Reporting on Adverse Clinical Events

Neutropenia.

In a retrospective review, the incident rate of neutropenia and potential clinical factors were evaluated in 67 adult inpatients receiving at least 7 days of ceftaroline therapy. Adult patients were from 2 large medical centers and treated with the drug over approximately a 4.3-year period (November 2010 to March 2015). Approximately less than half (42%) of the patients were male, and the median age was 50 years (interquartile range = 38-67 years; range = 24-93 years). The most frequently cited indications included bloodstream infections or infective endocarditis (48%), bone and joint infections (33%), pneumonia (16%), and meningitis (3%). Neutropenia was defined as an absolute neutrophil count of 1800 cells/mm³ or less and ranked as mild (1000-1800 cells/mm³), moderate (500-1000 cells/mm³), or severe (<500 cells/mm³). The overall rate of neutropenia in this study was 10% to 14% with at least 2 weeks of therapy and 21% with at least 3 weeks of therapy. The median duration of ceftaroline exposure was 26 days (interquartile range = 22-44; range = 13-68) in patients who developed neutropenia and 15 days (interquartile range = 9-29; range = 7-64) in patients without neutropenia (P = .048). There was no association between incident neutropenia and several factors including age, gender, prior antibiotic allergies, renal dysfunction, or body mass–adjusted ceftaroline doses.

The authors concluded that in this study the overall rate of neutropenia was between 10% and 14% and related to the duration of ceftaroline therapy and the number of doses received.

Ceftaroline [“Teflaro”]

Furtek KJ et al (KJ Furtek, School of Pharmacy, Northeastern University, Boston, MA; e-mail: kfurtek@gmail.com) High incidence of neutropenia in patients with prolonged ceftaroline exposure. J Antimicrob Chemother 71:2010–2013 (Jul) 2016

FDA Safety Communication: Cardiovascular Risk.

On June 7, 2016, the US Food and Drug Administration (FDA) alerted health care professionals and patients that taking higher than recommended doses of loperamide has resulted in serious and potentially fatal cardiovascular outcomes, including arrhythmias. The majority of serious reports occurred in individuals misusing/abusing the product to treat opioid-withdrawal symptoms or to achieve a “high.” This safety communication was based, in part, from data gleaned from a published literature and a search of the FDA Adverse Event Reporting System database from the drug’s initial approval (1976) through the end of 2015. Several case reports have been published in the literature regarding cardiovascular events associated with loperamide use, both with excessive amounts and in therapeutic doses. Three reports were fatal. The FDA Adverse Event Reporting System search identified 48 cases of serious cardiac events with loperamide use with the most frequently reported cardiac events as syncope (n = 24), cardiac arrest (n = 13), QT interval prolongation (n = 13), ventricular tachycardia (n = 10), and torsades de pointes (n = 7). Ten of these cases were fatal, and 9 of the fatal reports indicated that the deaths were related to ingestion of large amounts of loperamide. Approximately half (22/48) of the case reports were in patients ingesting high doses in abuse of the drug; 17 cases were in patients taking the drug for the treatment of diarrhea. Where data were available, the mean dose was 195 mg daily (range = 1-1600 mg daily), and the duration ranged from less than 1 day to 18 months. Two cases involved children younger than 2 years, in whom loperamide use is not recommended. In several cases, patients were also taking concurrent therapy with drugs that are cytochrome P450 or P-glycoprotein inhibitors (eg, quinidine), which may interfere with the metabolism of the drug and increase the blood levels and the effects of loperamide. In patients who were abusing/misusing the drug, torsades de pointes was frequently reported. However, syncope and ventricular tachycardia events occurred in patients receiving therapeutic doses of loperamide. Additional data, summarized from US poison control call centers (since 2006), noted increased calls regarding intentional loperamide exposures, including intentional abuse, intentional misuse, suspected suicide attempts, and unknown intentional exposures. It was suggested that the numbers summarized in this review may be low as testing for loperamide is not included in routine toxicology testing and, thus, may not be recognized in these events.

Loperamide [“Imodium”]

FDA Drug Safety Communication: FDA warns about serious heart problems with high doses of the antidiarrheal medicine loperamide (Imodium), including from abuse and misuse. http://www.fda.gov/Drugs/DrugSafety/ucm504617.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Jun 7) 2016

FDA Public Notification: Hidden Drug Ingredient.

On June 6, 2016, the US Food and Drug Administration (FDA) alerted health care professionals and patients regarding a hidden drug ingredient in a dietary supplement (Exhilarate) promoted for weight loss. A laboratory analysis of the product confirmed that it contained sibutramine, desmethylsibutramine, and phenolphthalein. Sibutramine and desmethylsibutramine are structurally similar; sibutramine was removed from the US market in October 2010 related to safety reasons. Use of these agents has been associated with hypertension and tachycardia and could result in significant adverse events in patients with underlying cardiac disease. Phenolphthalein was withdrawn from the US market. This notification from the FDA is a reminder that there is a trend of hidden drugs and chemicals in dietary supplements or conventional foods. Most of these products are promoted as natural, are available on the Internet, and are promoted for sexual enhancement, weight loss, and bodybuilding. Patients need to consider possible issues with hidden or undeclared ingredients when purchasing these agents.

Natural Supplement [“Exhilarate”]

Public Notification: Exhilarate contains hidden drug ingredients. http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/MedicationHealthFraud/ucm505202.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Jun 6) 2016

FDA Drug Safety Communication: Serious Bleeding Risk.

On June 6, 2016, the US Food and Drug Administration (FDA) alerted health care practitioners and patients regarding the risk of serious bleeding when using aspirin-containing antacid products to treat various gastrointestinal symptoms. Though many of the product labeling already contains information regarding bleeding risk, there has been continued reports of this issue associated with use. This new communication was in part based on the identification of reports from search of the FDA Adverse Event Reporting System database (1969-2014). This review identified 41 cases of serious bleeding events reported with nonprescription products containing aspirin, sodium bicarbonate, and citric acid. All reports described serious outcomes resulting in hospitalization, and 21 patients required transfusions due to hemorrhage. The majority of patients recovered; there was one death reported in this review of material. Of these cases, 11 documented the routine use of product within recommended doses. Factors associated with increased risk of bleeding include age (≥60 years), history of gastric ulcers or bleeding problems, concurrent therapy with anticoagulants or steroids, nonsteroidal anti-inflammatory agents, alcohol use (≥3 drinks daily), excessive use, or excessive duration of use.

Aspirin-Containing Antacids [“Alka-Seltzer Original,” “Bromo Seltzer,” “Medique Medi Seltzer,” “Picot Plus Effervescent,” “Vida Mia Pain Relief,” “Winco Foods Effervescent Antacid and Pain Relief,” “Zee-Seltzer Antacid and Pain Reliever”]

FDA Drug Safety Communication: FDA warns about serious bleeding risk with over-the-counter antacid products containing aspirin. http://www.fda.gov/Drugs/DrugSafety/ucm504328.htm (Jun 6) 2016

Severe Hypocalcemia.

A 63-year-old female patient developed generalized weakness, difficulty walking, peripheral and perioral paraesthesia, hand cramps, and tremors approximately 10 days after receiving a fourth dose of subcutaneous denosumab (60 mg every 3 months) for the treatment of osteoporosis. Medical conditions included stage 5 chronic kidney disease, arthritis, secondary hyperparathyroidism, and osteoporosis. Concurrent medication included calcitriol (0.25 µg 3 days weekly). Previous treatment for osteoporosis included an oral bisphosphonate 7 years prior to this event, which was switched to raloxifene for 4 years prior to starting denosumab. A physical examination on admission revealed Chvostek sign and Trousseau sign, with generalized muscle weakness. An electrocardiogram revealed a prolonged QTc interval. Abnormal laboratory values included serum creatinine (338 µmol/L), corrected calcium (1.28 mmol/L), and parathyroid hormone (93 pmol/L). A previous serum-corrected calcium had been within the normal range on routine monitoring 2 months prior to this event (2.26 mmol/L). The patient was admitted to an intensive care unit. Calcitriol and denosumab were discontinued. Treatment included intravenous calcium replacement, which resulted in normalizing serum calcium. The patient was discharged on oral calcium.

The authors concluded that this patient experienced severe hypocalcemia related to denosumab therapy based on the temporal relationship between the administration of the drug and the appearance and resolution of symptoms. Previous cases have been reported in patients with chronic renal disease. They noted that chronic renal disease may be a contributing factor as there is reduced levels of 1,25-OH vitamin D levels, which can result in reduced intestinal absorption of calcium.

Denosumab [“Xgeva”]

Killen JP et al (JP Killen, Department of Renal Medicine, Prince of Wales Hospital, Sydney, New South Wales, Australia) Life-threatening hypocalcaemia associated with denosumab in advanced chronic kidney disease. Intern Med J 46:746–747 (Jun) 2016

Risk of Hospitalized Heart Failure in New Users.

A population-based, retrospective, cohort study of adult diabetic (type 2) patients compared the association of hospitalized heart failure in new users of saxagliptin and sitagliptin with new users of second-generation sulfonylureas, pioglitazone, or long-acting insulin products. The study was conducted as part of a Mini-Sentinel FDA program involving data from 18 heath insurance and health system data partners. The gender and age distribution were similar between the groups with slightly more than half being male (55%) and a mean age approximately 60 years. The mean follow-up period for users of insulin and saxagliptin was 4 months and 7 months, respectively. For users of sitagliptin, pioglitazone, and sulfonylureas, the mean follow-up was about 7 to 8 months. The rate of hospitalized heart failure per 1000 person-years ranged from 2 to 4 for saxagliptin, 3 to 7 for sitagliptin, 4 for pioglitazone, 9 for sulfonylurea, and 16 for insulin groups. The risk for hospitalized heart failure was significantly different with the saxagliptin and saxagliptin when compared with the other groups. The hazard ratios from the disease risk score–stratified analyses were 0.83 (95% confidence interval = 0.70-0.99) for saxagliptin versus sitagliptin, 0.63 (confidence interval = 0.47-0.85) for saxagliptin versus pioglitazone, 0.69 (confidence interval = 0.54-0.87) for saxagliptin versus sulfonylureas, and 0.61 (confidence interval = 0.50-0.73) for saxagliptin versus insulin. Prior cardiovascular disease did not affect the risk of hospitalization for heart failure.

The authors concluded that in this study saxagliptin and sitagliptin were not associated with an increased risk for hospitalized heart failure compared with pioglitazone, second-generation sulfonylureas, or long-acting insulin products.

Sitagliptin [“Januvia”]

Saxagliptin [“Onglyza”]

Toh S et al (S Toh, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, 401 Park Drive, Suite 401, Boston, MA 02215; e-mail: darren_toh@harvardpilgrim.org) Risk for hospitalized heart failure among new users of saxagliptin, sitagliptin, and other antihyperglycemic drugs: a retrospective cohort study. Ann Intern Med 164:705–714 (Jun) 2016

Tachycardia With Overdose.

A 23-year-old female patient was hospitalized approximately 3 hours after an intentional overdose ingestion with extended-release paliperidone (504 mg; 55 × 9 mg tablets), immediate-release quetiapine (400 mg), and zopiclone (15 mg). The ingestion of alcohol or other medications were denied. On admission, the patient was drowsy and the heart rate and blood pressure were slightly elevated (96 bpm and 130/70 mm Hg, respectively). Other laboratory values were within normal limits. An electrocardiogram revealed sinus tachycardia (110 bpm) without conduction abnormalities. Ten hours post-supine was 95 mm Hg. Repeated electrocardiograms revealed narrow-complex tachycardia (up to 190 bpm) with a prolonged absolute QT interval (320 ms). Treatment included the administration of intravenous crystalloid, magnesium, and potassium. The tachycardia persisted for approximately 72 hours (maximum rate = 190 bpm at 40 hours postingestion). Quetiapine serum presence was not detected. Serum paliperidone concentrations at 4 hours and 40 hours postingestion were 29 and 883 ng/mL, respectively. The patient was eventually discharged. Heart rate was 100 bpm without conduction abnormalities at discharge. Follow-up status was not provided.

The authors concluded that this patient experienced persistent tachycardia associated with an intentional overdose of extended-release paliperidone.

Paliperidone XR [“Invega Sustenna”]

Wong LY et al (LY Wong, Austin Health, Austin Hospital Emergency Department, Victorian Poisons Information Centre, Heidelberg, Australia; e-mail: leeyungwong@gmail.com) Severe prolonged posture-evoked tachycardia after massive overdose of paliperidone. Clin Toxicol (Phila) 54:535 (Jun) 2016

Medication Error.

As a result of a medication error, a 52-year-old female patient inadvertently received manganese chloride (800 mg/4 mL) instead of magnesium chloride (800 mg) during an elective outpatient intravenous chelation regimen for lead toxicity (lead concentration = 3.0 lg/dL). The prescribed intravenous regimen included calcium disodium ethylenediaminetetraacetic acid (2.5 g), vitamin C, heparin, potassium chloride, vitamin B₁, vitamin B₅, vitamin B₆, sodium bicarbonate, N-acetylcysteine, glutathione, and magnesium chloride (800 mg). Typical manganese doses are less than 500 µg/day. Initial symptoms began during the infusion (eg, flushing) and the patient was transported to a hospital for evaluation. Although the patient was initially asymptomatic, administration of an excessive dose of a known neurologic toxicant required evaluation and treatment. Two, 4-hour hemodialysis sessions were initiated at 7 and 21 hours following the manganese infusion. After hemodialysis was completed, additional treatment included the administration of calcium disodium ethylenediaminetetraacetic acid (1 g/m² over 8 hours). The initial whole blood manganese concentration obtained 6 hours after exposure and before treatment was initiated was increased (120 µg/L or 2.19 µmol/L) but was reduced afger hemodialysis (20 µg/L or 0.36 µmol/L). The extraction ratio from hemodialysis ranged from 0.28 at onset to 0.10 at hemodialysis conclusion. Analysis of dialysate from the first hemodialysis session revealed a limited elimination of manganese (604 µg). Magnetic resonance imaging indicated manganese exposure and distribution to the central nervous system. The patient was discharged on hospital day 5; the whole blood manganese concentration was 2.2 µg/L (0.04 µmol/L) at that time. At a 1-month postdischarge follow-up assessment, findings on a repeat magnetic resonance imaging showed no changes. At 9 months postdischarge, magnetic resonance imaging findings were stable and the patient reported no symptoms.

The authors concluded that this patient experienced reversible symptoms with manganese poisoning due to inadvertent administration of the agent related to a medication error. In this case, hemodialysis did not significantly enhance elimination of the product.

Manganese [Manganese]

Hines EQ et al (EQ Hines, New York City Poison Control Center, 455 First Avenue, Room 123, New York, NY 10016; e-mail: LizquaaL@gmail.com) Massive intravenous manganese overdose due to compounding error: minimal role for hemodialysis. Clin Toxicol (Phila) 54:523–525 (Jun) 2016

Risk of Intracranial Hemorrhage.

In a meta-analysis of 7 randomized controlled trials, the association between higher dose of selected statins and risk of intracranial hemorrhage among patients with cardiovascular disease was studied. The 7 randomized controlled trials included 31 099 subjects who received high-dose statin and 31 105 subjects who received placebo. High dose of statins included atorvastatin 80 mg daily, simvastatin 80 mg daily, pravastatin 40 mg daily, and rosuvastatin 20 mg daily. A significant risk of intracerebral hemorrhage was observed in patients receiving high dose of statin (relative risk = 1.53; 95% confidence interval = 1.16-2.01; P = .002). No significant heterogeneity or publication bias was observed. There was no difference in all-cause mortality between the 2 groups (relative risk = 0.95; 95% confidence interval = 0.86-1.06; P = .36). A significant heterogeneity was observed (v₂ = 21.04; pHet = 0.0002, I₂ = 71%).

The authors suggested that this study demonstrated an increased risk of intracranial hemorrhage associated with high-dose statin. They also recognized that further study is needed to confirm these findings.

Atorvastatin [“Lipitor”]

Pravastatin [“Pravachol”]

Rosuvastatin [“Crestor”]

Simvastatin [“Zocor”]

Pandit AK et al (AK Pandit, Department of Neurology, Neurosciences Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India; e-mail: akpandit.med@gmail.com) High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis. Acta Neurol Scand 134:22–28 (Jul) 2016

Risk of Adverse Events With Coprescriptions.

In a population-based cohort study using data from Taiwan’s National Health Insurance database of 32 801 patients treated between 1997 and 2011 with coprescriptions of statins and calcium channel blockers that inhibit cytochrome 3A4 (amlodipine, diltiazem, felodipine, nicardipine, nifedipine, and verapamil). The patients were separated into 2 groups matched for age, gender, and comorbidity and according to CYP3A4-metabolized statins (lovastatin, simvastatin, and atorvastatin) or non-CYP3A4-metabolized statins (fluvastatin, rosuvastatin, and pitavastatin). A total of 5857 patients received coprescription of CYP3A4-metabolized statins and calcium channel blockers that inhibit CYP3A4. The same number received CYP3A4-metabolized statins and calcium channel blockers that did not inhibit CYP3A4. The mean age of the group was 62.72 years, and approximately 52% were male. When compared to patient who did not receive CYP3A4-metabolized statins, patients who did receive CYP3A4-metabolized statins had significantly higher risk of acute kidney injury (adjusted odds ratio = 2.12; 95% confidence interval = 1.35-3.35), hyperkalemia (adjusted odds ratio = 2.94; 95% confidence interval = 1.36-6.35), acute myocardial infarction (adjusted odds ratio = 1.55; 95% confidence interval = 1.16-2.07), and acute ischemic stroke (adjusted odds ratio = 1.35; 95% confidence interval = 1.08-1.68). However, there was no significant difference between the 2 groups for the risk of acute liver failure or mortality.

The authors concluded that this nationwide cohort study demonstrated an increased risk of certain adverse events following the coprescription of CYP3A4-metabolized statins and calcium channel blockers that inhibit CYP3A4.

Statins [“Lipitor,” “Zocor,” “Crestor,” “Pravachol,” “Lescol,” “Mevachol,” “Livalo”]

Calcium Channel Blockers [“Amlodipine,” “Diltiazem,” “Felodipine,” “Nicardipine,” “Nifedipine,” “Verapamil”]

Wang YC et al (TC Fang, Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111, Section 3, Hsing-Long Road, Taipei 116, Taiwan; e-mail: fangtechao@yahoo.com.tw) Risks of adverse events following coprescription of statins and calcium channel blockers: a nationwide population-based study. Medicine (Baltimore) 95:e2487 (Jan) 2016

Bullous Eruption.

A 57-year-old woman developed an erythematous plaque after 11 days of treatment with intramuscular meglumine antimoniate (60 mg/kg/day) for the management of cutaneous leishmaniosis. The plaque occurred on the left leg adjacent to the injection site followed by a vesicular-bullous eruption not at the injection site (eg, left-lower-abdominal quadrant). No other medications were mentioned in the report. Treatment included the discontinuation of meglumine antimoniate, which resulted in spontaneous resolution 3 days later without pigmentation changes. A cutaneous biopsy revealed necrotic keratinocytes in the epidermis, edema, and sparse perivascular inflammatory infiltrates in the papillary epidermis. In addition, pentamidine (4 mg/kg) was substituted without further event. No abnormalities in laboratory values were observed. After recovery, intradermal tests with 1/10 and 1/100 meglumine antimoniate dilutions demonstrated positive but delayed dermal reactions after 48 and 96 hours. At follow-up 8 months later, no further dermal changes were noted.

The authors concluded that this patient experienced localized bullous eruption related to meglumine antimoniate injections based on the temporal relationship between the administration of the drug and the appearance and resolution of the symptoms. According to the Naranjo probability scale, this reaction was rated as probable in relation to the drug. Possible mechanisms of action included local drug toxicity associated with extravasation of the solution near the injection site in addition to an immunoallergic reaction that occurred away from the site.

Meglumine Antimoniate [Meglumine Antimoniate]

Ben Salem C et al (C Ben Salem, Department of Pharmacovigilance, Sousse, Tunisia) Localized bullous eruption away from injection site, caused by intramuscular meglumine antimoniate administration. Ann Pharmacother 50:517–518 (Jun) 2016

FDA Safety Communication: Burns Associated With Use.

On June 6, 2016, the US Food and Drug Administration (FDA) announced to health care professionals and the public regarding the initiation of an investigation into reports describing serious burns and potential permanent scarring with the use of sumatriptan iontophoretic transdermal patch for the treatment of migraine headaches. Since marketing of the patch in September 2015, the FDA has received a large number of reports in which patients experienced burns or scars on the patch location. Specific symptoms included severe redness, pain, skin discoloration, blistering, and cracked skin. Based on these reports, the FDA is evaluating the reports to determine if regulatory action is needed. The safety communication also noted that patients who experience moderate to severe pain at the patch site should immediately remove the patch to avoid the possible described symptoms. The patch should be removed in these situations without regard to the duration of patch use. Instructions for use of the patch also detail that the patient not bathe, shower, or swim while wearing the patch. Health care professionals are encouraged to advise patients to remove the patch immediately in the event of moderate to severe pain at the application site. The patch delivery system delivers a dose via a single-use, battery-powered patch that is wrapped around the upper arm or thigh. Patients and health care givers are also encouraged to report any adverse events associated with use of this product.

Sumatriptan, Transdermal [“Zecuity”]

FDA Drug Safety Communication: FDA evaluating the risk of burns and scars with Zecuity (sumatriptan) migraine patch. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM504722.pdf (Jun 2) 2016

Adverse Events.

In a recent publication, a comprehensive search of the published literature was performed to evaluate, review, and summarize the adverse effects that have been reported after intravenous lipid emulsion administration irrespective of the indication (ie, nutrition, drug carrier, or treatment of poisoning). The purpose of this review was to offer data that would assist clinicians in determining a risk/benefit assessment when intravenous lipid emulsions are used for the treatment of various poisonings. Experimental studies and reports of adverse effects as a result of long-term therapy (>14 days) were excluded. The initial search identified 36 903 citations, of which 789 were full-text articles. Of these, 114 met the study criteria. A total of 27 were animal studies; 87 were considered human studies. In this review, the adverse effect profile associated with acute intravenous lipid emulsion administration included acute kidney injury, cardiac arrest, ventilation perfusion mismatch, acute lung injury, venous thromboembolism, hypersensitivity, fat embolism, fat overload syndrome, pancreatitis, extracorporeal circulation machine circuit obstruction, allergic reaction, and increased susceptibility to infection.

The authors concluded that this review helped identify the published adverse effects associated with intravenous lipid emulsion administration. The authors noted that the emerging use of this agent in the management of poisonings warrants close monitoring of evolving data regarding potential adverse events. They also noted that the results documented in the review are not to be extrapolated to other clinical toxicology management scenarios and that further study is needed.

Lipid Emulsions, Intravenous [Lipid Emulsions]

Hayes BD et al (BD Hayes, Department of Pharmacy, University of Maryland Medical Center, 22 South Greene St, Baltimore, MD 21230; e-mail: bryanhayes13@gmail.com) Systematic review of clinical adverse events reported after acute intravenous lipid emulsion administration. Clin Toxicol (Phila) 54:365–404 (May) 2016

Agranulocytosis.

A 47-year-old female patient was hospitalized with severe throat pain, difficulty swallowing, and fever during maintenance amisulpride therapy for the treatment of schizophrenia. Examination of the oral cavity revealed an enlarged right tonsil with tonsillar erythema. Other components of the physical examination were unremarkable. Abnormal laboratory values included total white cell count (0.3 × 10⁹/L), absolute neutrophil count (0 × 10⁹/L), hemoglobin (122 g/L), C-reactive protein (444 mg/L), urea (15.8 mmol/L), and creatinine (145 µmol/L). A normal full blood count was documented 2 months prior to admission, with no recent change in medications. Treatment included granulocyte colony stimulating factor administration, which did not reverse the neutropenia. Screenings for infectious and autoimmune etiologies were negative. It was suspected that the reaction was drug induced; thus, amisulpride was discontinued and granulocyte colony stimulating factor was reinitiated. Acyclovir and itraconazole were initiated for antiviral and antifungal prophylaxis. Opiates were started for throat pain; antibiotics were started for suspected infection despite negative cultures. Severe neutropenia persisted for approximately 2 weeks. Granulocyte colony stimulating factor was continued until the neutrophil count increased over 1 × 10⁹/L for 2 consecutive days. Treatment and prophylactic medications were discontinued once the neutropenia reversed. The patient was eventually discharged without further event. Treatment was initiated with flupenthixol and follow-up at 3 months normal hematological screens.

Amisulpride [Amisulpride]

Pickard L et al (L Pickard, Department of Hematology, St George’s University Hospitals NHS Foundation Trust, Blackshaw Road, Tooting SW170QT, London, UK; e-mail: lucypickard@doctors.org.uk) Amisulpride induced agranulocytosis: a case report. Ann Hematol 95:1193–1195 (Jun) 2016

FDA Public Notification: Hidden Drug Ingredient.

On April 26, 2016, the US Food and Drug Administration (FDA) alerted health care professionals and patients regarding a hidden drug ingredient in a dietary supplement (3rd Degree) promoted for the use of weight loss. A laboratory analysis of the product confirmed that it contained sibutramine, which was removed from the US market in October 2010 related to safety reasons. Use of this agent has been associated with hypertension and tachycardia and could result in significant adverse events in patients with underlying cardiac disease. This notification from the FDA is a reminder that there is a trend of hidden drugs and chemicals in dietary supplements or conventional foods. Most of these products are promoted as natural, are available on the Internet, and are promoted for sexual enhancement, weight loss, and bodybuilding. Patients need to consider possible issues with hidden or undeclared ingredients when purchasing these agents.

Natural Supplement [“3rd Degree”]

Public Notification: 3rd Degree contains hidden drug ingredients. http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/MedicationHealthFraud/ucm497831.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Apr 26) 2016