MedWatch Program Research Articles

Erythematous Rash Following Romiplostim Administration in a Patient with Autoimmune Lymphoproliferative Syndrome

To report a case of erythematous rash induced by romiplostim administration in a patient with autoimmune lymphoproliferative syndrome (ALPS). A 19-year-old female with ALPS-related thrombocytopenia (platelet count 4 × 10(3)/μL) successfully treated with romiplostim 500 μg weekly for 9 months presented with a grade 3 maculopapular rash. Symptoms on presentation included purpuric, erythematous pustules confined to the trunk following romiplostim administration the previous day. A punch biopsy of skin from the patient's right lower abdomen revealed perivascular chronic inflammation with numerous eosinophils consistent with drug reaction. The patient had received romiplostim 500 μg weekly with no other reports of rash until this time. Romiplostim was discontinued, the patient was monitored, and the rash resolved within 1 week. Romiplostim was then restarted at 200 μg weekly. The patient has achieved platelet normalization at a current romiplostim dose of 250 μg weekly with no further adverse reactions. ALPS is a rare autoimmune disorder with approximately 500 known cases worldwide. Pharmacotherapy for ALPS patients generally targets autoimmune cytopenias associated with the disorder. When standard therapies for ALPS-related cytopenias fail, clinicians are often forced to consider novel treatment options. Our patient had ALPS-related thrombocytopenia that was treated with romiplostim, which resulted in grade 3 maculopapular rash after almost 1 year of treatment. The likelihood that this patient's erythematous rash was due to romiplostim administration was determined to be possible based on the Naranjo probability scale. The reaction was reported to the drug manufacturer and to the Food and Drug Administration's MedWatch program. This is the first documented case, to our knowledge, of severe maculopapular rash occurring less than 24 hours after romiplostim administration for treatment of ALPS-related chronic thrombocytopenia. Rash has been reported as an adverse event of romiplostim therapy at higher doses (750 μg), but not at a dose of 500 μg. This report also describes successful rechallenge of romiplostim after resolution of the rash.

Agranulocytosis Induced by Proton Pump Inhibitors; Two Cases of Fatal Antimalarial-Induced Cardiomyopathy; Oxaliplatin-Induced Thrombotic Thrombocytopenic Purpura; Unique Skin Eruption Caused by Telaprevir; Acute-Onset Opioid-Induced Hyperalgesia in a Child; Risk of Sharing a Pill Cutter; Dementia and Risk of Adverse Warfarin-Related Events in Nursing Homes; Comparative Rates of Adverse Events with Parenteral Formulations of Iron

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.

Energy Drinks: Food, Dietary Supplement, or Drug?

Recently, energy drinks/products have enjoyed increased popularity. Although commonly viewed as beverages or food products by consumers, the primary ingredient, caffeine, is considered both a food additive and a drug by the US Food and Drug Administration (FDA).1 The caffeine content in a typical 5 ounce cup of coffee ranges from 60 to 100 mg.1 In energy products, the caffeine content varies greatly, from 47 mg to 80 mg per 8 ounces to as high as 207 mg per 2 ounces.2 Some of the reported adverse effects associated with energy drinks are known reactions to caffeine (eg, anxiety, nausea). However, the role of co-ingredients as risk factors or confounders has not been established. In the November 2012, the FDA announced an ongoing investigation based on recent reports of significant injury or death associated with products marketed as “energy drinks.”3 Summarized data from voluntary reports received by the FDA from January 1, 2004 through October 23, 2012 revealed that adverse events ranged from nonserious (eg, nausea, vomiting, anxiety, and flushing) to significant or serious (eg, renal failure, seizures, arrhythmias, or death).4,5 As is the case with all voluntary adverse event reporting to the FDA, data may be incomplete, causality is not definitive, under- or over-reporting may exist, and the number of reports does not indicate incidence. Yet, based on what appears to be a potential problem, investigation is warranted. In the time before the investigation is completed and conclusions are established, health care professionals should be cognizant of the potential risks associated with these products and patients should be educated. Use in patients with underlying risk factors (eg, cardiac disorders, anxiety) or improper use may be associated with an increased potential for developing adverse events. Of particular importance is the use of these products by young people. Currently, the American Academy of Pediatrics does not recommend the use of caffeine in children because of potential harmful adverse effects and detrimental effects on development.6 A short educational document by the FDA entitled “Caffeine and Your Body,” may be a useful tool in educating parents and patients at risk.1 In addition, health care providers (HCPs) are encouraged to query patients in routine medication histories regarding caffeine use, including beverages, nonprescription products, and dietary supplements. To confound the issue, some energy products (eg, 5-Hour Energy, Monster Energy, Rockstar) are marketed as dietary supplements, while others (eg, RedBull) are marketed as conventional foods.4,5 Although the FDA regulates both dietary supplements and conventional foods under the Federal Food, Drug, and Cosmetic Act (FFDCA), the requirements for these products are different, including the process for marketing and reporting of adverse events post marketing. As noted by the FDA, “A food additive cannot be used in conventional food unless it has been approved for that use by the FDA. However, substances that are generally recognized as safe by qualified experts are not considered to be food additives, and therefore be added to conventional foods without preapproval from the FDA.”3 Dietary ingredients or dietary supplements also do not undergo a FDA approval process, but under the Dietary Supplement Health and Education Act of 1994 (DHSEA) manufacturers of such products are responsible for ensuring that a dietary supplement or ingredient is safe prior to marketing and that labeling is not misleading.7 Even though the manufacturer is not required to register the product with the FDA, all processes related to manufacturing, packaging and labeling should meet good manufacturing standards. To remove a dietary supplement from the market, the FDA must prove that it is unsafe under the conditions of the labeling.3 In light of the recent events and the inconsistency in labeling of energy products, it is essential that HCPs, particularly pharmacists, become involved in the education of patients regarding their use and risks. In addition, regardless of the labeling of food or dietary supplements, HCPs are reminded that their role is essential in the identification of adverse events related to these products with subsequent reporting to the FDA’s MedWatch program.

Ranolazine-Induced Severe Bladder Hypotonia; Fatal Varicella-Zoster Vasculopathy Associated with Adalimumab Therapy; SIADH Induced by a Single Dose of Cyclophosphamide; Tetany, Hypomagnesemia, and Proton Pump Inhibitors; Unnecessary Surgery for Acute Abdomen Caused by ACE Inhibitor Use; Atazanavir-Associated Renal Stones and Biliary Stones; Drug-Induced Hallucinations Associated with Amantadine and Tizanidine

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).

Asystole after First Dose of Ceftriaxone; Nifedipine XL–Induced Dysuria; Duloxetine-Induced Lymphocytic Colitis; Duloxetine-Associated Tardive Dyskinesia; Minocycline-Induced Fulminant Intracranial Hypertension; Voriconazole-Associated Phototoxic Effects; Levetiracetam-Induced DRESS Syndrome; Antipsychotics and Antidepressant Use during Pregnancy

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.

Don’t get burned by OTC topical analgesics

Some consumers have reported receiving serious skin injuries while using certain OTC topical pain relievers to relieve mild muscle and joint pain, FDA has warned. When these products are applied to the skin, they should produce a local sensation of warmth or coolness; they should not cause pain or skin damage. The reported cases of skin injuries ranged from first- to third-degree burns, often following one application of the product.

Ogilvie's Syndrome during High-Dose Methotrexate Chemotherapy: Bevacizumab-Induced Severe Thrombocytopenia: Clozapine-Associated Colitis: Clindamycin-Induced Ageusia, Xerostomia, and Burning Mouth Syndrome: Calcineurin-Inhibitor Pain Syndrome: Exanthematous Drug Eruptions: Angioedema as an Adverse Event of Renin-Angiotensin System Inhibitors: Ocular Adverse Effects of Systemic Treatment with Isotretinoin: Anaphylaxis

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.

Rectal Bleeding and Hemostatic Disorders Induced by Dabigatran; Severe Coagulopathy Caused by Rifampicin in Patients with Sclerosing Cholangitis; Fatal Case of Adynamic Ileus following Initiation of Clozapine; Posttraumatic Memories Triggered by Donepezil in a Dose-Dependent Pattern; Risk of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy; Behavioral Adverse Effects of Antiepileptic Drugs in Epilepsy; Amiodarone-Associated Optic Neuropathy; Factors Associated with Reported Preventable Adverse Drug

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.

Fluoroquinolone-Induced Tendinopathy of the Hip: Metformin-Associated Lactic Acidosis Masquerading as Ischemic Bowel: DRESS Syndrome and Myocardial Death in Patient Treated with Sulfasalazine: Immediate Hypersensitivity Reaction Induced by Metronidazole: Rhabdomyolysis Associated with Kava Ingestion: Azithromycin and the Risk of Cardiovascular Death: Minimizing Inappropriate Medications in Older Populations: An Excellent Framework

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.

Senna-Containing Laxatives Induce Severe Dermatitis in Toddlers: Status Epilepticus Associated with Long-acting Methylphenidate in a Child: Severe Hyperthermia after Administration of Methylphenidate: Panniculitis and Arthralgia in Melanoma Patients Treated with BRAF Inhibitors: Severe Babesiosis Associated with Tumor Necrosis Factor α Antagonist: Catatonia and Encephalopathy Associated with Paliperidone Palmitate: Pulmonary Toxicity after Bortezomib Treatment

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.

Ovarian Toxicity from Sirolimus; Fatal Acute Pulmonary Injury Associated with Everolimus; Injection Site Abscess with Depot Risperidone Injection; Falls Caused by Multiple Medications in Young and Old Patients; Peripheral Nerve Toxic Effects of Nitrofurantoin; Benzodiazepine Withdrawal; Hyponatremia with SSRIs: Are We Getting It?

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.

Mesalazine-Induced Interstitial Nephritis; Psychiatric Drug-Induced Fatal Abdominal Compartment Syndrome; Severe Pelvic Organ Prolapse following Initiation of High-Dose Glucocorticoids; Vancomycin-Induced Severe Neutropenia and Rechallenge Leading to Agranulocytosis; Fatalities Associated with Sodium Phosphate Enemas; Prochlorperazine and Akathisia; Nocturnal Leg Cramps and Preceding Drug Use; Distressing Adverse Events with Citalopram and after Antidepressant Switch; Adverse Drug Reaction Deaths in the United States, 1999-2006

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.

DRESS Syndrome Associated with Deferasirox Treatment Recurrent Stress Cardiomyopathy Induced by Over-the-Counter Phenylephrine; Angular Cheilitis after Selective Serotonin Reuptake Inhibitor Treatment; Chemotherapy-Induced Spontaneous Orgasms; Liraglutide-Induced Acute Kidney Injury; Peripheral Edema Associated with Risperidone; Risk of Bleeding with Concurrent Use of Antibiotics and Warfarin

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. Shuster at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-947-7797; fax: 215-914-1492; e-mail: joel.shuster@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.

Retrieval Studies in Orthopaedic Surgery: Editorial Comment: Learning Every Implant’s Story

Retrieval Studies in Orthopaedic Surgery: Editorial Comment: Learning Every Implant’s Story

Bevacizumab-Induced Laryngeal Necrosis Olanzapine-Related Hyperosmolar Hyperglycemic Syndrome Dangerous Fruit Juice Drug-Induced Hypertension Drug-Induced Pancreatitis Anticoagulation-Associated Adverse Drug Events Severe Cutaneous Adverse Reactions to Antiepileptic Drugs in Asians

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.

Monitoring adverse drug reactions across a nationwide health care system using information technology

The improvement and linkage of two Department of Veterans Affairs (VA) databases for monitoring adverse drug reactions (ADRs) are described, with a discussion of the potential implications for improved medication safety within the VA health care system. Before 2007, VA had limited capability to track and evaluate ADRs across its nationwide network of health care facilities. Since then, VA has established a standardized monitoring system that has improved the reporting, analysis, and trending of ADRs reported by providers and pharmacists at individual VA facilities. The enhanced system has two components with distinct but complementary functions: the Adverse Reaction Tracking database, which is derived by extracting text-based, patient-specific information entered into the VA electronic medical record system by clinicians at the point of care; and the VA Adverse Drug Event Reporting System (VA ADERS), an external web-based portal that contains aggregated data from 146 VA facilities, with standardized coding of reported events. Both databases allow for ADR reporting at the local, regional, and national levels. The VA ADERS database permits rapid electronic reporting of certain ADRs to the federal MedWatch program. The two databases can be used in tandem for more comprehensive assessments of ADR patterns and reporting rates and to generate a wide range of benchmarking data. In recent years, the refinement of two databases for ADR reporting has increased VA's capability to systematically monitor, track, and report ADRs across its national network of health care facilities. Linking the two databases has further strengthened those capabilities, enhancing medication safety practices and aiding in pharmacovigilance.

Anaphylactic Shock Due to Intravenous Amiodarone; Delusional Parasitosis Associated with Donepezil; Connubial Androgenetic Alopecia; Ciprofloxacin-Induced Torsade de Pointes; Postvaccination Miller Fisher Syndrome; Life-Threatening Anaphylactoid Shock Caused by Recombinant Tissue Plasminogen Activator; Thiazide-Induced Hyponatremia

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.

Antiretroviral Prophylaxis and the Risk of Cleft Lip and Palate: Preliminary Signal Detection in the Food and Drug Administration's Adverse Events Reporting System Database

Antiretroviral prophylaxis has been found to be effective in preventing vertical HIV transmission to the offspring of infected mothers. Because medicine and the art of public health require benefits to outweigh any plausible risks, our study aimed to explore and quantify preliminary associations between antiretroviral medications and clefting. We analyzed 5 years of available data from the Food and Drug Administration's Adverse Events Reporting System (Medwatch program) and calculated reporting odds ratios (RORs) and their associated 95% confidence intervals (CIs). The medications with the highest effects were efavirenz with an ROR of 196 (95% CI, 86 to 447), lamivudine with an ROR of 60.2 (95% CI, 14.25 to 148), the combination abacavir sulfate/lamivudine/zidovudine with an ROR of 59.3, and nelfinavir with and ROR of 50.5, followed by nevirapine, lopinavir/ritonavir, and lamivudine/zidovudine. Given the multifactorial etiology of cleft lip and palate, further studies are needed to assess the relative safety of antiretroviral prophylaxis and the specific conditions or potential synergies that might lead to the development of this defect.

Panic Attack Induced by Single Dose of Prednisone;Intracranial Hemorrhage after High-Dose Methylprednisolone;Atrial Flutter Associated with Carboplatin Administration;Hyperosmolar Hyperglycemic State Associated with Ziprasidone;DRESS Syndrome Associated with Antibiotic Therapy;Accidental Polydipsia and Hyponatremia from Diphenhydramine;Reversible Posterior Leukoencephalopathy Syndrome (RPLS) Associated with Ustekinumab Therapy

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.

Dabigatran-lnduced Rash/Type B Lactic Acidosis Associated with Carboplatin Therapy/Sunitinib-Induced Hyperammonemic Encephalopathy/Virilization from Partner's Use of Topical Androgen/Psychosis Associated with Synthetic Cannabinoid Agonists/Drug-Induced Yawning Cardiovascular Medications and Risk of Cancer

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.