FDA MedWatch Research Articles

Atorvastatin-Induced Fixed Drug Eruption Clopidogrel-Induced Acute Hepatitis Bilateral Angle-Closure Glaucoma Induced by Chlorthalidone Risk of Anaphylactic Reactions with Intravenous Iron Products Zonisamide-Induced DRESS with Eosinophilic Pneumonia.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

Adverse Events Associated With Sodium Phosphate (Saline) Enema in Adults: A 46-Year Database and Clinical Survey

Introduction: Sodium phosphate enemas are marketed in the U.S. for treatment of occasional constipation and as a bowel preparation. In January 2014, the FDA issued a Safety Communication warning that use of more than one sodium phosphate enema [SPE] in a 24-hour period could cause rare but serious cardiac and renal effects. This study sought to evaluate U.S. adverse event reporting for SPE among adults and to assess U.S. gastroenterologists' [USGI] knowledge regarding the dosing of SPE. Methods: All U.S. adverse event [AE] reports associated with SPE use in adults > 12 yrs were reviewed during the period from June 1968 through December 2014. Sources included an enema manufacturer's safety database, medical literature, and FDA MedWatch reports. Events associated with oral sodium phosphate were excluded. Serious AEs [SAE] and non-serious AEs [NSAE] were defined by the FDA Code of Federal Regulations. Overdose was defined as use of more than the labeled amount of SPE/24 hrs. A survey evaluating USGI knowledge regarding SPE dosing was conducted in January 2015 using a nationally diverse sample. Results: AEs were reported in 608 subjects (Table 1), including 56 SAE and 552 NSAE. The most frequent SAE was electrolyte disturbance and/or acute kidney injury, occurring in 20/56 cases. Fatality was recorded in 12 cases, including electrolyte disturbance (7) and arrhythmia (3). Overdose was more frequent in SAE compared to NSAE (p < 0.00001). Among fatal SAE, overdose was reported in 8/12 cases (75%) vs. 8/44 non-fatal cases (18.2%; p < 0.001). Only 24% of USGI knew that the maximum recommended SPE dose is one bottle/24 hrs (Table 2). In 15/16 SAE cases identified as overdose, a health care provider improperly dosed the enema.Table 1: Adverse Events Associated with Sodium Phosphate (Saline) Enema (1968-2014)Table 2: Survey of U.S. Gastroenterologists on Sodium Phosphate (Saline) Enema (n=50)Conclusion: Overdose of sodium phosphate enema was significantly associated with both serious adverse events and fatality when compared to non-serious adverse events. A majority of U.S. gastroenterologists are unaware of appropriate enema dosing guidelines. Efforts to educate consumers and clinicians on the proper use of sodium phosphate (saline) enema should be undertaken to reduce the risk of adverse events.

Trimethoprim-Sulfamethoxazole-Induced Rhabdomyolysis; Gabapentin-Induced Hypoglycemia in Diabetic and Nondiabetic Patients; Purple Glove Syndrome After Oral Phenytoin Administration; Acute Dystonic Reaction After Methylphenidate Initiation; Serotonin Syndrome with Vilazodone Monotherapy; Cabozantinib-Associated Dermatologic Adverse Reactions.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

Earlier identification of risks: cumulative probability analysis of time to safety alerts for therapeutic monoclonal antibodies.

Previous analysis of US FDA Medwatch safety alerts for monoclonal antibody therapeutics demonstrated that premarketing clinical trials can predict more than half of safety concerns. We expanded this analysis to assess whether the predictable alerts are detected sooner than the unpredictable alerts. Times to alert were compared using Mann-Whitney test, Kolmogorov-Smirnov test, and using curves displaying cumulative frequencies of alerts over time. Until December 31, 2013 inclusive, 76 Medwatch alerts for therapeutic monoclonal antibodies were reported: 43 predictable vs. 33 unpredictable. Predictable alerts were reported at a median (IQR) of 41 (19-77) months after approval vs. 53 (23-73) months for the unpredictable alerts. The mean (SE) was 52.07 (6.69) months and 55.91 (7.06) months for the predictable and unpredictable, respectively. Although the difference of 12 months between medians of time to alert was observed, the difference was not demonstrated as significant. Cumulative frequency curves show that predictable alerts were detected sooner until month 73 after approval, when ~ 80% of alerts were detected. Immunological reactions (such as infusion reactions, anaphylaxis, and reactions due to antibodies) were identified early; all 12 such alerts were released before the curves of cumulative frequencies cross at month 73. On the other hand, reactions occurring after the curves cross are predominantly late-occurring cancers and opportunistic infections. The results imply that focus on predictable reactions defined as potential risks may play a role in early detection of important safety concerns.

Patient with terbinafine-induced subacute cutaneous lupus erythematosus followed by thalidomide-induced orofacial neuropathy; Beta blocker use, hypertension, and the risk of psoriasis; eczematous reaction to intravenous immunoglobulin; nicolau syndrome after intra-articular glucocorticoid injection; troponin leak associated with drug-induced methemoglobinemia.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

Patient with Terbinafine-Induced Subacute Cutaneous Lupus Erythematosus Followed by Thalidomide-Induced Orofacial Neuropathy; Beta Blocker Use, Hypertension, and the Risk of Psoriasis; Eczematous Reaction to Intravenous Immunoglobulin; Nicolau Syndrome After Intra-Articular Glucocorticoid Injection; Troponin Leak Associated with Drug-Induced Methemoglobinemia

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

Pancreatitis-associated with riluzole; linezolid-induced hypoglycemia; sorafenib-induced acute generalized exanthematous pustulosis; creatine supplementation-induced thrombotic events; acute pancreatitis associated with quetiapine; hypomagnesemia and seizure associated with rabeprazole.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

Pancreatitis-associated with riluzole; linezolid-induced hypoglycemia; sorafenib-induced acute generalized exanthematous pustulosis; creatine supplementation-induced thrombotic events; acute pancreatitis associated with quetiapine; hypomagnesemia and seizure associated with rabeprazole.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

Cardiac conduction disturbance after loperamide abuse

Context. Prescription opioid abuse is a major public health concern and an ongoing epidemic in the United States. Loperamide is a widely available and inexpensive over-the-counter antidiarrheal with peripheral mu-opioid receptor activity. Online resources discuss the use of loperamide for the amelioration of withdrawal symptoms or recreational abuse. We describe the clinical course of 5 patients abusing loperamide, 3 of whom had life-threatening cardiac arrhythmias. Methods. In this observational case series, patients with cardiac arrhythmias or history of loperamide abuse with cardiac arrhythmias were identified; 5 patients were identified and 4 of the 5 patients were seen directly at the bedside. Clinical profile and outcome of patients is reported. Results. We report 5 patients with history of loperamide abuse; 3 of the 5 patients had life-threatening cardiac arrhythmias. One of the patients experienced a second life-threatening arrhythmia after he resumed loperamide abuse. Loperamide levels were obtained in 4 of the 5 patients and were at least one order of magnitude greater than therapeutic concentrations. Discontinuation of loperamide resulted in complete resolution of cardiac conduction disturbances. Conclusion. This case series describes several patients with cardiac conduction abnormalities and life-threatening ventricular arrhythmias temporally related to loperamide abuse. With the recent efforts to restrict the diversion of prescription opioids, increasing abuse of loperamide as an opioid substitute may be seen. Toxicologists should be aware of these risks and we urge all clinicians to report such cases to FDA Medwatch®.

Recurrent small intestinal ileus due to valsartan; compulsive behaviors related to rasagiline use; lacosamide-induced acute pancreatitis; brief psychotic disorder after abrupt withdrawal of hydroxyzine; hydroxyurea-associated acral erythema; penicillamine-induced degenerative dermatosis.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

Methimazole-induced chronic arthritis; bilateral gynecomastia associated with the combination of methylphenidate and paroxetine; adrenal suppression and cushingoid features with inhaled fluticasone; pulmonary thromboembolism due to paliperidone.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) Med Watch program (800-FDA-1088). If you have reported an interesting, preventable ADR to Med Watch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's Med Watch program and Temple University School of Pharmacy. ISMP is an FDA Med Watch partner.

Metformin-induced hepatitis; paliperidone-related peripheral edema; vasospastic angina induced by oral capecitabine; skin hyperpigmentation due to long-term voriconazole therapy; vaccine-associated measles.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

Vigabatrin-Induced Encephalopathy; Fidaxomicin Hypersensitivity Reactions; Vemurafenib-Induced DRESS; Severe Alkalosis and Hypokalemia With Stanozolol Misuse; Isotretinoin-Associated Lip Abscess; Eltrombopag-Associated Hyperpigmentation.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MEDWATCH program (800-FDA-1088). If you have reported an interesting, preventable ADR to MEDWATCH, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MEDWATCH program and Temple University School of Pharmacy. ISMP is an FDA MEDWATCH partner.

Furosemide-Induced Immune Thrombocytopenia; Type I Interferon-Induced Ischemic Colitis; Dronedarone-Associated Acute Renal Failure; Modafinil-Induced Psychosis

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

ISMP Adverse Drug Reactions - Tranexamic Acid-Induced Toxic Epidermal Necrolysis; Hypoglycemia Caused by Tramadol; Neutropenia Associated with Prolonged Daptomycin Use; Thrombotic Thrombocytopenic Purpura Associated with Intravenous Opana ER; Bell's Palsy Due to Vemurafenib

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

ISMP Adverse Drug Reactions.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

ISMP Adverse Drug Reactions.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

The faces of pharmacy: Students and pharmacists stepping forward

The faces of pharmacy: Students and pharmacists stepping forward

Bevacizumab and central nervous system (CNS) hemorrhage

Bevacizumab is widely used and may cause life-threatening bleeding. We attempted to identify clinical characteristics associated with central nervous system (CNS) hemorrhage in a broad population. We performed a retrospective review of the FDA MedWatch database of adverse events reported with bevacizumab from 11/1997 to 5/2009. Our search used keywords: bleeding, hemorrhage, cerebral, intracranial, subarachnoid, cerebellar, hemorrhagic stroke and brain. A total of 17,466 reports were included in the database: 154 described CNS hemorrhage in 99 patients, and 1,041 reports described non-CNS bleeds. Median age was 62 years, and the primary cancers were consistent with indications for bevacizumab. Patients received a median of three (1-36) doses of bevacizumab prior to the bleed. Thirty percent had documented history of hypertension. Sixteen patients with CNS hemorrhage were reported to have CNS metastases. Death was reported as a complication of hemorrhage in 48 %. The most common predisposing factor for CNS bleeds was use of medications associated with bleeding, followed by thrombocytopenia. In this database, 154 of 1,195 reports of bleeding associated with bevacizumab described a CNS bleed. Although CNS bleeds were not common, they were the reported cause of death in two-thirds of cases.

Educating patients about FDA’s MedWatch

Many patients may be unaware of FDA's MedWatch Adverse Reporting Program and the role they can play in helping the agency identify potential safety issues with products in the marketplace. Educating patients about the program, the importance of reporting, and how to submit a report to FDA will aid in safeguarding future patients from potentially serious adverse events.