VP-HEME OB

Virtus Pharmaceuticals LLC

VP-HEME OB Tabs

FULL PRESCRIBING INFORMATION: CONTENTS*

• IRON, COBALAMINS & FOLATES
• MEDICAL FOODS & FOLATES
• MEDICAL FOODS
• REFERENCES
• Pedigree
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

FULL PRESCRIBING INFORMATION

90 Tablets
NDC: 76439-237-90
Rx
PENATAL / POSTNATAL
Prescription Folate

DESCRIPTION: VP-HEME OB Tabs 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-HEME OB Tabs should be administered under the supervision of a licensed medical practitioner.

Each oval, purple film-coated tablet contains the following dietary ingredients:

Other Ingredients: Microcrystalline Cellulose, Pregelatinized Starch, Di Calcium Phosphate, Purple Coating (hydroxypropylmethyl cellulose, titanium dioxide, polyvinyl alcohol, polyethylene glycol, talc, FD&C red #40 lake, FD&C blue #1 lake), Croscarmellose Sodium, Magnesium Stearate, Fumed Silica, Silicon Dioxide, Stearic Acid, Tripotassium Citrate, Citric Acid.

Since colors, flavors of natural origin vary from batch to batch in consistency - it may be necessary to substitute excipients as needed to ensure the highest therapeutic target, safety and quality.

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

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.

FOLATE REGULATION: 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 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 Rx on the label because of increased risk associated with masking of B₁₂ deficiency (pernicious anemia). As such, this product requires licensed medical supervision, an Rx status, and a National Drug Code (NDC) as required by pedigree reporting requirements and insurance-reimbursement applications.

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 anaemia.

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

Uses

INDICATIONS AND USAGE: VP-HEME OB Tabs is indicated for the distinct nutritional requirements of patients in need of PRENATAL/POSTNATAL dietary supplementation as determined by a licensed medical practitioner. VP-HEME OB Tabs is also indicated as supplementation therapy during pre/post pregnancy as well as while lactating /non-lactating.

VP-HEME OB Tabs should be administered under the supervision of a licensed medical practitioner.

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

WARNINGS: See product ingredients. Consult your licensed healthcare practitioner or pharmacist for more information.

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-HEME OB Tabs is a PRENATAL / POSTNATAL prescription folate to be used only under licensed medical supervision.

DRUG INTERACTIONS: Drugs which may interact with folate** 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. Ensure adequate medical supervision to ensure proper iron levels.
• 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.

**Folate is a broad term that includes folic acid and all reduced forms including l-methylfolate and folinic acid. VP-HEME OB Tabs does not contain l-methylfolate or folinic acid but these warnings are included as general folate information. Drugs which interact with vitamin B₁₂:

Drugs which interact with vitamin B₁₂:

• Antibiotics, cholestyramine, colchicines, colestipol, metformin, para-aminosalicylic acid, and potassium chloride may decrease the absorption of vitamin B₁₂.
• Nitrous oxide can produce a functional vitamin B₁₂ deficiency.

Drugs which interact with vitamin B₆:

• 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 D₃:

• 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.

Drugs which may interact with zinc:

• Concomitant administration of zinc supplements and certain antibiotics, specifically tetracyclines and quinolones, may decrease absorption of the antibiotic and potentially reduce its efficacy.

PREGNANCY and NURSING MOTHERS: VP-HEME OB Tabs is intended for use as a prescription PRENATAL folate before, during, and after pregnancy regardless of lactation status.

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. Mild transient diarrhea, polycythemia vera, itching, transitory exanthema and the feeling of swelling of the entire body have been associated with vitamin B₁₂.

DOSAGE AND ADMINISTRATION: One tablet 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.

HOW SUPPLIED: VP-HEME OB Tabs is supplied as oval, purple film-coated tablets debossed on one side with “VPHEME”, dispensed in bottles of 90 tablets. NDC: 76439-237-90

*This product is a PRENATAL/POSTNATAL prescription folate that contains folate in an amount higher than 0.1 mg, and has an increased risk associated with masking of vitamin B12 deficiency and must be administered under a physician’s supervision (AUG 3 1973 FR 20750). This product requires licensed medical supervision and a Rx status as required by pedigree reporting requirements.

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.

Rx

Manufactured for:
Virtus Pharmaceuticals LLC,
Tampa, Florida 33619

VIRTUS
PHARMACEUTICALS

MADE IN CANADA

Rev. 9/2013

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

VIRTUS
Pharmaceuticals

NDC 76439-237-90

VP-HEME-OB
Tabs

PRENATAL / POSTNATAL

Prescription Folate

R_x

90 Tablets