1 INTRODUCTION
Harmful medicines are still available in developing countries. Some
drugs banned in their country of origin are marketed in developing
countries by a few pharmaceutical companies. Due to a lack of
legislation and weak legal regulation of drugs in developing countries,
these drugs are dispensed to patients without consideration of their
potential hazards.
Some international corporations that have established their roots in
evolving countries have a goal of attaining the maximum level of income
irrespective of humanitarian foresight. However, pharmaceutical and many
other companies also use developing countries’ markets for selling goods
they cannot dispose of elsewhere, such as contaminated food and
radioactive waste [1].
There are two drugs available in Aden community pharmacies
(phenolphthalein (PP) and ketoconazole (KZ)) that are globally banned.
PP was the essential constituent in several over-the-counter laxatives
for most of the 20th century. The U.S. Food and Drug
Administration FDA categorized PP as “safe and effective” in 1975
[2]. However, in 1997, the FDA anticipated that PP should be
reclassified as “not commonly documented as safe and effective”
[3] after a 2-year feeding study in rodents showed elevated
frequencies of neoplasms of the ovary, adrenal gland, kidney, and
hematopoietic system [4]. Consequently, the United States
voluntarily withdrew most PP, including that contained in laxatives,
from the market. Studies indicated the genotoxicity of PP [4] and
its ability to cause oxidative damage [5] and bind to estrogen
receptors [6]. The individual data on laxative usage and human
cancers specified that its use is not associated with an increased risk
of large-bowel cancer [7–13].
The United States Food and Drug Administration (FDA) issued a Drug
Safety Communication restricted the use of Nizoral (KZ) oral tablets on
July 26, 2013 [14]. However, KZ was the only existing systemic
remedy for a wide variety of fungal infections. The FDA’s warning
emphasized the potential of a possibly fatal drug-induced liver injury
(DILI) related to KZ usage, in addition to other risks. The declaration
stated that “Nizoral oral tablets should not be a first-line treatment
for any fungal infection, [and] Nizoral should be used only when
alternative antifungal therapies are not available or tolerated.” At
the same time, the European Medicines Agency’s Committee on Medicinal
Products for Human Use (EMA-CHMP) [15] has suggested that the
selling authorization for oral KZ as an antifungal be postponed.
The CHMP stated that the hepatoxic risk associated with the usage of KZ
overshadows its benefits. Physicians should select an alternative
medicine to treat patients with fungal infections. The patients being
treated with KZ should consult their physicians. Oral KZ for Cushing’s
syndrome and topical dosage forms containing KZ are not included in this
warning. The FDA Communication[14] states the following: “Serious
hepatic injury was identified as the major toxicity for Nizoral tablets
and was noted to be unrelated to dose, duration, or indication for
treatment. In showing the benefit-risk evaluation, normal side effect
shows the DILI, including mortalities and hepatic transplantations,
feedback from the FDA Adverse Event Reporting System (AERS) were judged
independently by a hepatology expert in FDA. The total hazard for
KZ-induced serious liver injury seemed higher than that accompanying
other azole antifungal drugs as indicated from pharmacoepidemiologic
studies.”
As part of a larger medication safety study among community pharmacists
in Yemen, this study was performed to assess the availability of two
banned medicines in Yemen i.e. PP and KZ.