Prior to the
development of isotretinoin, the main stay treatment of moderate to severe or
persistent acne was oral antibiotics such as the tetracyclines and
erythromycin. While these drugs have proven efficacy, they worked against only
one contributing factor of acne – the Propionibacteriumacnes bacteria. The
antibiotics gradually became less effective over time as more resistant strains
of the bacterium became prominent.
An early, effective
treatment of acne was high doses of the fat-soluble vitamin A. At these dose
levels (sometimes 500,000 IU per day) effects such as reduced production of
sebum and dry hair could be noticed. However the vitamin also had many other
prominent side effects which inhibitedits widespread use.
The development of the
retinoic acid derivative isotretinoin(13-cis-retinoic acid), and its release in
1982 by Hoffmann-La Roche,was a great step forward in the treatment of acne.
The synthetic compoundprovided better therapeutic benefit than vitamin A, while
also producing feweradverse effects. In February 2002, Roche's patents for
isotretinoin expired and there are now many other companies selling cheaper
generic versions of the drug.
Because of a 1984 study
funded by Roche, high dosages of the drug became main stream in treatment.
Lower dosages were found to be effectivein treatment by independent research
(see dosage section of this article), but Roche's dosage recommendations still
continue to be used.
From the time of its
introduction the drug was known to have teratogenic potential, and pregnancies
with the drug were strongly discouraged. When they occurred, they were found to
have approximately 30% rates of congenital malformation, versus a 3-5% baseline
risk. Beginning in 1998, prescriptions of the drug came under scrutiny, as
fewer than half of prescribers were testing for pregnancy, usually relying on
less sensitive urine tests. On the grounds that pregnancies by women taking the
drug had been underreported by the manufacturer between 1982 and 2000, and that
once generic manufacturers entered the market risk management was no longer
centralized, theFDA instituted restrictions on prescribing and dispensing the
drug, first withthe "System to Manage Accutane Related
Teratogenicity" (SMART) in 2000,and subsequently the iPLEDGE program in
2006. A retrospective cohort studyrecently found that pregnancy rates were
quite high during the period (1 per 30women per year), but 84% of pregnancies
were ended by induced abortion.
In countries that do
not restrict distribution ofisotretinoin, pharmacists recommend 5mg or 10mg
daily, since at lower dosagesthe adverse side effects are diminished.
Isotretinoin in topical form is alsoprescribed.
Isotretinoin is
available over the internet from countrieswhere it can be dispensed without a
prescription. It is an ongoing problem forgovernments where a prescription is
required, as it is mailed illegally acrossborders.
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