DESCRIPTION

XIZFLUS is an orally-administered nutritional product dispensed by prescription for the clinical dietary management of suboptimal hydrogen sulfide levels related to metabolic imbalances in endogenous hydrogen sulfide biochemistry. Use under medical supervision.

INGREDIENTS
Each XIZFLUS serving contains:
     Sodium polysulthionate‡     400 mg
    5-methyltetrahydrofolate     500 mcg

 ‡ Proprietary matrix of alpha sulfur, sodium sulfate, sodium thiosulfate obtained by reacting sodium hydrosulfide with sodium metabisulfite in an acidic medium

INDICATION

XIZFLUS is indicated for the distinct nutritional requirements of certain individuals with suboptimal endogenous hydrogen sulfide levels that cannot be corrected through diet alone, with a particular emphasis in persons who have inborn errors of cystathionine beta-synthase (CBS), cystathione gamma-lyase (CSE), and/or 3-mercaptopyruvatesulfurtransferase (3-MST). Clinical dietary management in patients who, as a result of a condition or disease, have limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients associated with endogenous hydrogen sulfide biochemistry. Use under medical supervision.1-6

In patients with suboptimal hydrogen sulfide levels, and as determined by your licensed medical practitioner, XIZFLUS may be administered as rescue or adjunctive nutritional therapy to address the risk of suboptimal hydrogen sulfide which can lead to oxidative stress, inflammatory, and/or vascular complications.1-4 The adjunctive use of XIZFLUS enables medical practitioners to combine therapeutic modalities (dietary management and drug therapy).1

CONTRAINDICATIONS

XIZFLUS is contraindicated in patients with known hypersensitivity to any of the components contained in this product.

WARNINGS AND PRECAUTIONS

GENERAL
Sulfur, by itself, is not toxic to our bodies. However, some people are allergic to relatives of sulfur such as sulfites and sulfa drugs. Certain sulfites can trigger asthma and other allergic reactions in people who are sensitive. Sulfa drugs can cause hypoglycemia (low blood sugar), skin rashes, high fever, headache, fatigue, and gastric problems for people with alpha drug allergies. Tell your health care provider if you think you may be allergic to sulfur-containing substances.

Folic acid, when administered in daily doses above 0.1mg, may obscure the detection of 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). 5-methyltetrahydrofolate may be less likely than folic acid to mask vitamin B12 deficiency.9-10 Folate therapy alone is inadequate for the treatment of a B12 deficiency.

Interaction with Drugs:
Before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. No decrease in effectiveness of drugs has been reported with the use of XIZFLUS.

Hydrogen sulfide may induce cytochrome P450 2B67 and 2E18, therefore it may decrease the half-life of medications metabolized by these enzymes. Careful monitoring of concomitant medications metabolized by these enzymes is recommended.

ADVERSE REACTIONS
Mild gastrointestinal (GI) issues such as flatulence and nausea were observed in sodium polysulthionate patients.1 All GI incidences were categorized as “mild” and no patients discontinued due to adverse events1. Allergic reactions have not been reported following the use of oral sodium polysulthionate.

USE IN SPECIFIC POPULATIONS
Pregnancy: XIZFLUS has not been studied in pregnant women. The choice to administer XIZFLUS during pregnancy is at the clinical discretion of the prescribing physician.

Labor and Delivery/NursingMothers: XIZFLUS has not been studied in labor and delivery. The choice to administer XIZFLUS during labor and delivery is at the clinical discretion of the prescribing physician.

Pediatric Use: XIZFLUS has not been studied in a pediatric population. The choice to administer XIZFLUS in pediatric populations is at the clinical discretion of the prescribing physician.

Geriatric Use: Clinical studies with XIZFLUS have not included sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger subjects.

OVERDOSAGE: No specific information is available on the treatment of overdosage with XIZFLUS.

XIZFLUS has been self-affirmed as Generally Recognized as Safe (GRAS). The highest level of sodium polysulthionate consumption has been 1,600MG per day in clinical studies although anecdotal reports of 3,000mg per day have used without adverse events..

DOSAGE

The adult dose of XIZFLUS is 1-2 servings twice a day, or 400–800mg sodium polysulthionate and 0.5-1mg 5-methyltetrahydrofolate twice per day (BID). For people who are sensitive to medications, a starting dose of 1 serving twice daily is recommended for the first week prior to titrating to a higher dose of 800mg twice daily if warranted. One to two (1-2) servings can be administered twice daily with or without food or as directed under medical supervision.

CLINICAL PHARMACOLOGY

Sodium polysulthionate: consists of a biologically active sulfur based nutrients in a proprietary matrix of alpha sulfur, sodium sulfate, and sodium thiosulfate derived from food sources. In a study of health controls and heart failure patients, oral sodium polysulthionate increased hydrogens sulfide and nitric oxide levels (p<0.05).1

Folate: folate is essential for the production of certain coenzymes in many metabolic systems such as purine and pyrimidine synthesis. Through one-carbon metabolism 5-methyltetrahydrofolate plays an essential role in homocysteine metabolism. Homocysteine metabolizes in the body to produce hydrogen sulfied, which is a strong antioxidant and vasorelaxation factor. At an elevated level, homocysteine inactivates proteins by homocysteinylation including its endogenous metabolizing enzyme, cystathionine gamma-lyase. Thus, there is a reduced production of endogenous hydrogen sulfide during hyperhomocysteinemia.12 5-methyltetrahydrofolate along with methylcobolamin is an essential co-factor in the conversion of homocysteine to methionine.13

INSTRUCTIONS FOR USE

• Pour serving size of 0.014 ounces into cup or glass
• Add at least 4 oz of water (or other liquid as preferred)
• Stir until fully mixed
• Drink all of the contents immediately
• Alternatively, product can be mixed with foods such as pudding or yogurt
• A recommended dose is 1 to 2 servings twice daily or as directed by the healthcare provider.

PATIENT INFORMATION:
XIZFLUS is a dietary management / prescription (Rx)† nutritional product to be used only under licensed medical supervision and direction. Your licensed medical practitioner may choose to prescribe XIZFLUS along with other medications.

HOW SUPPLIED

XIZFLUS is a is a dietary management / prescription (Rx)† nutritional product

XIZFLUS Canister 100 grams Product Code # 69597-921-01* Use under medical/physician supervision.
Each canister contains 250 servings. A 30 day supply is typically 60-120 servings

XIZFLUS containers contain light-yellow colored powder consisting of 100 g of sodium polysulthionate and 5-methyltetrahydrofolate. XIZFLUS does not contain any milk products such as lactose, casein, or whey. XIZFLUS is gluten-free, dye-free, and soy-free. XIZFLUS is manufactured in accordance with current Good Manufacturing Practice (cGMP).

XIZFLUS may- under certain circumstances, be dispensed through a certified mail-order program so long as there is a record of prescription AND confirmation that the patient is under licensed medical supervision. This product is not Orange Book (OB) rated product, therefore all prescriptions using this product shall be pursuant to State statues as applicable.

† This product is a prescription-folate with or without other dietary ingredients that – due to increased folate levels increased risk associated with masking of B12 deficiency (pernicious anemia) requires administration under the care of a licensed medical practitioner (61 FR 8760).14-16 The most appropriate way to ensure pedigree reporting consistent with these regulatory guidelines and safety monitoring is to dispense this product only by prescription (Rx). The ingredients, indication or claims of this product are not to be construed to be drug claims.

STORAGE AND HANDLING

Store at controlled room temperature 15oC to 30oC (59oF to 86oF). Protect from heat, light and moisture.

PACKAGE LABEL