Download Summary analysis of the safety of nonoxynol

Summary analysis of the safety of nonoxynol
Nonoxynol (nonoxynol-9 or nonoxinol) is a nonprescription vaginal spermicide, which
may also possess some antimicrobial/antiviral properties. Nonoxynol is used as a condom
additive and is present in a variety of products for vaginal administration, including
foams, gels, films, sponges and suppositories. Within the recommendations for use of the
various products, the vagina can be exposed to an extremely variable range of amounts of
nonoxynol and this may have substantial toxicological implications. The findings of a
given study may not be relevant for other ways of using the drug.
Vaginal and also penile discomfort, irritation, soreness, itching, dysuria, local
inflammation and genital ulcerations (mainly of the vulva) occur in about 5-10% of users
(1). Allergic reactions can occur in either partner but are rare. When used regularly,
nonoxynol may suppress the growth of Lactobacillus acidophilus and lead to urogenital
colonisation by pathogens, notably Escherichia coli. Nonoxynol sponges have been
connected with the toxic shock syndrome. The most worrisome warning in the literature
is that injury to the epithelial lining of the vagina may increase HIV transmission. A large
meta-analysis has recently shown that there is a slightly increased relative risk of HIV
infection when nonoxynol is used by sex workers (2,3). (However, other more aggressive
agents that are sometimes used, for instance metacresol-sulphonic acid-derived products,
may be more dangerous.)
The WHO Uppsala Monitoring Centre’s database (UMC)
The case reports of suspected adverse reactions stored in the WHO database generally
concern the use of nonoxynol containing vaginal products, with or without condoms.
There are a total of 227 case reports regarding altogether 309 suspected adverse reactions
stored in association with this drug. One third of the reports concern unintended
pregnancy (103, mainly from Denmark and the United States). 96 reports concern local
reactions, e.g. application site reactions (13), vaginitis (30), vaginal haemorrhage (2),
vulva disorder (3), allergic reaction (3), oedema and oedema genital (6), pain (22),
dermatitis contact (5), dyspareunia (2), pruritus and pruritus genital (7), cervix lesion (3)
or, in the partner, balanoposthitis and penis disorder (3). In addition, there is a cluster of
reports regarding the urinary tract or bladder: dysuria (17), cystitis and cystitis
haemorrhagic (8), micturition abnormal (3), haematuria (3), urethral disorder (2) and
urinary retention (3). In a number of cases, e.g. vaginitis, dysuria or cystitis, an infection
is likely to have happened, and an additional series of reports of infectious episodes is
shown in table 1. Also, there are a number of reports of abortion or other foetal disorders
(14, table 2).
Table 1. Infectious events reported in
suspected association with nonoxynol
Infection
4
Salpingitis
3
Urinary tract infection
3
Moniliasis genital
1
Table 2. Foetal disorders reported in
suspected association with nonoxynol
Abortion
4
Sex chromosome disorder
6
Ectromelia
1
Heart malformation
1
Pulmonary malformation
1
Transposition of the great vessels
1
Discussion
The pattern of adverse events reported in association with nonoxynol is roughly in
accordance with the information in the literature. The predominance of unintended
pregnancy is in keeping with the fact that nonoxynol is not an effective contraceptive. In
this perspective the reports of foetal disorders could be explained as coincidence. On the
other hand, some studies appear to have suggested an increased risk of congenital
malformations and spontaneous abortions with the use of vaginal spermicides around the
time of conception (1). The small cluster of 6 case reports of ‘sex chromosome disorder’,
all from the same country, remains unexplained.
The number of reports of infection is only small, but illustrates that such complications
may extend beyond the vagina. Since sexual intercourse is a risk factor for infections of
the female urogenital tract, however, reports of infection may partly represent
confounding by indication for use. In the literature also a few case reports have been
described of urinary retention, presumably as a result of nonoxynol entering the urethra.
Nonoxynol is one of the few available spermicide drugs and has been used world-wide in
vast quantities. In this perspective the number of reports to the UMC is smaller than
might have been expected. Presumably there has been much underreporting, also because
these products may often not have been acquired in a pharmacy and not been regarded as
reportable medicine. The existence of underreporting is also suggested by the finding that
the vast majority of reports came from only three countries (USA, UK and Denmark).
Conclusions
The case reports stored in the WHO database are generally in accordance with the
information in the literature and are no reason to assume that the vaginal use of nonoxinol
is connected with unexpected frequent or serious toxicity.
A toxicological evaluation is difficult, because nonoxynol is used in highly variable
concentrations, formulations and intensity, and under very different circumstances.
Nonoxynol is not a powerful spermicide, but when used occasionally it can be a sensible
and safe contraceptive adjuvant, i.e. when used in combination with condoms or a
diaphragm. Discomfort and, rarely, allergic reactions can occur in either partner. When
used intensively the vaginal epithelium can be injured. In addition to local inflammation,
epithelial injury may increase susceptibility to systemic infections, in particular with the
HI virus. Nonoxynol does not protect against AIDS or other sexually transmitted diseases
but may, in the contrary, be associated with a (small) increased risk for acquiring HIV
infection.
1. Drugdex Drug Evaluation, Micromedex, 2002
2. Wilkinson D, Tholandi M, Ramjee G, Rutherford GW. Nonoxynol-9 spermicide for
preventioin of vaginally acquired HIV and other sexually transmitted infections:
systematic review and meta-analysis of randomised controlled trials including more
than 5000 women. Lancet 2002;360:613-7.
3. Wilkinson D. Nonoxynol-9 fails to prevent STDs, but microbicide research continues.
Lancet 2002;360: 962.
Medical Advisor Ronald Meyboom at the Uppsala Monitoring Centre Uppsala Sweden,
Uppsala 9 December 2002