Laxatives/Drug Interaction, Ingredient Combination Revisited In Comments

The drug interaction warning being planned for OTC laxatives should recommend consulting a health care professional before taking the products with prescription medications, not all drugs, Procter & Gamble states in recent comments to FDA.

FDA has developed a label warning for inclusion in the final monograph on laxatives that reads: "Ask a doctor or pharmacist before use if you are taking any other drug. Take this product two or more hours before or after other drugs. Laxatives may affect how other drugs work."

The language was developed in response to a 1996 citizen petition from P&G proposing a precautionary statement focused on the Rx drug risk.

As an alternative, P&G urges that the statement refer consumers to a doctor or pharmacist "if you are taking a prescription drug" but retain the recommendation, "take this product two or more hours before or after other drugs."

"Although it is possible that OTC drugs have a potential to interact with laxative medications, P&G's proposed precautionary statements selectively addresses prescription medicines" for a number of reasons, the company explains.

Specifying Rx drugs would "focus consumers'... attention on those medications used in treating medically significant illnesses or conditions, where avoidance of drug interactions would be most critical," according to P&G.

The company also pointed out there is precedence in the market for specifying Rx drugs in a drug-drug interaction warning, citing its own Metamucil products and Phillips' Milk of Magnesia , marketed by Bayer.

Published literature supporting a precautionary statement primarily includes cases involving Rx drugs, the comments point out. In addition, "the vast majority of cases from P&G's spontaneous adverse event data base suggested drug interaction involved prescription drugs."

On a separate issue, P&G reiterates an earlier recommendation that FDA reconsider the method it used in setting minimum "divided" doses for bulk-forming laxatives such as methylcellulose and polycarbophil. Recommendations regarding a series of smaller doses of such ingredients are being developed to offer an alternative to a single large dose.

The company proposes that the method used to determine the minimum divided doses for psyllium products be applied to other bulk-forming actives.

The comments were among several individual submissions filed in response to FDA's October decision to reopen and update the administrative record for OTC laxatives. The tentative final monograph on laxatives was published in 1985.

In other filings, Dulcolax marketer Boehringer Ingelheim urged the agency to reconsider approving the active ingredient combination of bisacodyl and docusate sodium.

In 1995, FDA denied a request from Ciba Consumer Pharmaceuticals (now Novartis) to approve the combination (¹ (Also see "Phillips Milk of Magnesia data "inadequate" to support stool softener indication -- FDA." - Pink Sheet, 21 Aug, 1995.), p. 19). Dulcolax was previously marketed by Ciba.

FDA has concluded that bisacodyl is a safe and effective laxative ingredient based on "exhaustive" studies evaluating its carcinogenic potential, BI notes. In addition, the firm says it is "not aware of any pharmacokinetic interactions between bisacodyl and DSS that would detract from the safety or efficacy of either ingredient."

Approval of a product combining bisacodyl and DSS would establish a "viable alternative" in the laxative category, BI points out, suggesting American consumers may already view bisacodyl as a "preferred, stimulant laxative product."

The comments cite market statistics indicating bisacodyl products are at least as popular as senna laxatives on a worldwide basis and may be growing faster than senna in the U.S.

Global sales for bisacodyl-containing OTC laxatives were over $170 mil. in the fiscal year ending September 2003, while sales of senna-based laxatives were more than $174 mil., according to the firm.

In the U.S., retail sales of senna products declined by nearly 10% in 2003 and bisacodyl laxatives are selling at a ratio of approximately 1:1 compared with senna products, BI maintains.