About

Orally administered, extended released, medical food* for use only under medical supervision for the dietary management of suboptimal folate levels in depressed patients.

Featuring Quatrefolic®, the (6S)-5-MTHF Glucosamine Salt Form of Folate

Why Is (6S)-5-MTHF Better Than Folic Acid and (6S)-5-MTHF Calcium Salt?

  • Not likely to mask B12 deficiency
  • Effectively lowers homocysteine[1]
  • Seven times more bioavailable than folic acid[2]
  • The active form of folate naturally present in the body
  • Preferred form, especially for those with disturbances in folate metabolism
  • Not affected by the MTHFR C677T polymorphism
  • Improved bioavailability over folic acid and (6S)-5-MTHF calcium salt
  • 100% more water soluble than (6S)-5-MTHF calcium salt

*Official FDA information about medical foods can be found in 21 U.S.C. sec. 360ee(b) (3), 21 C.F.R. sec. 101.9 (j) (8), and “Guidance for Industry: Frequently Asked Questions About Medical Foods” (May 2007), FDA website.


NutraIngredients Award Winner

XaQuil XR was awarded Strategic Product of the Year Medical Food Category at the 2016 NutraIngredients Awards

More Info

What is a Medical Food?

A medical food, is "a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation."

As defined in section 5(b)(3) of the Orphan Drug Act (21 U.S.C. 360ee(b)(3)).

The Research

There is clinical evidence that showed patients taking (6S)-5-MTHF calcium as adjunctive therapy with an antidepressant experienced superior outcomes compared to an antidepressant plus placebo.[1]

XaQuil XR consists of 30mg of Quatrefolic, (6S)-5-MTHF glucosamine salt in an extended released tablet. XaQuil XR’s form of folate has been shown to have improved bioavailability when compared to (6S)-5-MTHF calcium salt and folic acid.

XaQuil XR is also 100 times more water soluble than (6S)-5-MTHF calcium salt. This is shown in the graph and study notes below.

Quatrefolic Versus Folic Acid and (6S)-5-MTHF Calcium Salt

Preclinical Study

This test was a direct comparison between Quatrefolic, (6S)-5-MTHF calcium salt, and folic acid in rats. It showed the difference in bioavailability in vivo between the three folate generations

5-MTHF Plasma Levels in Rats After Oral Administration of Different Folates

Used with permission from Gnosis S.p.A.

Improved Bioavailability

(6S)-5-methyltetrahydrofolate hematic peak produced by an equivalent dose of the indicated folate source.

Used with permission from Gnosis S.p.A.

In a single-dose, balanced, two-sequence, two-period, two-treatment, randomized, crossover human study, Quatrefolic showed better bioavailability (+10%) than (6S)-5-MTHF calcium salt (Ca-L-5- MTHF).

Pharmacokinetic Study

Quatrefolic® Ca-L-5-MTHF
Pharmacokinetic parameter Mean SD CV% Mean SD CV% D%
Cmax (nmol/L) 94.55 21.98 23.2 85.29 28.46 33.4 10.9
AUC (nmol/L.h) 549.2 142.68 26.0 501.1 151.1 30.2 9.6
  1. Venn BJ, et al. Am J Clin Nutr. 2003 Mar;77(3):658-62. [PMID: 12600857]
  2. Willems FF, et al. Br J Pharmacol. 2004 Mar;141(5):825-30. [PMID: 14769778]

Used with permission from Gnosis S.p.A.

XaQuil XR

Label Details:

  •   Ingredients: Dicalcium phosphate, microcrystalline cellulose, coating (talc, shellac, vegetable glycerin, L-arginine, vegetable magnesium stearate, silica, sodium alginate, titanium dioxide, riboavin 5'-phosphate sodium), vegetable stearic acid, Quatrefolic® (6S)-5-methyltetrahydrofolic acid, glucosamine salt, vegetable magnesium stearate, and croscarmellose sodium.
  •   Usual Dosage: Take one tablet daily, or as directed by your physician. See package insert for complete information.
  •   Storage: Store at 20° to 25°C (68° to 77°F) {see USP controlled room temperature}.
  •   Warning: Keep this and all medications out of the reach of children. For use under the supervision of a physician.
XaQuil XR

XaQuil XR® Information

DESCRIPTION

XaQuil XR is a medical food for use under the supervision of a physician for the metabolic management of low 5-methyltetrahydrofolic acid (5-MTHF) levels associated with depression.

Medical foods are “intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation” (section 5(b)(3) of the Orphan Drug Act (21 U.S.C. 360ee(b)(3)). Such patients may have a limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or have other special medically-determined nutrient requirements that cannot be achieved by modification of the normal diet alone.1

INGREDIENTS
XaQuil XR Key ingredient:
Quatrefolic®
(6S)-5- methyltetrahydrofolic acid, glucosamine salt)
30 mg
C.A.S.# 1181972-37-1

Other Ingredients:
Dicalcium phosphate, microcrystalline cellulose, coating (talc, shellac, vegetable glycerin, L-arginine, vegetable magnesium stearate, silica, sodium alginate, titanium dioxide, riboflavin 5’-phosphate sodium), vegetable stearic acid, Quatrefolic® (6S)-5-methyltetrahydrofolic acid, glucosamine salt, vegetable magnesium stearate, and croscarmellose sodium.

XaQuil XR 30 mg tablets do not contain sugar, lactose, yeast, or gluten.

XaQuil XR is a medical food used under the supervision of a physician.

CLINICAL PHARMACOLOGY

XaQuil XR is a medical food, which consists of a proprietary biologically-active folate, 5-MTHF, glucosamine salt.

5-MTHF works to assist the body with regulating the synthesis or production of neurotransmitters found in the brain, such as serotonin, norepinephrine, and dopamine. Low levels of these neurotransmitters, which may be due to a genetic abnormality that reduces the body’s ability to convert folate into the active compound, 5-MTHF, have been associated with depression. It is estimated that this genetic abnormality is found in approximately 70 percent of people suffering from depression. The most common of which is called Methylenetetrahydrofolate Reductase (MTHFR) genetic polymorphism, which compromises a person’s ability to convert folic acid and dietary folate into 5-MTHF.

INDICATIONS AND USE
ADJUNCTIVE USE IN MAJOR DEPRESSIVE DISORDER
XaQuil XR is indicated for the distinct nutritional requirements of individuals who have suboptimal 5-methyltetrahydrofolic acid levels in the cerebrospinal fluid, plasma,

and/or red blood cells and have major depressive disorder (MDD), with particular emphasis as adjunctive support for individuals who are on an antidepressant.2-5

XaQuil XR is indicated regardless of MTHFR C677T polymorphism genotype.7

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

PRECAUTIONS
Folic acid, when administered in daily doses above 0.1 mg, 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-MTHF may be less likely than folic acid to mask vitamin B12 deficiency.8,9 Folate therapy alone is inadequate for the treatment of a B12 deficiency.

A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed, although not established in controlled trials, that treating such an episode with an antidepressant alone may increase the likelihood of a precipitation of a mixed/manic episode in patients at risk for bipolar disorder. XaQuil XR is not an antidepressant. However, 5-MTHF has been shown to enhance antidepressant effects of known antidepressants.3 Caution is recommended in patients with a history of bipolar illness. Patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder since mood elevation in this population is possible.

XaQuil XR should always be used under medical supervision.

PATIENT INFORMATION
XaQuil XR is a medical food, for use under the supervision of a physician and their direction.

INTERACTION WITH DRUGS
Before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all of 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 XaQuil XR.

XaQuil XR contains folate, which may have interactions with the following:

  • Antiepileptic drugs (AED): The AED class including, but not limited to, phenytoin, carbamazepine, primidone, valproic acid, 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 this AED in the blood and allowing breakthrough seizures to occur.10,11,13,16
  • Capecitabine: Folinic acid (5-formyltetrahydrofolate) may increase the toxicity of Capecitabine.12
  • 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.13
  • Fluoxetine: Fluoxetine exerts a noncompetitive inhibition of the 5-methyltetrahydrofolate active transport in the intestine.14
  • Isotretinoin: Reduced folate levels have occurred in some patients taking isotretinoin.15
  • Nonsteroidal Anti-inflammatory Drugs (NSAIDSs): NSAIDs have been shown to inhibit some folate dependent enzymes in laboratory experiments. NSAIDs include ibuprofen, naproxen, indomethacin, and sulindac.13
  • Oral Contraceptives: Serum folate levels may be depressed by oral contraceptive therapy.13
  • Methylprednisolone: Reduced serum folate levels have been noted after treatment with methylpredinisolone.13
  • Pancreatic Enzymes: Reduced folate levels have occurred in some patients taking pancreatic extracts.13
  • Pentamidine: Reduced folate levels have been seen with prolonged intravenous pentamidine.13
  • Metformin treatment in patients with type 2 diabetes decreases serum folate.17,18
  • Warfarin can produce significant impairment in folate status after a six-month therapy.19

ADVERSE REACTIONS
Allergic reactions have not been reported following the use of oral (6S)-5-methyltetrahydrofolic acid, glucosamine salt.

DOSAGE AND ADMINISTRTION
The usual adult dose is 30 mg given daily, with or without food, or as directed under medical supervision.

HOW SUPPLIED:

30 mg Bottle of 30 Product Code #53731-0003-03* Use under medical/ physician supervision
30 mg Packet of 1 Product Code #53731-0003-99* Professional samples. Not for sale.

XaQuil XR is a coated yellow, round, extended release tablet designed to be given once daily.

*PharmaceutiX™ does not represent these product codes to be National Drug Codes (NDC). Product codes are formatted according to standard industry practice, to meet the formatting requirements of pharmacy and health insurance computer systems.

STORAGE
XaQuil XR should be stored in a controlled room temperature environment. The product should be stored in a cool, dry place and protected from heat, light, and moisture.

REFERENCES

  1. United States Food and Drug Administration Title 21 Code of Federal Regulations. 101.9(j) (8).
  2. 1 Kelly CB et al. The MTHFR C677T Polymorphism is Associated with Depressive Episodes in Patients from Northern Ireland. J Psychopharmacol. 2004;18(4):567-71
  3. Godfrey PS, et al. The Lancet. 1990;336:392-5. [PMID: 1974941]
  4. Passeri M, et al. Aging Clin Exp Res. 1993;5(1):63-71.
  5. Guaraldi GP, et al. 1993;5(2):101-5. [PMID: 8348200]
  6. Di Palma C, et al. Is Curr Ther Res. 1994;55(5):559-68.
  7. Willems FF, et al. Br J Pharmacol. 2004;141(5):825-30. [PMID: 14769778]
  8. Akoglu B, et al. Euro J Clin Nutrition. 2007;1-6.
  9. Scott JM, Weir DG. The Lancet. 1981;2(8242):337-40. [PMID: 6115113]
  10. Hernandez-Diaz S. N Engl J Med. 2000;343(22):1608-14. [PMID: 11096168]
  11. Morrell MJ. Epilepsy Curr. 2002;2(2):31-34. [PMID: 15309159]
  12. Capecitabine Package Insert. Roche Laboratories. 2000.
  13. Natural Standard Research Collaboration (NIH). Folate (folic acid) Monograph 2009.
  14. Amiburu A, et al. J Physiol Biochem. 57(2), 71-80, 2001.
  15. Chanson A, et al. JEADV 2008, 22(1):94-100. [PMID: 18181979]
  16. Tatum W IV, et al. Arch Intern Med. 2004;164(2):137-45. [PMID: 14744836]
  17. Wulffelé MG, et al. J Intern Med. 2003; 254(5):455-63. [PMID: 14535967]
  18. Desouza C, et al. Drugs. 2002; 62(4):605-16. [PMID: 11893229]
  19. Sobczyriska-Malefora A, et al. Blood Coagul Fibrinolysis. 2009 June;20(4):297- 302. [PMID: 19349858]

Quatrefolic® is a registered trademark of Gnosis S.p.A. Produced under US Patent 7,947,662.

PATIENTS
Some or all of the following patents may apply:

US Patent No. 7,947,662

Other pending patent applications may also apply.

DISTRIBUTED BY:
PharmaceutiX
6900 Kingspointe Pkwy
Orlando, FL 32819
800-647-6100

Official FDA information about medical foods can be found in 21 U.S.C. sec. 360ee(b)(3), 21 C.F.R. sec. 101.9 (j)(8), and “Guidance for Industry: Frequently Asked Questions About Medical Foods” (May 2007), FDA website.


XaQuil XR® Tablets
XaQuil XR Capsules

REV. 122315

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