DMPS Is Not an FDA-Approved Drug,
but the FDA Is Permitting Its Sale

Stephen Barrett, M.D.

Dimercapto-propane sulfonate (DMPS) is one of several drugs that can bind metals when administered by mouth or injection. It is not FDA-approved but has been available from compounding pharmacies for many years. Its main use in the United States is to treat alleged heavy metal toxicity. Many practitioners who administer DMPS falsely claim that the mercury content of amalgam fillings causes mercury toxicity. Others falsely claim that it is effective for treating autism. To help persuade the patients—or in the case of children, their parents—these practitioners typically perform a "provoked" urine test in which a dose of DMPS or another chelator is administered before the urine specimen is collected. By attaching to lead, mercury, and/or other heavy metal ions, chelators cause them to be secreted more rapidly than usual, which artificially and temporarily raises the urine level(s). The patient is then advised that that test report indicates toxicity and that chelation therapy is needed [1]. Some doctors treat autistic children with a skin preparation of DMPS, even though it has been demonstrated that applying DMPS to the skin does not result in absorption [2].

The FDA has jurisdiction over the manufacturing and labeling of DMPS that is marketed in interstate commerce. The activities of practitioners are regulated by state licensing boards. At least eleven practitioners who used DMPS for diagnosis or treatment have been disciplined for unprofessional conduct by their state medical board [3-13]. At present, the main importer and distributor of DMPS in the United States is McGuff Compounding Pharmacy Services, of Santa Ana, California, which is made by an FDA-registered subsidiary of Heyl Chem.-pharm. Fabrik GmbH &Co. KG of Berlin, Germany (commonly referred to as Heyl).

FDA regulation of compounding pharmacies has been inconsistent. Federal law states that it is not legal to compound drugs that are not approved in the U.S., unless they are subject to an approved investigational new drug application (IND). DMPS is not FDA-approved, and there is no reason to believe that an IND exists. In 2008, an attorney who was concerned about DMPS's legality received this email:

From: CDER DRUG INFO
Subject: RE: Drugs@FDA Comments
To: Christopher Grell, Esq.
Date: Thursday, August 7, 2008, 11:58 AM

Thank you for your message to the Center for Drug Evaluation and Research (CDER), one of the five centers within the Food and Drug Administration (FDA).

DMPS is not an approved drug in the U.S. You can not compound drugs that are not approved in the U.S., unless they are subject to an approved investigational new drug application (IND). IND's are confidential. Compounding pharmacies can not mass produce their drugs as they then would be considered a drug manufacturer. See our compounding web page at . . . and view our compliance policy guide on pharmacy compounding.

Sincerely,

Division of Drug Information
D202D

This communication is consistent with 21 CFR 10.85 (k) and constitutes an informal communication that represents our best judgment at this time but does not constitute an advisory opinion, does not necessarily represent the formal position of FDA, and does not bind or otherwise obligate or commit the agency to the views expressed.

The above e-mail was said to be "informal," but the FDA's policy was expressed in a 2007 case in which the agency seized 17 vials of DMPS along with samples of several other drugs from ApotheCure, Inc., in Dallas, Texas [14]. Despite this, however, the FDA is permitting McGuff to sell it.

It is legal to compound any bulk drug substance that the FDA includes in a final list of drugs that can be compounded. FDA regulations at 21 CFR 207.3(a)(4) defines bulk drug substance as "any substance that is represented for use in a drug and that, when used in the manufacturing, processing, or packaging of a drug, becomes an active ingredient or finished dosage form of the drug, but the term does not include intermediates used in the synthesis of such substances." No final list has been issued, but the FDA is considering substances that have been nominated for use in compounding under section 503A of the Federal Food, Drug, and Cosmetic Act. McGuff, the American Association of Naturopathic Physicians (AANP), the Alliance for Natural Health, the Integrative Medical Consortium, and the International Association of Compounding Pharmacists have nominated DMPS for the final list of bulk substances that can be used in compounding [15].

In June 2016, the FDA Pharmacy Compounding Advisory Committee spent half a day discussing whether DMPS should be the final list. Kathy Robie Suh, MD, PhD, an FDA clinical team leader, stated that her team opposed inclusion because investigation of DMPS had not been been proven safe or beneficial as currently used [16]. Paul Anderson, N.D., who represented the AANP, testified that in 2003, DMPS proved to be life-saving in treating people who had been poisoned with arsenic at a church function. He also estimated that since 1999, one American compounder had processed 10,000 orders for an estimated total of 67,000 doses of DMPS and had received no complaints, and that he himself had administered 5,000 doses to treat people exposed to arsenical pesticides. Toxicologist Jeffrey Brent, M.D., Ph.D., testified that the database of the Toxicology Investigators Consortion, to which nearly all practicing toxicologists in the Unites States use, indicates that since 2010, "not a single medical toxicologist has found a reason to use DMPS in this country, the reason being that we would reserve it for really high quality acute arsenic or mercury poisoning, which . . . is very rare." Possible ways to reduce inappropriate use were discussed, but a compounding pharmacist who was a non-voting member of the Advisory Committee warned that if the FDA found a way to curb such use, DMPS would no longer be sufficiently profitable to manufacturer [17].

In the end, the committee voted 8-3 to place DMPS on the final list. Several members who voted favorably expressed discomfort but decided that the rare need for emergency use for arsenic poisoning outweighed the risks people of getting DMPS inappropriately. I do not agree. It seems to me that there should be a way to make DMPS available for emergency use without leaving thousands of people per year at the mercy of practitioners who misdiagnose toxicity.

In September 2016, the FDA announced that "to avoid unnecessary disruption to patient treatment" while the FDA considers the nominated substances, it would not act against a nominated product provided that it is manufactured by an establishment registered with the FDA, fulfills certain other conditions, and does not appear to present significant safety risks [18,19].

The FDA's final determination will not be made until (a) input from the advisory committee process has been considered, (b) all reviews have been finalized, (c) consultation with the United States Pharmacopeia has occurred, and (4) public comment has been considered through notice and comment rulemaking. If the FDA ultimately decides to tolerate the marketing of DMPS, the least it can do is issue a public warning and ask state licensing boards to attack its inappropriate use.

References

  1. Barrett S. How the urine toxic metals test is used to defraud consumers. Quackwatch, March 27, 2011.
  2. Cohen JP and others. Plasma and urine dimercaptopropanesulfonate concentrations after dermal application of transdermal DMPS (TD-DMPS). Journal of Medical Toxicology, Nov 10, 2012.
  3. Consent agreement and order. In the matter of Robert W. Snider, M.D. New York State Office of Professional Medical Conduct. #BPMC 99-4, Jan 2, 1999.
  4. Stipulated settlement and disciplinary order. In the matter of the first amended accusation against Ilona Abraham, M.D. Medical Board of California Case No. 05-1999-102590, April 13, 2004.
  5. Consent order. In re: Robban Sica, M.D. Connecticut Department of Health Petition No. 2002-0306-001-043. Feb 15, 2005.
  6. Consent order. In re: Warren Levin, M.D. Connecticut Department of Health Petition No. 2003-01 14-001-005, Aug 16, 2005.
  7. Consent order. In re: George Zabrecky, D.C. Connecticut Board of Chiropractic Examiners Petition No. 2003-1019-007-001, Nov 16, 2006.
  8. Consent order. In re: Rashid A. Buttar, D.O. Medical Board of North Carolina, March 26, 2010.
  9. Order for summary suspension of license to practice medicine. In the matter of Mark R. Geier, M.D. Before the Maryland State Board of Physicians. Case Numbers: 2007-0083, 2008-0454 & 2009-0308, April 27, 2011.
  10. Stipulated order. In the matter of Christopher Hatlestad, M.D. Before the Oregon Medical Board, Jan 10, 2013.
  11. First amended accusation. In the matter of the first amended accusation against: Ronald Wempen, M.D. Medical Board of California Case No. 09-2011-217227 OAH, April 10, 2013.
  12. Consent order. In the matter of Richard E. Layton, M.D. Before the Maryland State Board of Physicians. Case Number: 2012-0820, Oct 17, 2013.
  13. Stipulated order. In the matter of Richard Heitsch, M.D. Before the Oregon Medical Board, Aug 6, 2015.
  14. Application for inspection warrant under the Federal Food, Drug, and Cosmetic Act. In the manner of establishment inspection of ApotheCure, Inc. United States District Court for the Northern District of Texas, Dallas Division, Case 3:07-mj-00346, filed August 3, 2007.
  15. FDA Briefing Document: Pharmacy Compounding Advisory Committee (PCAC) Meeting, June 23, 2016.
  16. Suh KR. Slide presentation. FDA Pharmacy Compounding Advisory Committee meeting, afternoon session, June 23, 2016
  17. Transcript. FDA Pharmacy Compounding Advisory Committee meeting, afternoon session, June 23, 2016, pp 139-200.
  18. FDA issues final guidances on interim policy for certain bulk drug substances used in compounding. FDA Web site, Sept 13, 2016.
  19. FDA Center for Drug Evaluation and Research. Interim policy on compounding using bulk drug substances under Section 503A of the Federal Food, Drug, and Cosmetic Act: Guidance for industry, June 2016.

This article was revised on September 30, 2016

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