Levomefolate Calcium Acetylcysteine and Mecobalamin Algal

Virtus Pharmaceuticals

Levomefolate Calcium*/Acetylcysteine/Mecobalamin/Algal Powder(6 mg-600 mg-2 mg-90.314 mg)

FULL PRESCRIBING INFORMATION: CONTENTS*

• LEVOMEFOLATE CALCIUM ACETYLCYSTEINE AND MECOBALAMIN ALGAL INDICATIONS AND USAGE:
• REFERENCES:
• PRINCIPAL DISPLAY PANEL - 90 Tablet Bottle Label

FULL PRESCRIBING INFORMATION

Prescription Vitamin B₉-Containing Dietary Supplement

R_x

DESCRIPTION: Levomefolate Calcium/Acetylcysteine/Mecobalamin/Algal Powder (6 mg-600 mg-2 mg-90.314 mg) is an orally administered prescription dietary supplement, and should be administered under the supervision of a licensed medical practitioner.

INGREDIENTS: This product contains the following dietary ingredients:

Other Ingredients: Silicified Microcrystalline Cellulose NF, Polyvinyl Alcohol, Croscarmellose Sodium NF, Titanium Dioxide, Polyethylene Glycol 3350, Magnesium Stearate (NF, Vegetable Source), Talc, Beet Powder Red (color), Caramel FCC (color), Carnauba Wax.

CAUTION: Contains milk (caseinate) and soy. Does NOT contain lactose, yeast or gluten.

If you are pregnant or nursing a baby, please ask a health professional.

KEEP THIS OUT OF REACH OF CHILDREN. This product is not recommended for use in children under the age of twelve.

All prescriptions using this product shall be pursuant to state statutes as applicable. This is not an Orange Book product.

INDICATIONS AND USAGE:

Levomefolate Calcium/Acetylcysteine/Mecobalamin/Algal Powder (6 mg-600 mg-2 mg-90.314 mg) is indicated for the distinct nutritional requirements of patients in need of advanced vitamin B₉ supplementation-specifically suboptimal vitamin B₉ or maintenance-level needs, as determined by a licensed medical practitioner.

DOSAGE AND ADMINISTRATION: Usual adult dose is one caplet daily or as prescribed by a licensed medical practitioner.

Store at controlled room temperature 15°-30°C (59°-86°F). [See USP]. Protect from light and moisture. Dispense in a tight, light-resistant container. Notice: Contact with moisture may produce surface discoloration or erosion.

Call your medical practitioner about side effects. You may report side effects by calling 813-283-1344.

VITAMIN B₉ REGULATION: The Federal Register Notices from 1971 to 1973 established that increased vitamin B₉ was proper therapy in megaloblastic anemias of tropical and nontropical sprue, nutritional origin, pregnancy, infancy and childhood. Vitamin ₉ 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 vitamin B₉ over others, and that the data were insufficient to provide a basis for stating that a specific amount of vitamin B₉ is more effective than another amount [emphasis added]." The actual amount and source of vitamin B₉ 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 vitamin B₉ 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 vitamin B₉ 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 [emphasis added].” However, once the level of active vitamin B₉ exceeds 0.8 mg - as prescribed dosages, then the product is no longer a medical food but a dietary management / prescription (R_x)-vitamin B₉ 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). 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 vitamin B₉ 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) [emphasis added].” Summary: This product is a dietary management product that - due to advanced vitamin B₉ 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.

REFERENCES:

VITAMIN B₉ MECHANISM OF ACTION: Vitamin B₉ is essential for the production of certain coenzymes in many metabolic systems such as purine and pyrimidine synthesis. It is also essential in the synthesis and maintenance of nucleoprotein in erythropoiesis. It also promotes white blood cell (WBC) and platelet production in vitamin B9-deficiency anemia. Vitamin B₉ is associated with methylation and transformylation biochemistry.

INTERACTIONS: Talk to your healthcare practitioner and/or pharmacist before taking or using any prescription or over-the-counter medicines or herbal/health supplements alongside this product.

ADVERSE REACTIONS: Allergic reactions have been reported following the use of oral and parenteral vitamin B₉. Mild transient diarrhea, polycythemia vera, itching, transitory exanthema and the feeling of swelling of the entire body has been associated with cobalamin. Nausea, vomiting, diarrhea, transient skin rash, flushing, epigastric pain, and constipation have been associated with acetylcysteine.

Call your medical practitioner about side effects.

CONTRAINDICATIONS: This product is contraindicated in patients with a known hypersensitivity to any of the components contained in this product.

WARNINGS: Caution is recommended in patients with a history of bipolar illness. Mood elevation is possible in this population.

Caution is also recommended in patients taking anticonvulsant medications as vitamin B₉ may interfere with anticonvulsant medication, and may lower seizure threshold.

Patients undergoing cancer treatment should consult their licensed medical practitioner for advice.

PRECAUTIONS: Vitamin B₉ alone is improper therapy in the treatment of pernicious anemia and other megaloblastic anemias where vitamin B₁₂ is deficient. Vitamin B₉ in doses above 0.1 mg daily may obscure pernicious anemia in that hematologic remission may occur while neurological manifestations progress.

PREGNANCY and NURSING MOTHERS: This product is not intended for use as a prenatal/postnatal multivitamin for lactating and non-lactating mothers. This product contains B vitamins plus NAC. Talk with your medical practitioner before using if pregnant or lactating.

HOW SUPPLIED: Levomefolate Calcium/Acetylcysteine/Mecobalamin/Algal Powder (6 mg-600 mg-2 mg-90.314 mg) is supplied as a coated, gray caplet debossed "V324", dispensed in bottles of 1000 caplets.

^†This product is a prescription-vitamin B₉ with or without other dietary ingredients that - due to increased vitamin B9 levels (AUG 2 1973 FR 20750), requires an R_x 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 similar product code, as required by pedigree reporting requirements and supply-chain control as well as - in some cases, for insurance-reimbursement applications.

Manufactured for:
Virtus Pharmaceuticals, LLC
Tampa, FL 33619

REV 5/2014

PRINCIPAL DISPLAY PANEL - 90 Tablet Bottle Label

VIRTUS
PHARMACEUTICALS

NDC^† 76439-329-11

Levomefolate Calcium*/
Acetylcysteine/Mecobalamin/
Algal Powder

Algal Powder
(6 mg-600 mg-2 mg-90.314 mg)

Prescription Vitamin B₉-Containing
Dietary Supplement

R_x

1000 Caplets       Made in the USA

Made in the USA