Abstract
Keywords
BACLOFEN No. 144
Acute Psychosis
A 60-year-old male patient with binge eating disorder developed dose-dependent adverse events after starting baclofen for the reduction of food cravings. The dose was progressively titrated to 300 mg daily (60 mg 5 times a day). Concurrent medications included abacavir-lamivudine, nevirapine, telmisartan, rilmenidine, spironolactone, bisoprolol, flecainide, aspirin, and lercanidipine. Initial adverse events included dizziness and nausea at 70 mg daily, and progressed to tachypsychia, cognitive disorders, intermittent short-term memory loss, and irritability at higher doses (180-200 mg daily). After 1 year of treatment, the drug was progressively reduced to 80 mg daily. The patient who lived in France had to obtain the medication in Belgium, which was only available in 10 and 25 mg tablets. Via a medication error with the new medications, the patient was hospitalized 48 hours later with drowsiness and disorientation. These effects progressed to delusions, visual hallucinations, and aggressiveness. The blood baclofen concentration was elevated (562 µg/L), indicative of an overdose. All psychotropic medications were discontinued, including baclofen (300 mg), hydroxyzine (25 mg), and mianserine (10 mg). A half dose of baclofen was restarted based on the assumption that the confusion could be due to the abrupt cessation of baclofen. Approximately 48 hours later, the patient was aware and coherent. Further psychiatric evaluation revealed that there was no indication of a psychiatric disorder. Brain magnetic resonance imaging was normal. Treatment was reinitiated with baclofen without further event.
The authors concluded that this patient developed acute psychotic symptoms associated with baclofen therapy based on the temporal relationship between the administration of the drug and the appearance and resolution of symptoms.
Baclofen [Baclofen]
Ricoux O et al (O Ricoux, CHU Lille, Department of Psychiatry and Addiction Medicine Lille, Lille, France) Acute psychosis related to baclofen in a patient treated for binge eating disorder highlights the urgent need to regulate off-label prescriptions. J Clin Pyschopharmacol 39:282–284 (Jun) 2019
VALSARTAN No. 145
FDA Safety Communication: Update
On May 2, 2019, the US Food and Drug Administration (FDA) announced that they are continuing to investigate the presence of chemical impurities, specifically N-nitrosodimethylamine and N-nitrosodiethylamine in valsartan and other angiotensin II receptor blockers. According to this report, several manufactured products with confirmed levels of N-nitrosodimethylamine or N-nitrosodiethylamine with exceeding the acceptable limits have been recalled. The FDA has noted that several more products have been added to the list of recalled products and that this updated list is maintained on the FDA website. In addition, the specified limits and recent interim modifications are described.
Valsartan [Valsartan]
FDA Safety Communication: Laboratory analysis of valsartan products. https://www.fda.gov/drugs/drug-safety-and-availability/laboratory-analysis-valsartan-products?utm_campaign=UPDATE%20on%20angiotensin%20II%20receptor%20blocker%20%28ARB%29%20recalls-&utm_medium=email&utm_source=Eloqua (May 2) 2019
MEDICATIONS No. 146
Medication Errors Associated With Preadmission Medications for Orthopedic Surgery
A retrospective observational study including 198 patients admitted to an orthopedic unit was performed to evaluate the prevalence and nature of medication errors associated with preadmission medications that occurred in the first 72 hours of admission. Mean age was 70 years (standard deviation = 16.6), and the median number of preadmission medications was 7 (interquartile range = 4-10). Many of the patients (46%) had severe systemic disease with substantial functional limitations (American Society of Anesthesiologists physical status category 3). A total of 176 (88.9%) of included patients experienced one or more errors related to preadmission medications. The median number of errors per patient was 6 (interquartile range = 3-10). Errors most frequently occurred during prescribing (n = 1369, 94.2%), and of these, most were related to unintended omission of a preadmission medication (n = 1196, 87.4%). Seventeen adverse events involving 24 medications and 16 patients (8.1%) were determined as potentially related to an admission medication error. The majority of adverse events were related to an omission or prescribing error. Six events were classified as having moderate clinical consequence, and the remaining 11 were classified as minor. There were no statistically significant differences noted between elective and nonelective patients.
The authors concluded that in this study, medication errors were common in orthopedic patients admitted to the hospital. They further stated that some of these errors resulted in patient harm and interventions to ensure accurate prescribing were important.
Medications [Medications]
Tran T et al (T Tran, Pharmacy Department, Austin Health, 145 Studley Road, Heidelberg, Victoria, Australia; e-mail:
ASPIRIN No. 147
Kounis Syndrome
A 49-year-old woman developed severe chest pain and shortness of breath a couple hours after taking oral aspirin (1 g) for left hip pain. No concurrent medications were reported; however, similar symptoms were reported after taking aspirin or nonsteroidal anti-inflammatory drugs in the past. Heart rate was 100 beats per minute, and blood pressure was 120/70 mm Hg. Physical examination revealed bilateral expiratory lung wheezing. Electrocardiography revealed ST segment elevation in the inferior leads, and chest X-ray was unremarkable. Transthoracic echocardiogram showed kinetic abnormalities of anterolateral and inferior walls, and a left ventricular ejection fraction of 35%. Significant laboratory findings included elevated troponin I (50 ng/mL). Coronary angiogram revealed severe stenosis in the ostium of the right coronary artery and discrete stenosis in the distal left anterior descending artery. Treatment included percutaneous angioplasty and standard medical therapy including aspirin and clopidogrel. A repeat echocardiogram showed improved left ventricular ejection fraction (50%). Over the subsequent month, multiple recurrences of chest pain and asthma attacks occurred. Non-ST-elevation myocardial infarction occurred 1 month later. Repeat coronary angiography revealed a patent left anterior descending stent and severe diffuse stenosis. Sinus tomography and a nasal endoscopy revealed bilateral nasal polypsosis. Further treatment included administration of nitroglycerin and discontinuation of aspirin. Clopidogrel was continued, and no additional asthma attacks or chest pain occurred during the next 2 years of follow-up.
The authors concluded that this case described a combined variant of Kounis syndrome type I and type II related to aspirin exposure. Proposed mechanisms included massive release of chemical substances (tryptase, chymase, histamine) in cardiac tissue, coronary arteries, and plagues by mast cells during immunological reaction to aspirin.
Aspirin [Aspirin]
Hangouche AJE et al (AJE Hangouche, Department of Cardiology B, Ibn Sina Hospital, Mohammad B University, Rabat, Morocco) Kounis syndrome induced by oral intake of aspirin: case report and literature review. Pan Afr Med J 30:301 (Aug) 2018
DIETARY SUPPLEMENT No. 148
FDA Safety Communication: Recall Based on Undeclared Ingredient
On May 6, 2019, the US Food and Drug Administration announced a recall of a dietary supplement sold for male sexual enhancement because it contained an undeclared prescription ingredient, sildenafil. Sildenafil is approved in the United States for the management of erectile dysfunction. The unintended ingestion of this medication may be associated with complications in patients who have hypertension, diabetes, hyperlipidemia, or cardiac disorders. Patients are advised not to purchase this product and, if already purchased, seek the appropriate method of return via the manufacturer.
Dietary Supplement [“BEAST Capsules”]
FDA Safety Communication: STIFF BOY LLC. Issues voluntary nationwide recall of the BEAST Capsules due to presence of undeclared sildenafil. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/stiff-boy-llc-issues-voluntary-nationwide-recall-beast-capsules-due-presence-undeclared-sildenafil?utm_campaign=FDA%20MedWatch~The%20Beast%20Capsules%20by%20STIFF%20BOY&utm_medium=email&utm_source=Eloqua (May 6) 2019
PRASUGREL No. 149
Thrombocytopenia
A 69-year-old male inpatient developed thrombocytopenia after the administration of prasugrel post coronary intervention. Medications on admission included aspirin and clopidogrel; prasugrel was substituted for clopidogrel after the intervention. The platelet count 24 hours after the percutaneous coronary intervention was 40 000/µL, and reached a nadir of 4000/µL within 48 hours. Treatment included the administration of 1 unit of platelets and the discontinuation of heparin. The rapid drop in platelet was evaluated with a heparin-induced thrombocytopenia antibody and serotonin release assay test; both were negative. Laboratory screenings for infectious and immunological etiologies were negative. After prasugrel was also discontinued, the thrombocytopenia slowly improved. Ticagrelor was substituted without further event. On the 10th day post coronary intervention, the platelet count was 153 000/µL. The patient was discharged without further event.
The authors concluded that this patient experienced prasugrel-induced thrombocytopenia based on the temporal relationship between the administration of the drug and the appearance and resolution of symptoms.
Prasugrel [“Effient”]
Hashmi AT et al (AT Hashmi, Departments of Medicine and Cardiology, Maimonides Medical Center, Brooklyn, NY) Prasugrel-induced thrombocytopenia after percutaneous coronary intervention. Am J Ther 26:e425–e426 (May) 2019
FLUOROURACIL No. 150
Cardiotoxicity
A 35-year-old woman developed severe anginal chest pain during the second cycle of weekly chemotherapy including fluorouracil (1600 mg/m2) for treatment of rectal cancer with metastasis to the liver. Concurrent medications included leucovorin (500 mg/m2) and irinotecan (100 mg/m2). Electrocardiography revealed ST elevations. Treatment included discontinuation of fluorouracil. Treatment of cancer was changed to capecitabine (1500 mg a day every 2 weeks with 1 week off), irinotecan (100 mg/m2 on day 1), and bevacizumab (5 mg/kg every 2 weeks). This regimen was continued for 6 months without recurrence of chest pain; however, higher doses of capecitabine caused anginal chest pain and shoulder ache. A computed tomography of the liver after 6 months of treatment showed a significant response to chemotherapy. Further treatment included liver tumor and rectal resection and radiation to the rectal area. Chemotherapy was continued for an additional 3 months without recurrence of chest pain.
The authors concluded that the anginal chest pain described in this case was related to fluorouracil and that low-dose capecitabine was tolerated. Proposed mechanisms for anginal pain included coronary vasospasm and direct cytotoxicity.
Fluorouracil [“Adrucil”]
Peng T et al (T Peng, Hospital of Traditional Chinese Medicine, Keqiao District, Shaoxing City, Zhhejiang Province, China; e-mail:
MESALAZINE No. 151
Acute Myopericarditis
A 45-year-old male patient was hospitalized with severe headache, neck pain, myalgia, arthralgia, rigors, diaphoresis, nausea, and pleuritic central chest pain approximately 2 weeks after starting mesalazine (1500 mg twice daily) for the management of ileocolonic Crohn disease. Concurrent medications included a tapering regimen of prednisolone (40 mg daily for 3 weeks reduced by 5 mg/week to 20 mg daily). A physical examination on admission revealed fever and epigastric tenderness. Abnormal laboratory values included elevated troponin I (381 ng/L) and C-reactive protein (20.7 mg/L). Chest X-ray and computed tomography of the brain were normal. Mesalazine was discontinued. Treatment for suspected meningitis was initiated with intravenous ceftriaxone and acyclovir. Prednisolone was continued; pantoprazole was started. Cerebrospinal fluid was negative for common bacterial and viral pathogens. Serological testing for infectious and immunological etiologies were negative. The headache and fevers resolved by hospital day 2 but mild chest tightness persisted. Antimicrobials were stopped and mesalazine was restarted at the previous dose. On day 3, the chest discomfort worsened. In addition, other symptoms recurred, including neck pain, nausea, arthralgia, and diaphoresis. Troponin levels, which had decreased to 124 ng/L prior to these changes, increased to 516 ng/L. A transthoracic echocardiogram showed mid-todistal posterior hypokinesis and a globally thickened pericardium. Mesalazine was discontinued on day 4 and symptoms resolved by day 5. Troponin levels decreased to 100 ng/L. The patient was discharged without further event. At follow-up, 10 months later while on azathioprine, there were no further events.
Based on the temporal relationship between the administration of the drug and the appearance and resolution of symptoms, the authors concluded that this patient experienced myopericarditis related to mesalazine therapy.
Mesalazine [Mesalazine]
Downton TD et al (TD Downton, Division of Medicine, Royal Darwin Hospital, Darwin, Northern Territory, The Canberra Hospital, Canberra, ACT, Australia). Acute myopericarditis in a patient recently started on mesalazine for Crohn disease. Intern Med J 49:676–677 (May) 2019
CANNABIS No. 152
Cyclical Vomiting Syndrome–Related Hospitalizations
A retrospective review of all Colorado hospital admissions due to cyclical vomiting syndrome–related to cannabis use between 2010 and 2014 were evaluated. Evidence revealed that there was a significant increase (46%) in cyclical vomiting syndrome–related hospitalizations from 2010 to 2014 (806 vs 1180; P < .001). The overall prevalence of cannabis use in cyclical vomiting syndrome was higher than non–cyclical vomiting syndrome-related hospitalizations (1.7%; P < .001). Colorado approved legalization of cannabis for recreational use in 2012. Subsequently cannabis use increased in both cyclical vomiting syndrome– and non–cyclical vomiting syndrome–related hospitalizations after 2012.
Based on the results of this retrospective review, the authors noted that there was a significant increase in cyclical vomiting syndrome–related hospitalizations related to cannabis use, which reflected an increase in cannabis use throughout the state as a result of legalization of the product within the state in 2012. They suggested that overall monitoring of cyclical vomiting syndrome–related events and hospital admissions may be informative as more states legalize cannabis.
Cannabis [Cannabis]
Bhandari S et al (S Bhandari, Division of General Internal Medicine, Froedtert and the Medical College of Wisconsin, 8701 W Watertown Plank Road, HUB-7th Floor, Milwaukee, WI 53226; e-mail:
OPIOIDS No. 153
Cytochrome P450 Drug-Drug Interactions
A case series including 1000 children undergoing tonsillectomy was performed to determine the frequency with which medications that were known to inhibit or induce the cytochrome P450 (CYP) metabolism of opioid medications were prescribed postoperatively. A total of 157 unique medications with systemic absorption were given to the cohort in the postoperative period. The mean and median numbers of discharge medications were 3 and 3.7 (95% confidence interval = 3.58-3.85), respectively. The most commonly prescribed medications included oxycodone (84%), acetaminophen (75%), ibuprofen (62%), albuterol (24%), cetirizine (12%), hydrocodone (11%), fluticasone nasal (10%), azithromycin (7%), montelukast (6%), and polyethylene glycol (6%). A total of 30 patients (3%) were prescribed a CYP3A4 inhibitor, 1 (<1%) was prescribed a CYP3A4 inducer, and 46 (5%) were prescribed a CYP2D6 inhibitor according to the US Food and Drug Administration’s CYP interactions table.
The authors concluded that in this study, a small number of pediatric patients were prescribed medications that could potentially alter the CYP metabolism of opioids. However, they cautioned that altered opioid metabolism may affect the serum levels of opioids in pediatric patients with obstructive sleep apnea and increase risk of adverse reactions.
Opioids [Opioids]
Faria J et al (J Faria, Pediatric Otolaryngology, University of Rochester, 2365 S Clinton Ave, Suite 200, Rochester, NY 14618; e-mail:
VARENICLINE No. 154
Angioedema
A 64-year-old female patient was hospitalized with shortness of breath due to facial and neck swelling within an hour after taking a second dose of varenicline (0.5 mg). Concurrent medications included acarbose (100 mg 3 times daily), repaglinide (1 mg twice daily), and amlodipine (5 mg once daily). On physical examination, the patient was tachypneic (28 breaths/min), tachycardic (113 beats/min), and hypotensive (101/56 mm Hg). There was significant swelling of the lips, tongue, face, and neck. Abnormal laboratory values indicated respiratory alkalosis and mild hyperglycemia (149 mg/dL). Symptoms continued despite treatment with intramuscular epinephrine (0.5 mg), intravenous diphenhydramine (50 mg), and intravenous methylprednisolone (125 mg). Nasotracheal intubation was required. The patient was transferred to an intensive care setting. The swellings abated over a 2-day period. The patient was successfully extubated on hospital day 4. Varenicline was discontinued. The patient was discharged on hospital day 8 without further event.
The authors concluded that this patient experienced angioedema related to varenicline therapy based on the temporal relationship between the administration of the drug and the appearance and resolution of symptoms.
Varenicline [“Chantix”]
Seak CJ et al (CH Li, Department of Emergency Medicine, Lin-Kou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, and College of Medicine, Chang Gung University, Taoyuan, Taiwan; e-mail:
PALIPERIDONE PALMITATE No. 155
Neuroleptic Malignant Syndrome
A database report including 5008 patients in the Janssen paliperidone palmitate 1-monthly and 3-monthly injections clinical trials database was performed to determine the incidence and nature of neuroleptic malignant syndrome associated with paliperidone palmitate long-acting injections. One credible case of neuroleptic malignant syndrome was identified resulting in a raw incidence of 0.02% (95% confidence interval = 0.0028% to 0.14%) and an incidence rate of 0.044% (95% confidence interval = 0.042% to 0.13%) per year. The case was a 55-year-old man who developed confused mental state, fever (38.8°C), and rigidity on day 15 of the trial after receiving paliperidone palmitate long-acting injection (50 mg on days 1 and 8) for treatment of schizophrenia, paranoid type. No concurrent medications were reported; however, he had previously been treated with flupenthixol decanoate (15 mg intramuscularly every 2 weeks) for 6 years, which was discontinued 22 days prior to randomization. Significant laboratory findings included elevated creatinine kinase (5824 units/L) and hepatic enzymes (aspartate transaminase 128 units/L, alanine transaminase 91 units/L). Treatment included lorazepam (0.5-1 mg/day as needed), ciprofloxacin (500 mg twice daily for 6 days for suspected infection), and discontinuation of paliperidone palmitate with study withdrawal. Laboratory abnormalities improved (creatinine kinase 860 units/L, alanine transaminase 52 units/L, aspartate transaminase 49 units/L) by day 20. Additional treatment included benztropine (1-2 mg/day for 7 days then tapered). Antipsychotic therapy was changed to flupenthixol decanoate (15 mg intramuscularly every 2 weeks), and he was discharged for a leave from the hospital on day 28. Fever recurred on day 34 (temperature 38.5°C). Temperature returned to normal, and all investigations were normal. Discharge occurred on day 46 following a complete recovery.
The authors concluded that this database review revealed a low propensity for neuroleptic malignant syndrome associated with paliperidone palmitate long-acting injections and that one case was found in the clinical trials database. The proposed mechanism was antipsychotic-induced dopamine receptor blockade.
Paliperidone Palmitate [“Invega Sustenna,” “Invega Trinza”]
Kane JM et al (JM Kane, The Zucker Hillside Hospital, Glen Oaks, NY; e-mail:
TATTOO INK No. 156
FDA Safety Communication: Contamination Announcement
On May 15, 2019, the US Food and Drug Administration (FDA) alerted tattoo artists and clients regarding the potential for serious injury and infection associated with the use of tattoo inks that are contaminated with bacteria. Frequently cited symptoms of tattoo ink–associated infections include rashes or lesions (eg, red papules in areas) at the site of application. Some tattoo infections can result in permanent scarring. Several ink brands have already been recalled and can be located on the FDA website in the announcement.
Tattoo Ink [Tattoo Ink]
FDA Safety Communication: FDA advises consumers, tattoo artists, and retailers to avoid using or selling certain tattoo inks contaminated with microorganisms. https://www.fda.gov/cosmetics/cosmetics-recalls-alerts/fda-advises-consumers-tattoo-artists-and-retailers-avoid-using-or-selling-certain-tattoo-inks?utm_campaign=Avoid%20Using%20or%20Selling%20Certain%20Tattoo%20Inks%20Contaminated%20with%20Microorganisms&utm_medium=email&utm_source=Eloqua (May 15) 2019
DULOXETINE No. 157
Acute Renal Injury
A 63-year-old female patient experienced decreased urine output followed by complete cessation of urinary activity after approximately 5 weeks of duloxetine therapy. The drug was initiated at 30 mg daily, and after 1 month was increased to 60 mg daily. Concurrent medications included insulin (20 units daily). Additional symptoms prior to hospitalization included delirium. On admission, a physical examination revealed suprapubic distension and suprapubic tenderness. Abnormal laboratory values included creatinine (6.3 mg/dL) and blood urea nitrogen (72 mg/dL). An abdominal ultrasonographic imaging revealed horseshoe kidney anomaly and excessive distension in the bladder. Urethral catheterization resulted in 6000 mL output. The patient was eventually diagnosed with uremic encephalopathy. Treatment included the discontinuation of duloxetine and the initiation of lorazepam (3 mg daily). On hospital days 2 and 8, the creatinine level decreased to 1.5 mg/dL and 1 mg/dL, respectively. After the removal of the urethral catheter, urinary retention did not recur. By hospital day 6, the patient’s cognition returned to baseline.
The authors concluded that this patient experienced urinary retention and acute renal injury related to duloxetine therapy based on the temporal relationship between the administration of the drug and the appearance and resolution of symptoms.
Duloxetine [“Cymbalta”]
Aktürk Esen S et al (S Aktürk Esen, Department of Internal Medicine, Cüneyt Yıldız State Hospital, Bursa, Turkey; e-mail:
FUSIDIC ACID, STATINS No. 158
Drug Interaction: Muscle Injury
Based on a review of the French national pharmacovigilance database and a comprehensive literature review, 75 cases of muscle damage related to and interaction between fusidic acid and a statin were identified. The majority of identified cases were from the pharmacovigilance database (43 vs 32). The majority of patients were male (72.5%) and overweight (mean body mass index 29.4). The most commonly reported statins were atorvastatin (60%), simvastatin (22.7%), and rosuvastatin (8.0%). The mean onset of muscle disorders after the initiation of fusidic acid was 30.1 days (range = 1-210 days). The most frequently cited symptoms included muscle weakness (81.8%), dark urine (71.4%), and myalgia (60.7%). Acute renal injury occurred in more than half of the cases. Mortality was documented in 22% of the cases. The majority of patients (75.8%) received intravenous hydration; corticosteroids were administered to 3 patients.
Based on the results of this small retrospective review, the authors noted that there can be significant morbidity and mortality associated with the concurrent use of fusidic acid and statins.
Fusidic Acid [Fusidic Acid]
Statins [Atorvastatin, Simvastatin, Rosuvastatin]
Bataillard M et al (M Bataillard, Internal Medicine Department, University Hospital of Saint-Etienne, 42055 Saint-Etienne cedex 2, France; e-mail: