Mechanism of action Omega-3 long chain polyunsaturated fatty acids (LC-PUFA) have an important role in brain and central nervous system development and functioning [1-4]. Decreased omega-3 fatty acids levels, mainly DHA and EPA, are associated with the occurrence of psychiatric, neurodegenerative, and other neurodevelopmental disorders such as dyspraxia, dyslexia, autism [3], peroxisolmal disorders [5], Alzheimer's disease [6], and ADHD [3]. Administration of phosphatidylserine (PS) enriched with omega-3 fatty acids was found to significantly increase DHA level in rat brains [7]. While the extract mechanism by which Vayarin exerts its effects is not fully understood, PS present in the mammalian nervous system, which is characterized by its substantial levels of omega-3 fatty acids, has been implicated in numerous membrane related functions, such as maintaining the integrity of cell membranes, cell excitability, cell-to-cell recognition and communication [8]. PS has been found to regulate key proteins in neuronal membranes, including sodium/calcium ATPase [9] and protein kinase C [10] which undertake crucial functions in diverse signal transduction pathways. Similarly, PS interacts with Raf-1 protein kinase to promote a cascade of reactions that are believed to be involved in cell survival [11]. Additionally, PS has been found to influence neurotransmitters activity, such as the release of acetylcholine, dopamine and noradrenaline [12, 13] and to increase brain glucose levels. Absorption an metabolism Following dietary ingestion of phospholipids, pancreatic digestive enzymes cleave specific fatty acids, leading to the formation of lysophospholipids that are absorbed by the mucosal cells of the intestine and could be reacylated into phospholipids [14]. The fatty acids released can be further used for triglyceride synthesis. Because of the high activity of decarboxylases in the mucosal cells, the majority of the PS in converted into other phospholipids, primarily to phosphatidylethanolamine [15]. The reacylated PS, phosphatidylethanolamine and other phospholipids enter the lymph and circulation, and are redistributed. Drug interactions PS can potentially interact with some anticholinergic and cholinergic medications. It is recommended to consult with a physician about Vayarin interactions that may apply to specific medical conditions.

Formula re: Contains

Vayarin is composed of Lipirinen, a proprietary composition containing phosphatidylserine-omega-3, EPA enriched.

General Statements: All Other Content

Chemical structure Schematic structure of one of the most abundant molecules present in Vayarin.

General Statements: All Other Content

Clinical experience [17. 18] Double-blind study Method: A 15-week, double-blind, placebo-controlled clinical trial was conducted witn 200 ADHD children randomized to receive either Vayarin or placebo (4 capsules/day). The effect of Vayarin was assessed by rating scales and questionnaires, including the Conners' parent (CRS-P) and teacher (CRS-T) rating scales and the child health questionnaire (CHQ). Results: 162 participants completed the study, of whom 147 were included in the efficacy analysis. Significant reduction in ADHD scores was detected in the CRS-P assessment. In addition, a significant beneficial effect was observed in the quality of life questionnaire (CHQ). Subgroup analysis of children with a hyperactive/impulsive behavior, as well as mood and behavior-dysregulation, revealed a more pronounced reduction in ADHD scores. Physician supervision

General Statements: All Other Content

Drug abuse Vayarin does not have any known abuse or withdrawal effects.

General Statements: All Other Content

Adverse events According to both the double-blind study and open-label extension, Vayarin was well tolerated. Children maintained good health throughout both study phases (30 weeks) and no major adverse events were noted by the study physicians. In the double-blind study, 13 adverse events (in 12 participants) were classified as possibly or probably treatment-related in the Vayarin group. These included 6 cases of gastrointestinal discomfort, one case each of atopic dermatitis, hyperactivity, tics, nausea, elevated serum glutamic oxaloacetic transaminase (SGOT) and two cases of tantrum episodes. In the placebo group, 5 adverse events (in 5 participants) were classified as possibly or probably treatment related. These included 4 cases of gastrointestinal discomfort and one case of headache. In the open-label extension, 7 adverse events, classified by the study physicians as possibly or probably treatment-related, were recorded. These included 4 cases of gastrointestinal discomfort, one case each of headache, insomnia and high triglyceride level.

General Statements: All Other Content

How supplied Available as hard shell capsules. Commercial product is supplied in bottles of 60 capsules. Commercial product (60 capsules) 75959-233-60 Use under medical/physician supervision. Sample product (4 capsules) 75959-233-04 Professional samples - not for sale.

General Statements: All Other Content

VAYA Pharma does not represent these product codes to be actual National Drug Codes (NDCs). NDC format codes are product codes adjusted according to standard industry practice to meet the formatting requirements of pharmacy and health insurance computer systems.

Brand IP Statement(s) re: (c), (TM), (SM)

Vayarin and Lipirinen are trademarks of Enzymotec Ltd. US Patents #7935365, #7968112, #5965413, #8052992, #8470345