Serious Adverse Drug Events Reported to the FDA: Analysis of the FDA Adverse Event Reporting System 2006-2014 Database.

BACKGROUND: Data on adverse drug events (ADEs) observed at the population level provide important evidence regarding the safety of a pharmaceutical product in real-world settings. Recent patterns in serious and fatal ADE reporting have not been documented. OBJECTIVE: To assess recent patterns in serious and fatal ADE reports in the United States. METHODS: We conducted a retrospective analysis of the publicly available 2006-2014 FDA Adverse Event Reporting System database. Non-U.S. reports, reports from clinical trials, and reports with missing outcome data were excluded. The annual numbers of ADEs with reported outcome of death, disability, and other serious outcomes were determined. Types (direct, manufacturer expedited, or manufacturer periodic) and sources (consumer, health professional, or other) of these serious ADE reports were also identified. The distribution of serious ADE reports by patient age groups (< 18, 18-44, 45-64, and ≥ 65 years) was determined. Drugs listed as primary suspects in serious ADEs (death, disability, and other serious outcomes) were identified and ranked. Descriptive statistics were used to characterize the patterns in serious or fatal ADE reporting. RESULTS: From 2006 to 2014, the number of serious ADEs reported to the FDA increased 2-fold. A total of 902,323 serious outcomes were reported over the 9-year study period: 244,408 deaths, 72,141 disabilities, and 585,774 other serious outcomes. The relative percentage of reports of deaths was highest during 2012 (32.4%). The percentage of reports of disability was highest during 2006 (12.1%). Overall, the "other serious outcomes" category accounted for almost 65% of serious ADEs reports. Expedited reports from drug manufacturers were most common (about 72%) of the serious ADEs with available data on report type. Health professionals (47.3%) were the most common source of report followed by consumers (36.1%) and other sources (16.6%). A disproportionately high number of reported ADEs was among patients aged 45-64 years (40%) and ≥ 65 years (32.6%). Antineoplastic drugs were more frequently reported with deaths. Three antidepressant drugs were among the top 10 drugs reported with disability. During 2006-2014, there were 38 drugs with more than 1,000 reports of serious ADEs in a given year: 2 drugs currently withdrawn from the market (rofecoxib and parecoxib), 10 drugs with an FDA risk evaluation and mitigation strategies (REMS) program, 13 biologic or specialty drugs, and 14 others. CONCLUSIONS: An overall increase in the trend of the number of serious ADE reports was observed from 2006 to 2014. Drugs with a REMS program and biologic and specialty drugs were involved in a significant number of reported serious ADEs. Data on reporting patterns can guide surveillance and pharmacoepidemiological studies to understand the public health burden of serious ADEs. DISCLOSURES: No outside funding supported this study. Hansen has received consulting fees from and has provided expert testimony for Daichii Sankyo and Takeda. The other authors have nothing to disclose.

Guidelines on the use of finasteride in androgenetic alopecia.

BACKGROUND: Finasteride is a widely used drug in dermatology for the treatment of androgenetic alopecia. There are many reports of associated sexual side effects. This article reviews the use of once-daily 1 mg finasteride in androgenetic alopecia and its associated sexual adverse effects. METHODS: A literature search was performed to collect data on the use of finasteride in male pattern baldness. Relevant literature published till March 2014 was obtained from MEDLINE, EMBASE, CINAHL, Cochrane registers and LILACS. The keywords "finasteride", "male pattern baldness" and "androgenetic alopecia" were used for literature search. Similarly, a search was done for finasteride in female pattern hair loss with keywords "female pattern baldness", "finasteride" and "female pattern alopecia". All systematic reviews, meta-analyses, national guidelines, randomized controlled trials, prospective open label studies and retrospective case series in the English literature were reviewed. RESULTS: Two hundred sixty two studies were evaluated, twelve of which fulfilled the inclusion criteria. CONCLUSIONS AND RECOMMENDATIONS: Current evidence on the safety of finasteride indicates that it is safe but there is growing concern about its sexual side effects. In view of this, proper information should be provided to patients prior to starting treatment (Level of recommendation 1+, Grade of recommendation B). The reported sexual side effects are few and reverse with stoppage of the drug (Grade of recommendation B) but further studies are required.

New concerns about thalidomide.

Recently, the Food and Drug Administration (FDA) approved thalidomide for the treatment of the painful symptoms of erythema nodosum leprosum. This most recent FDA decision is a marked reversal to its previous rejection of this drug in the 1960s. The initial rejection by the FDA in the 1960s spared countless American children as thalidomide was shown to cause birth defects and miscarriages worldwide. The FDA's reputation as one of the finest consumer safety authorities was strengthened because of this decision. The recent approval of thalidomide by the FDA, with accompanying strict guidelines and monitoring procedures, has not only brought forth potential benefits, but also created new potential problems.

Thalidomide: the past, present, and future.

Treatment Review is intended to inform and update nurses about treatments relevant to HIV/AIDS. Product information presented in this column does not imply endorsement by the Association of Nurses in AIDS Care.

Thalidomide and the Titanic: reconstructing the technology tragedies of the twentieth century.

The Titanic has become a metaphor for the disastrous consequences of an unqualified belief in the safety and invincibility of new technology. Similarly, the thalidomide tragedy stands for all of the "monsters" that can be inadvertently or negligently created by modern medicine. Thalidomide, once banned, has returned to the center of controversy with the Food and Drug Administration's (FDA's) announcement that thalidomide will be placed on the market for the treatment of erythema nodosum leprosum, a severe dermatological complication of Hansen's disease. Although this indication is very restricted, thalidomide will be available for off-label uses once it is on the market. New laws regarding abortion and a new technology, ultrasound, make reasonable the approval of thalidomide for patients who suffer from serious conditions it can alleviate. In addition, the FDA and the manufacturer have proposed the most stringent postmarketing monitoring ever used for a prescription drug, including counseling, contraception, and ultrasonography in the event of pregnancy. The Titanic/thalidomide lesson for the FDA and public health is that rules and guidelines alone are not sufficient to guarantee safety. Continuous vigilance will be required to ensure that all reasonable postmarketing monitoring steps are actually taken to avoid predictable and preventable teratogenic disasters.

Thalidomide--the story goes on....

AIDS: The FDA has approved Thalidomide under the brand name THALOMID. The manufacturer, Celgene Corporation, has developed a distribution and training program for THALOMID, to minimize the possibility of the potentially devastating side effects associated with the drug. The program requires doctors and pharmacies to register with the FDA before they can dispense the drug. Clinical trials of Thalidomide will still continue, even though approval has been granted. Contact information is included for information on trials and expanded access programs.^ieng

Thalidomide approved.

AIDS: The FDA has approved the use of Thalidomide (Thalomid) for treating a leprosy-associated condition. However, Thalidomide can also be used for HIV-related conditions if a physician prescribes it for "off-label use". In HIV-positive people, Thalidomide has been shown effective in treating mouth, throat, vaginal, and rectal ulcers, and has also been successful in clearing severe diarrhea-causing microsporidiosis infections. The FDA has also granted permission to use Thalidomide for treating AIDS-related wasting and mycobacterial infections by giving Thalidomide an "orphan drug status". Severe restrictions have been established for use of Thalidomide by women, because of the drug's association with birth defects. Contact information is provided.^ieng

FDA approves fomivirsen, famciclovir, and Thalidomide. Food and Drug Administration.

AIDS: The FDA has recently approved three new drugs. Fomivirsen (Vitravene), developed by Isis Pharmaceuticals, was approved as a treatment for cytomegalovirus (CMV) retinitis. The drug prevents CMV replication by binding with the virus' genetic material. It is the first drug using antisense technology to win approval and is injected into the eye weekly or every other week. Famciclovir (Famvir) was approved for the treatment of HIV-related herpes simplex virus (HSV) infection. It is the first oral anti-HSV drug to be approved for use in people with HIV-related herpes. Thalidomide (Synovir), developed by Celgene, has received limited approval for the treatment of leprosy. It has also been used successfully in trials involving AIDS-related wasting and recurrent aphthous ulcers, although it has not been approved for these conditions.^ieng

Thalidomide's long and winding road.

AIDS: Thalidomide is a drug associated with devastating side effects. First prescribed in the late 1950s as a sedative, thalidomide caused more than 12,000 disfiguring birth defects, most commonly truncated arms and legs in infants, referred to as seal flipper limbs. Most alarming was that no link was made between the drug and birth defects in animal studies. The drug vanished from the market, except for use in treating leprosy. The history of the drug's use is outlined, along with its effects in treating progressive diseases such as HIV. The drug has never received marketing approval from the Food and Drug Administration (FDA), however, it was imported illegally by buyers' clubs in the United States. Results of several trials, including a Mexican study, showed the effectiveness of the drug. Side effects include sedation, rash, and neurotoxicity; some preliminary results suggest use of thalidomide can increase viral loads. Two expanded access programs exist today, and the manufacturer, Celgene, estimates that fewer than 10,000 patients will take the drug in its first year on the market due to safety concerns. Toratogenic drug concerns and preventing birth defects are critically important. The drug appears to be effective in non-pregnant patients and those suffering from diverse immune system and infectious disorders.^ieng