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.