Labeling change: New warning proposed for nonoxynol-9 contraceptive drugs
Spermicide labeling to spell out ineffectiveness against HIV, STDs
Since research appeared in 2000 regarding the ineffectiveness of the spermicide nonoxynol-9 (N-9) against HIV,1 you have counseled patients not to rely on the spermicide as a means of HIV prevention. You reinforced that message again in 2002, when further research indicated that N-9 failed to protect against such sexually transmitted diseases (STDs) as urogenital gonorrhea and chlamydia.2
Now the Food and Drug Administration (FDA) is proposing a labeling change for over-the-counter vaginal contraceptives containing N-9. The new labeling, when approved, will help users understand that the use of such products can increase vaginal irritation, which actually may heighten the possibility of acquiring the AIDS virus and other STDs from infected partners.
The FDA has published its proposed labeling in the Federal Register,3 and is requesting public comment on the changes. The deadline is April 16 for submitting comments on the proposed labeling statements. (See the "Resources" section at the end of this article for information on how to submit comments.)
Review label changes
The FDA is proposing to require the following warnings be added to the labeling of all marketed OTC vaginal contraceptives containing N-9: 3
- "For vaginal use only."
- "Sexually transmitted diseases (STDs) alert: This product does not protect against the AIDS virus (HIV) or other sexually transmitted diseases (STDs).’’
- "Ask a doctor before use if you have a new sex partner, multiple sex partners, or unprotected sex. Frequent use (more than once a day) of this product can increase vaginal irritation, which may increase the risk of becoming infected with the AIDS virus (HIV) or other STDs from infected partners. Ask a doctor or other health professional for your best birth control method."
- "Stop use and ask a doctor if you or your partner get burning, itching, a rash, or other irritation of the vagina or penis.’’
The agency also is proposing the following information, which could be included in the package insert:
- "Studies have raised safety concerns that frequent use (more than once a day) of products containing nonoxynol-9 can increase vaginal irritation, which may increase the risk of getting the AIDS virus (HIV) or other STDs from infected partners. Vaginal irritation may include symptoms such as burning, itching, or a rash, or you may not notice any symptoms at all. If you use these products frequently and/or have a new sex partner, multiple sex partners, or unprotected sex, see a doctor or other health professional for your best birth control and methods to prevent STDs."
- "Correct use of a latex condom with every sexual act will help reduce the risk of getting the AIDS virus (HIV) and other STDs."
Reports spur changes
Reports issued in 2002 by the Atlanta-based Centers for Disease Control and Prevention (CDC) and the Geneva-based World Health Organization (WHO) helped spur the proposed labeling changes. The CDC’s May 2002 report recommended that women, particularly those at risk for HIV or STDs, be counseled that N-9 contraceptives do not protect against such infections.4
WHO issued revised public health guidelines in June 2002 on the use of N-9 for HIV and STD prevention, as well as for pregnancy prevention in populations at high risk for HIV.5 The guidelines stated that "spermicides containing nonoxynol-9 do not protect against HIV infection and may even increase the risk of HIV infection in women using these products frequently.’’ The guidelines also advised women at high risk of HIV infection against using N-9 spermicides for contraception.
Since the issuance of the two reports, many manufacturers have moved to delete N-9 products from their lines. Such manufacturers include New York City-based Planned Parenthood Federation of America, which has discontinued production of Planned Parenthood condoms lubricated with N-9; New Brunswick, NJ-based Johnson & Johnson, which has ceased production of its KY Plus lubricant with N-9 as well as an N-9 lubricated condom marketed in South America; and Mayer Laboratories of Oakland, CA, which has halted the use of N-9 in its Aqua Lube Plus lubricant, as well as use of the spermicide in any of its condom lubricants.6
Rectal use questioned
Impetus to remove N-9 from products has come from a broad-based coalition of more than 85 scientists and health groups that has issued a call to manufacturers to make such a move in light of concerns over use of these products in anal sex. (See "Resources section at the end of this article for contact information to join the call against such products.) The coalition is not seeking the removal of N-9 contraceptive products designed exclusively for vaginal use because they represent a contraceptive option for women who are at low risk of HIV infection or other STDs.
Use of N-9 condoms and lubricants has been widespread among gay men seeking protection against HIV and other STDs. A 1998 study reported that more than three-fourths of gay men surveyed used lubricants more than 80% of the time; among them, 41% actively sought N-9 products.7 Despite public health warnings about N-9’s inability to prevent such disease transmission, a 2001 survey of gay men in San Francisco indicated many continued to use N-9 products for protection.8
"It is of great importance that N-9 should not be used as a lubricant for anal sex, because I believe that the data suggest that the increase in transmission risk is even higher,"9 states Allan Rosenfield, MD, dean of the Mailman School of Public Health at the New York City-based Columbia University.
While the FDA’s proposed labeling change is a positive step, further language should be added to strengthen the warning message, says Lori Heise, director of the Global Campaign for Microbicides, an international coalition of groups based in the Washington, DC, office of PATH (Program for Appropriate Technology in Health).
"I think there is a missed opportunity in the proposed language to make clear that these products are harmful if used rectally," she says. "And while they do have language in there that says for vaginal use only,’ I think that is a very weak way to communicate [the warning]." Another message that must be conveyed is that microbicide options are in the research pipeline and must be pursued, says Heise. The failure of N-9 as a microbicide does not take away from the promise of other potential products, she maintains. "It is really important, given that the spermicidal products with N-9 do not look to be protective, that we adequately fund and pursue research into microbicides," states Heise.
1. Van Damme L, Ramjee G, Alary M, et al. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: A randomised controlled trial. Lancet 2002; 360:971-977.
2. Roddy RE, Zekeng L, Ryan KA, et al. Effect of nonoxynol-9 gel on urogenital gonorrhea and chlamydial infection. JAMA 2002; 287:1,117-1,122.
3. 68 Fed Reg 2254 (Jan. 16, 2003).
4. Centers for Disease Control and Prevention. Nonoxynol-9 spermicide contraception use — United States 1999. MMWR 2002; 51:389-392.
5. World Health Organization. WHO/CONRAD Technical Consultation on N-9. Summary Report. Geneva; Oct. 9-10, 2001. Accessed at www.conrad.org.
6. Zimmerman R. Some makers, vendors drop N-9 spermicide on HIV risk. Wall Street Journal Sept. 25, 2002: Accessed at www.aegis.com/news/wsj/2002/WJ020905.html.
7. Gross M, Buchbinder SP, Celum C, et al. Rectal microbicides for U.S. gay men. Are clinical trials needed? Are they feasible? HIVNET Vaccine Preparedness Study Protocol Team. Sex Transm Dis 1998; 25:296-302.
8. Mansergh G, Marks G, Rader M, et al. Reducing nonoxynol-9 use among men who have sex with men in order to decrease risk for HIV infection. Presented at the 14th International Conference on HIV/AIDS. Barcelona, Spain; July 2002. Abstract MoPeD3547.
9. Phillips DM, Taylor CL, Zacharopoulos VR, et al. Nonoxynol-9 causes rapid exfoliation of sheets of rectal epithelium. Contraception 2000; 62:149-154.
• To submit written comments to the Food and Drug Administration on the proposed labeling changes, contact: Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville MD 20852. Submit electronic comments to www.fda.gov/dockets/ecomments. Three copies of all written comments are to be submitted; one copy is sufficient for electronic submission. Comments are to be identified with the docket number 80N-0280.
• To get more information on the "Call to Discontinue Nonoxynol-9 for Rectal Use," contact: Global Campaign for Microbicides c/o PATH, 1800 K St. N.W., Suite 800, Washington, DC 20006. Telephone: (202) 822-0033. Fax: (202) 457-1466. E-mail: firstname.lastname@example.org. Web: www.global-campaign.org; click on "N-9 Call and Resources."