VP CH Plus

Virtus Pharmaceuticals LLC

VP-CH Plus

FULL PRESCRIBING INFORMATION: CONTENTS*

• IRON, COBALAMINS & FOLATES
• MEDICAL FOODS & FOLATES
• MEDICAL FOODS
• REFERENCES
• Pedigree
• WARNINGS:
• Drugs which interact with vitamin B:
• Drugs which may interact with vitamin D:
• KEEP THIS OUT OF REACH OF CHILDREN.
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

FULL PRESCRIBING INFORMATION

Softgels

NDC*: 76439-242-30

R_x

PRENATAL/POSTNATAL
Prescription Folate

DESCRIPTION: VP-CH Plus is an orally administered PRENATAL/POSTNATAL prescription folate specifically formulated for the dietary management of patients with unique nutritional needs requiring increased folate levels.

VP-CH Plus should be administered under the supervision of a licensed medical practitioner.

Each oblong, purple softgel contains the following dietary ingredients:

Calcium (citrate)	104 mg
Iron (carbonyl)	29 mg
Vitamin D3 (cholecalciferol)	400 IU
Vitamin E (dl-alpha tocopherol acetate)	30 IU
Vitamin B6 (pyridoxine HCl)	25 mg
Folic Acid	1 mg
Docusate Sodium	50 mg
Docosahexaenoic acid (40% DHA from 650 mg omega-3 oil blend)	265 mgcontains less than 1% EPA from approximately 40% DHA derived from at least 650 mg of ultra-purified fish and/or algal oil.

Daily Values not established for patients with unique nutritional needs who are in need of supplementation as directed by a licensed medical practitioner.

Other Ingredients: Carmine, Ethyl Vanillin, FD&C Blue #1, FD&C Red #40, Gelatin, Glycerin, Natural Creamy Orange Flavor, Purified Water, Soybean Oil, Soy Lecithin, Titanium Dioxide, Yellow Beeswax.

This product contains soy, fish (tuna) and/or algal. This product also contains carmine and bovine gelatin.

This product has been manufactured in a facility that also manufactures products containing tree nuts, peanuts, fish, egg, wheat, milk, soy and shellfish. Individuals with allergic tendencies to these substances should use discretion.

The term "folate" refers to B vitamins that include folic acid and any forms of active pteroylglutamates regardless of the reduction state of the molecule. Folates are best known for their indication in pregnancy. During the first four weeks of pregnancy (when women do not even realized that they have conceived), adequate maternal folate intake is essential to reduce the risk of NTDs, which are congenital malformations produced by a failure of the neural tube to form and close properly during embryonic development. However, folic acid, including reduced forms such as folinic acid, may obscure pernicious anemia above 0.1 mg doses, and must be administered under the supervision of a licensed medical practitioner. The 1971 and 1973 Federal Registers - in addition to the 1980 Folic Acid OTC Monograph, addressed this concern while establishing that increased folate was proper therapy in megaloblastic anemias of tropical and nontropical sprue, nutritional origin, pregnancy, infancy and childhood-specifically where homocysteine levels were elevated or risk of neural tube defects was at issue. (2,3) Special attention is paid to the condition of pernicious anemia due to the relationship between folate and cobalamin, and possible risks associated with metabolic imbalances that can exasperate that condition. Due to concerns surrounding pernicious anemia, 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 [emphasis added]. 4

*It is not known with certainty whether or not l-methylfolate can obscure pernicious anemia above 0.1 mg doses, so caution is advised also with this form of folate.

IRON, COBALAMINS & FOLATES

The megaloblastic state results from an imbalance between supply cofactors necessary for DNA synthesis / production. In the presence of B₁₂ and/or folate deficiency-but specifically folate deficiency, megaloblastic change results. Inversely, increased demand for DNA in physiologically hyperproliferative states, such as hemolytic anemia or cancer, can lead to megaloblastic change in the face of freely available folate and B₁₂.

MEDICAL FOODS & FOLATES

Folic acid - including reduced forms, may be added to medical foods as defined in section 5(b)(3) of the Orphan Drug ACT (21USC 360ee(b)(3)), or to food (21 CFR 172.345). 5

MEDICAL FOODS

Medical foods are intended for a patient who has a limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or who has other special medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone. 6

REFERENCES

• The Federal Register Notice of April 9, 1971 (36 FR 6843).
• The Federal Register Notice of August 2, 1973 (38 FR 20750).
• The Federal Register Notice of October 17, 1980 (45FR 69043 at 69044).
• The Federal Register Notice of August 2, 1973 (38 FR 20750).
• Code of Federal Regulations Title 21 Section 172.345.
• Code of Federal Regulations Title 21 Section 101.9(j)(8).

Pedigree

This product is a prescription-folate with or without dietary ingredients - that due to increased folate 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). As such, this product requires licensed medical supervision, an R_x status, and a National Drug Code (NDC) as required by pedigree reporting requirements and insurance-reimbursement applications.

Uses

INDICATIONS AND USAGE: VP-CH Plus is indicated for the distinct nutritional requirements of patients in need of PRENATAL/POSTNATAL dietary supplementation as determined by a licensed medical practitioner.

VP-CH Plus should be administered under the supervision of a licensed medical practitioner.

^{FOLATE MECHANISM OF ACTION: FOLATE 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 folate-deficiency anemia.}

^{FOLATE PHARMACOLOGY: FOLATES are metabolized to the active substrate tetrahydrofolate (THF) which is also the active moiety of all folates.}

CONTRAINDICATIONS: This product is contraindicated in patients with a known hypersensitivity to any of the ingredients, including fish or fish oil.

WARNINGS:

PRECAUTIONS: General: Folate, when administered as a single agent in doses about 0.1 mg daily, may obscure the detection of vitamin B₁₂ deficiency (specifically, the administration of folic acid may reverse the hematological manifestations of B₁₂ deficiency, including pernicious anemia, while not addressing the neurological manifestations). Folate therapy alone is inadequate for treatment of a vitamin B₁₂ deficiency.

PATIENT INFORMATION: VP-CH Plus is a PRENATAL/POSTNATAL prescription folate to be used only under licensed medical supervision.

DRUG INTERACTIONS: Drugs which may interact with folateFolate is a broad term that includes folic acid and all reduced forms including l-methylfolate and folinic acid. include:

• Antiepileptic drugs (AED): The AED class including, but not limited to, phenytoin, carbamazepine, primidone, valproic acid, fosphenytoin, valproate, phenobarbital and lamotrigine have been shown to impair folate absorption and increase the metabolism of circulating folate.
• Additionally, concurrent use of folic acid has been associated with enhanced phenytoin metabolism, lowering the level of the AED in the blood and allowing breakthrough seizures to occur. Caution should be used when prescribing this product among patients who are receiving treatment with phenytoin and other anticonvulsants.
• Capecitabine: Folinic acid (5-formyltetrahydrofolate) may increase the toxicity of capecitabine.
• Cholestyramine: Reduces folic acid absorption and reduces serum folate levels.
• Colestipol: Reduces folic acid absorption and reduces serum folate levels.
• Cycloserine: Reduces folic acid absorption and reduces serum folate levels.
• Dihydrofolate Reductase Inhibitors (DHFRI): DHFRIs block the conversion of folic acid to its active forms, and lower plasma and red blood cell folate levels. DHFRIs include aminopterin, methotrexate, pyrimethamine, triamterene, and trimethoprim.
• Fluoxetine: Fluoxetine exerts a noncompetitive inhibition of the 5-methyltetrahydrofolate active transport in the intestine.
• Isotretinoin: Reduced folate levels have occurred in some patients taking isotretinoin.
• L-dopa, triamterene, colchicine, and trimethoprim may decrease plasma folate levels.
• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): NSAIDs have been shown to inhibit some folate dependent enzymes in laboratory experiments.
• NSAIDs include ibuprofen, naproxen, indomethacin and sulindac.
• Oral Contraceptives: Serum folate levels may be depressed by oral contraceptive therapy.
• Methylprednisolone: Reduced serum folate levels have been noted after treatment with methylprednisolone.
• Pancreatic Enzymes: Reduced folate levels have occurred in some patients taking pancreatic extracts, such as pancreatin and pancrelipase.
• Pentamidine: Reduced folate levels have been seen with prolonged intravenous pentamidine.
• Pyrimethamine: High levels of folic acid may result in decreased serum levels of pyrimethamine.
• Smoking and Alcohol: Reduced serum folate levels have been noted.
• Sulfasalazine: Inhibits the absorption and metabolism of folic acid.
• Metformin treatment in patients with type 2 diabetes decreases serum folate.
• Warfarin can produce significant impairment in folate status after a 6-month therapy.
• Heme-iron: Can compete for transport and reduce folate absorption.
• Folinic acid may enhance the toxicity of fluorouracil.
• Concurrent administration of chloramphenicol and folinic acid in folate-deficient patients may result in antagonism of the haematopoietic response to folate.
• Caution should be exercised with the concomitant use of folinic acid and trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection as it is associated with increased rates of treatment failure and mortality in a placebo controlled study.

Drugs which interact with vitamin B:

• Vitamin B₆ should not be given to patients receiving the drug levodopa because the action of levodopa is antagonized by vitamin B₆. However, vitamin B₆ may be used concurrently in patients receiving a preparation containing both carbidopa and levodopa.
• Isoniazid can produce a vitamin B₆ deficiency.

Drugs which may interact with vitamin D:

• Certain thiazide diuretics, such as hydrochlorothiazide, as well as antacids, bile acid sequestrants (such as cholestyramine), mineral oil, orlistat, olestra, cimetidine, and anticonvulsant medications may reduce the absorption or increase the catabolism of vitamin D.
• Vitamin D supplementation should not be given with calcium in those with hypercalcemia or conditions that may lead to hypercalcemia such as hyperparathyroidism and those who form calcium-containing kidney stones.

PREGNANCY and NURSING MOTHERS: VP-CH Plus is intended for use before, during and after pregnancy for lactating and non-lactating mothers. Talk with your medical practitioner to ensure adequate prenatal/postnatal supplementation.

ADVERSE REACTIONS: Allergic sensitization has been reported following both oral and parental administration of folic acid, and may possibly occur with other forms of folate. Paresthesia, somnolence, nausea and headaches have been reported with vitamin B₆.

DOSAGE AND ADMINISTRATION: Before, during, and after pregnancy, one softgel capsule, taken by mouth daily, or as directed by a licensed medical practitioner.

STORAGE: 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 can discolor or erode the capsule.

HOW SUPPLIED: VP-CH Plus is supplied as oblong, light purple soft gelatin capsules imprinted with "V224", dispensed in bottles of 30 softgel capsules.

NDC This product is a prescription folate supplement with other dietary ingredients that - due to increased folate 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). As such, this product requires licensed medical supervision, an R_x status, and a National Drug Code (NDC) as required by pedigree reporting requirements and insurance-reimbursement applications. : 76439-242-30

KEEP THIS OUT OF REACH OF CHILDREN.

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

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

R_x

Manufactured for:
Virtus Pharmaceuticals, LLC
Tampa, Florida 33619

MADE IN CANADA

VIRTUS
PHARMACEUTICALS

Rev. 9/2013

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Virtus
PHARMACEUTICALS

NDC: 76439-242-30

VP-CH Plus
PRENATAL / POSTNATAL

Prescription Folate

R_x

30 Softgels