Chapter Updates

Content Update for Chapter 10, "Prevention of Pregnancy and Sexually Transmitted Infections"

FDA Label Warnings for Nonoxynol-9

The following information supplements and updates text in Chapter 10, "Prevention of Pregnancy and Sexually Transmitted Infections," in the Handbook of Nonprescription Drugs, 15th Edition.

Nonoxynol-9

The U.S. Food and Drug Administration has issued a final rule that establishes new warning statements and other labeling information for all over-the-counter (OTC) vaginal contraceptive drug products that contain nonoxynol-9. By June 19, 2008, labels for these products must include the warnings that nonoxynol-9 does not provide protection against infection from HIV or other sexually transmitted infections (STIs) and that this agent in stand-alone vaginal contraceptives and spermicides (foams, films, gels, inserts) can irritate the vagina and rectum, possibly increasing the risk of contracting HIV/AIDS from an infected partner.1

Revised Labeling Requirements
Specific warnings that must appear on the immediate container label, or outside container or wrapper of the retail package, are as follows:1 The following additional labeling information may appear under the “Other information” section, either on the outside container or wrapper, or in a package insert:1
The following labeling information must appear on the outside container or wrapper labeling under the heading “Other information”:1
Supporting Clinical Evidence
This ruling is the culmination of FDA’s review of available relevant data and public responses to the proposed rule published in 2003.2

Dissenters from FDA’s proposed ruling asserted during the public comment period that the agency relied primarily on the studies by Van Damme et al.3 and Kreiss et al.4 to support the position that use of nonoxynol-9 is linked to increased risk of HIV infection. The respondents challenged the validity of the findings in both studies.1,p.71772 The respondents also contended that two other studies, Roddy et al.5 and Richardson et al.6, support a conclusion opposite to that of the studies by Van Damme et al. and Kreiss et al., or weaken the conclusion that use of N9 spermicide products may increase the risk of HIV infection from an infected partner.1,p.71774

FDA responded that, even with the noted limitations of the VanDamme et al. study, the agency believes the study findings provide evidence that “N9 may increase the risk of HIV-1 infection in a population already at increased risk for HIV-1 infection.”1,p.71774 With regard to the Kreiss et al. study, the agency noted that “…early termination of the study for safety reasons (i.e., that the seroconversion results had become inconsistent with the hypothesis of clinically beneficial effects of N9 in preventing HIV seroconversion) was ethically appropriate, and suggests an outcome consistent with the results of the Van Damme et al. study.1,p.71774

Readers who wish to review these four studies as well as more current studies are referred to the References and Additional Reading sections below.

References
  1. Over-the-counter vaginal contraceptive and spermicide drug products containing nonoxynol 9; required labeling; final ruling. Federal Register. December 19, 2007;72(243):71769-85. (Codified at 21 CFR Part 201.) Also available at: http://www.fda.gov/OHRMS/DOCKETS/98fr/07-6111.pdf.
  2. Over-the-counter vaginal contraceptive drug products containing nonoxynol 9; required labeling; proposed ruling. Federal Register. January 16, 2003;68: 2254–62. Also available at: http://a257.g.akamaitech.net/7/257/2422/14mar20010800/
    edocket.access.gpo.gov/2003/pdf/03-902.pdf.
  3. Van Damme L, Niruthisard S, Atisook R, et al. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomized controlled trial. Lancet. 2002;360:971-7.
  4. Kreiss J, Ngugi E, Holmes K, et al. Efficacy of nonoxynol-9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes. JAMA. 1992;268:477-82.
  5. Roddy RE, Zekeng L, Ryan K, et al. A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases. N Engl J Med. 1998;339:504-10.
  6. Richardson BA, Lavreys L, Martin HL Jr, et al. Evaluation of a low-dose nonoxynol 9 gel for the prevention of sexually transmitted diseases, a randomized trial. Sex Transm Dis. 2001;28:394-400.
Additional Reading