Abstract
Keywords
Dolutegravir No. 1
Colitis
A female patient (age not specified) with chronic HIV infection developed moderate diarrhea with occasional incontinence approximately 3 weeks after being switched from abacavir/lamivudine and efavirenz to abacavir/lamivudine and dolutegravir. Concurrent chronic medications (at least 2 years) included alendronate, cholecalciferol, levothyroxine, loratadine, montelukast, and pravastatin. Screenings for infectious etiologies were negative. After symptoms persisted for an additional 2 weeks, a colonoscopy with biopsy was performed. The colon and terminal ileum appeared normal. Biopsies of the colon demonstrated active inflammation and diffuse, prominent apoptotic crypt epithelial injury. Drug-induced colitis was suspected. Therapy was switched back to efavirenz after the dolutegravir therapy was discontinued. Diarrhea resolved within 2 weeks of stopping the dolutegravir.
The authors concluded that this patient experienced dolutegravir-induced colitis based on the temporal relationship between the administration of the drug and the appearance and resolution of the symptoms. Though an exact mechanism of action was not proposed, the authors noted that most cases of diarrhea identified in clinical trials were mild and self-limiting.
Dolutegravir [“TriumeQ,” “Tivicay”]
Bares SH et al (SH Bares, Department of Internal Medicine/Infectious Diseases, University of Nebraska Medical Center, Omaha, NE; e-mail:
α-Adrenoceptor Blockers No. 2
Hip/Femur Fractures
A retrospective case series study based on claims from the Nationwide Health Insurance program in Taiwan was performed to evaluate the relative risk of hip/femur fractures in 5875 elderly males (aged 50 years and older) during the initiation period of α-adrenoceptor blocker therapy. α-Adrenoceptor blockers included terazosin (n = 1238), doxazosin (n = 1460), tamsulosin (n = 2806), and alfuzosin (n = 371). The mean age was 75.9 (standard deviation = 9.5) years at study onset, 77.2 (standard deviation = 9.5) years at initiation of α-adrenoceptor blocker, and 77.4 (standard deviation = 9.5) years at occurrence of hip/femur fracture. Comorbidities were common and included hypertension (64.1%), diabetes (32.2%), and chronic pulmonary disease (26.1%). Concurrent medications included benzodiazepines (76.0%), corticosteroids (67.5%), bisphosphonates (16.4%), and selective serotonin reuptake inhibitors (10.0%). The incidence rate ratios of hip/femur fractures within the 21 days following initiation of α-adrenoceptors and within 22 to 60 days following initiation were 1.13 (95% confidence interval = 0.95-1.34, P = .07) and 0.87 (95% confidence interval = 0.75-1.01, P = .07), respectively, as compared with the background unexposed period after adjusting for time-varying confounders. The incidence rate ratios of hip/femur fracture for the 21 days immediately prior to exposure and the 22 to 60 days prior to exposure were 3.26 (95% confidence interval = 2.93-3.64, P < .001) and 1.90 (95% confidence interval = 1.70-2.11, P < .001), respectively, as compared with the background unexposed period. The incidence rate ratios of hip/femur fractures were similar among subjects with concomitant antihypertensive use as compared with the whole study population. The incidence rate ratios of hip/femur fractures were also similar among subjects without concomitant antihypertensive therapy as compared with the whole study population; however, a significantly elevated incidence rate ratio (1.36, 95% confidence interval = 1.06-1.74, P = .017) was noted within the 21 days after exposure, but was not significantly different during the 22 to 60 days following exposure. No significant effects were demonstrated with the individual antihypertensive agents evaluated.
The authors concluded that results of this study demonstrated that use of an a-adrenoceptor was associated with a small but significant increase in the risk of hip/femur fracture during early initiation in patients without concomitant prescriptions for antihypertensive agents. Proposed mechanisms included inherent cardiovascular adverse effects including dizziness and hypotension due to effects of a-adrenoceptors on lowering blood pressure.
α-Adrenoceptor Blockers [“Cardura,” “Flomax,” “Hytrin,” “Uroxatral”]
Lai CL et al (MS Lai, Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; e-mail:
Dietary Supplement No. 3
FDA Public Notification: Undeclared Drug Ingredients
On December 23, 2015, the US Food and Drug Administration notified health care professionals and patients regarding undeclared prescription drug ingredients in a dietary supplement promoted for use as weight loss product. The product, La’ Trim Plus, Jenesis, and Oasis, contained sibutramine and phenolphthalein. Sibutramine was a prescription drug marketed in the United States for the treatment of weight loss and removed from the market in October 2010. It was associated with a variety of cardiac adverse events that were related to its market withdrawal. Phenolphthalein was an ingredient found in many nonprescription laxative products. It was subsequently withdrawn due to potential issues with carcinogenicity, gastrointestinal disturbances, and cardiovascular events. The administration of any of these agents without knowledge or consent could cause adverse events. Patients are encouraged to dispose of purchased product and to not purchase in the future. The Food and Drug Administration has also noted that this notification is one in a series of recent events in which dietary supplements and food products have contained undeclared drug products.
Dietary Supplement [“La’ Trim Plus,” “Jenesis,” “Oasis”]
FDA Public Notification: La’ Trim Plus, Jenesis, Oasis by BeeXtreme: Recall—undeclared drug ingredients. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm478890.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Dec 23) 2015
Paliperidone Palmitate No. 4
Manic Symptoms (First Report*)
A 22-year-old female developed elevated mood, inflated self-esteem, and decreased need for sleep the second day after switching antipsychotic therapy from oral paliperidone extended release (9 mg daily) to intramuscular paliperidone palmitate (150 mg once monthly) for the treatment of schizophrenia. No concurrent psychotropic or somatic drugs were ingested. Mental State Exam revealed pressure of speech. Acceleration in thought and flight of ideas were reported. Poor insight and judgement were demonstrated. There was no history of substance abuse, medical or neurological disorders, depression, mania, or hypomanic symptoms. Physical and neurological examinations revealed no new abnormalities. Laboratory analyses including whole blood count, electrolytes, serum ethanol, liver, renal, and thyroid function tests revealed no abnormalities. Electrocardiography and electroencephalography were unremarkable, and magnetic resonance imaging of the brain was normal. Treatment included administration of oral lithium carbonate (600 mg/day titrated to 900 mg/day), and the second dose of paliperidone palmitate (100 mg) was administered on the eighth day. Symptoms declined at the second week following the first paliperidone injection, and within 3 weeks mood had completely stabilized. Lithium was gradually discontinued in the sixth month. Psychotic symptoms continued to be managed with paliperidone palmitate (150 mg per month) without recurrence of manic or hypomanic symptoms.
The authors concluded that this case described the first report of mania related to switching from oral paliperidone to paliperidone palmitate. They further concluded that mania had a probable association with paliperidone palmitate as assessed via the Naranjo causality scale. Proposed mechanisms included D2 and 5-HT2A receptor blockade and α2-antagonist effects induced by paliperidone.
Paliperidone Palmitate [“Invega Sustenna”]
Demirci K et al (K Demirci, Department of Psychiatry, School of Medicine, Sϋleyman Demirel University, 32200 Isparta, Turkey; e-mail:
Insulin No. 5
Distant Site Lipodystrophy
A 60-year-old female patient developed a significant depression in her interscapular region of approximately 3 months duration during insulin therapy over the previous year. The patient had administered premixed human insulin regimen (30% regular and 70% neutral protamine Hagedorn) twice daily (total daily dose of 50 IU) for a year. Concurrent medications included metformin (2 g daily). The patient had been injecting herself in the anterior abdomen using the correct method and also employing regular rotation of the injection site. On physical examination, there was no evidence of lipodystrophy at the injection site. Anti-insulin antibodies were high (>100 U/mL). A punch biopsy of the affected area revealed epidermal atrophy with intradermal chronic lymphocytic infiltration. The patient was diagnosed with insulin-associated distant site lipoatrophy. The insulin injection sites were changed from the anterior abdomen to the anterolateral aspects of both of thighs. Partial reversal of the lipodystrophy occurred after this change.
The authors concluded that this patient experienced a rare event of distant site lipodystrophy related to insulin use despite appropriate administration techniques. According to causality algorithms, the reaction was rated as probable/likely via the World Health Organization-The Uppsala Monitoring Centre causality assessment scale and as probable via the Naranjo probability scale.
Insulin [Insulin]
Chakraborty PP & Biswas SN (PP Chakraborty, Department of Medicine, Midnapore Medical College & Hospital, House No. BE 64, Bidhan Nagar (East), Midnapore 721101, West Bengal, India; e-mail:
Rivaroxaban No. 6
Jaundice, Intrahepatic Cholestasis (First Report*)
A 71-year-old male developed jaundice, severe icterus, and pruritus approximately 1 month after anticoagulation therapy was changed from warfarin to rivaroxaban (15 mg daily) to reduce the risk of stroke and systemic embolism in atrial fibrillation. Concurrent medications included perindopril/indapamide, spironolactone, furosemide, and carvedilol (doses not reported). Electrocardiogram revealed atrial fibrillation. Transthoracic echocardiography determined left ventricular ejection fraction to be 30% and displayed normal valvular function. Laboratory analysis revealed a cholestatic pattern of liver test elevation including alanine aminotransferase (141 units/L), aspartate aminotransferase (152 units/L), γ-glutamyl transferase (259 units/L), alkaline phosphatase (257 units/L), total bilirubin (3.6 mg/dL), conjugated bilirubin (3.6 mg/dL), and elevated serum creatinine (2.2 mg/dL). Hepatobiliary ultrasonography revealed biliary sludge in the gallbladder. Abdominal contrast-enhanced computed tomography revealed edematous but normal choledoch and hydropic gallbladder with minute gallstones and gall bladder sludge. Diffuse jaundice in the sclera and throughout the body was present. All medications were initially continued, and repeat laboratory analysis 8 days later included alanine aminotransferase (39 units/L), aspartate aminotransferase (47 units/L), γ-glutamyl transferase (98 units/L), alkaline phosphatase (295 units/L), total bilirubin (13.2 mg/dL), conjugated bilirubin (11.5 mg/dL), and serum creatinine (1.2 mg/dL). Treatment included discontinuation of rivaroxaban, and anticoagulation therapy was continued with subcutaneous enoxaparin. Rapid biochemical and clinical recovery occurred, and repeat biochemical levels after 2 weeks were improved (alanine aminotransferase 24 units/L, aspartate aminotransferase 28 units/L, γ-glutamyl transferase 36 units/L, alkaline phosphatase 168 units/L, total bilirubin 4.5 mg/dL, conjugated bilirubin 4.3 mg/dL). Long-term anticoagulation was continued with another new-generation anticoagulant (agent not reported) without any further problems. Liver function tests remained normal; however, jaundice did not completely resolve.
The authors concluded that this case described the first report of jaundice due to intrahepatic cholestasis associated with rivaroxaban. The authors stated that the mechanism was unknown but may have involved complex interactions of several rare factors including immune-mediated reactions.
Rivaroxaban [“Xarelto”]
Aslan AN et al (Abdullah AN, Atatϋrk Education and Research Hospital, Department of Cardiology, Ankara 06800, Turkey; e-mail:
Dietary Supplement No. 7
FDA Public Notification: Undeclared Drug Ingredients
On December 18, 2015, the US Food and Drug Administration notified health care professionals and patients regarding undeclared prescription drug ingredient in a dietary supplement promoted for use as a sexual enhancement. The product, X Again Platinum, contained sildenafil, tadafil, and dapoxetine. The first 2 ingredients are prescription drugs marketed in the United States for the treatment of erectile dysfunction. Both agents can cause significant hypotension and have been known to cause severe drug interactions when taken concurrently with nitrates. The latter agent is a drug product not approved in the United States and thus does not have a safety record established in this country. The administration of any of these agents without knowledge or consent could cause adverse events. Patients are encouraged to dispose of purchased product and to not purchase in the future. The Food and Drug Administration has noted that this notification is one in a series of recent events in which dietary supplements and food products have contained undeclared drug products.
Dietary Supplement [“X Again Platinum”]
FDA Public Notification: X Again Platinum contains hidden drug ingredients. http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/MedicationHealthFraud/ucm478226.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Dec 18) 2015
Baclofen No. 8
FDA Public Notification: Contamination of Product
On December 9, 2015, the US Food and Drug Administration alerted health care professionals and drug compounders that certain lots of baclofen manufactured by Taizhou Xinyou Pharmaceutical & Chemical Co., Limited (Taizhou) Taizhou City, Zhejiang Province, China, may be at risk for contamination with particulates and should not be used to compound sterile injectable drugs. This company is responsible for providing active ingredients for a variety of pharmaceutical manufacturers that manufacture and distribute injectable baclofen, although the specific pharmaceutical companies were not identified. According to the Food and Drug Administration report, the company confirmed that baclofen that it manufactures is not suitable for use in injectable drugs. Based on this information, the Food and Drug Administration recommends that no baclofen from Taizhou be used to manufacture or compound any injectable drugs as this base product poses a potentially serious safety risk for patients who use or receive injectable drugs compounded with the affected baclofen. The Food and Drug Administration report also noted that there may be an additional potential risk that this baclofen product may be contaminated by endotoxin or microorganisms. The Food and Drug Administration announced that this situation will be continually monitored and further investigated.
Baclofen [Baclofen]
FDA Drug Safety Alert: FDA warns of potential contamination of baclofen active pharmaceutical ingredient from Taizhou Xinyou Pharmaceutical & Chemical Co., Limited, China. http://www.fda.gov/Drugs/DrugSafety/ucm476508.htm (Dec 9) 2015
Aflibercept No. 9
Risk of Severe Infections in Cancer Patients
In a meta-analysis, 261 clinical trials evaluating aflibercept in the treatment of cancer were screened for inclusion. Of these, 10 prospective trials enrolling a total of 4310 patients were eligible for inclusion. Four of the studies were phase III trials, and 6 were phase II prospective studies. A total of 2001 patients from 9 studies were included in the analysis for high-grade infections. The incidence in these trials ranged from 1% to 20.1%. Using a random effects model, a pooled incidence of 7.3% (95% confidence interval = 4.3% to 12.0%) for high-grade infections was identified. A significant degree of heterogeneity was identified (I2 = 87%; P < .001). The incidence of fatal infections ranged between 0% and 6.7% with the calculated summary incidence of fatal infections being 2.2% (95% confidence interval = 1.5% to 3.1%). The relative risk of developing a high-grade infection in cancer patients with aflibercept use was 1.87 (95% confidence interval = 1.52 to 2.30; P < .001). The odds ratio of developing a fatal infection in cancer patients with aflibercept use was 2.16 (95% confidence interval = 1.14 to 4.11; P = .018). There was no evidence of publication bias. The risk of infections was compared with aflibercept and bevacizumab, another anti-angiogenesis agent. A meta-analysis with bevacizumab was conducted recently. When data from this meta-analysis were used, the risk of developing all grade and high-grade infections was significantly higher with aflibercept when compared to bevacizumab having a relative risk of 4.07 (95% confidence interval = 3.68 to 4.51; P < .001) and 2.68 (95% confidence interval = 2.34 to 3.08; P < .001), respectively.
Based on this meta-analysis, the authors concluded that aflibercept is associated with a significant increased risk of developing severe infections in cancer patients. They suggested that frequent clinical monitoring and management of infections is warranted during therapy with this agent.
Aflibercept [“Eylea”]
Zhang X et al (X Zhang, Department of Radiation Oncology, Affiliated Hospital of Hebei University, 212 East Yuhua Road, Baoding, 071000 Hebei, People’s Republic of China; e-mail:
Moxifloxacin No. 10
Delirium
A 78-year-old male patient became confused after 3 days of treatment with oral moxifloxacin (400 mg daily) and acetaminophen for the treatment of a respiratory infection. Symptoms of the confused state included attention alteration, disorientation to space and time, recent memory difficulties, stiff upper limb with resting tremor, and gait disturbance. Laboratory values were within normal limits. A computed tomography of the head was unremarkable with the exception of a marked ventricular dilation out of proportion to cortical atrophy. By the fifth day of treatment, there were no symptoms of the respiratory infection and the patient was alert. However, he still remained disoriented to place and time. In addition, the symptoms of recent memory impairment and the upper limb stiffness persisted. Mild cognitive impairment was apparent via assessment. The patient was diagnosed with acute delirium according to the Diagnostic and Statistical Manual of Mental Disorders, possibly related to moxifloxacin. The drug was discontinued with gradual recovery of cognitive and functional status to that of baseline levels prior to antibiotic therapy.
The authors concluded that this patient experienced moxifloxacin-associated delirium based on the temporal relationship between the administration of the drug and the appearance and resolution of symptoms. According to the Naranjo causality algorithm, the reaction was rated as probable in relation to the drug therapy. The authors noted that contributing factors many have included advanced age, fever, and cortical atrophy.
Moxifloxacin [“Avelox”]
Pozo ED et al (ED Pozo, Department of Pharmacology, Faculty of Medicine, University of Granada, Granada, Spain) Acute confusional syndrome induced by moxifloxacin in an elderly man. J Am Geriatr Soc 63:2647–2648 (Dec) 2015
Rivastigmine (Transdermal) No. 11
Bradycardia
An 83-year-old male inpatient was noted to have sinus bradycardia (46 bpm) with a PR interval of 0.24 seconds and an incomplete right bundle branch block on hospitalization. Medications on admission included escitalopram (10 mg daily), tamsulosin (0.4 mg daily), trazodone (50 mg daily), and rivastigmine (18 mg patch). On physical examination, it was noted that there was rigidity in the right upper extremity. Laboratory values were within normal limits. Based on the suspicion that rivastigmine use may be associated with the bradycardia, the drug was discontinued. The bradyarrhythmia resolved the next day (heart rate 68 bpm). When the drug was restarted, the bradycardia recurred, establishing a positive rechallenge relationship. Other signs and symptoms of cardiac events were absent. Reevaluation at 10 days after discharge revealed that the heart rate was within normal limits. No further events were noted.
The authors concluded that this patient experienced rivastigmine-related bradycardia based on the temporal relationship between the drug administration and the appearance and resolution of the symptoms. According to the Naranjo causality algorithm, the reaction was rated as definite in relation to the drug therapy.
Rivastigmine [“Exelon”]
Soysal P & Isik AT (P Soysal, Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey) Asymptomatic bradycardia due to rivastigmine in an elderly adult with Lewy body dementia. J Am Geriatr Soc 63:2648–2650 (Dec) 2015
Memantine No. 12
Myoclonus
A 93-year-old male patient was hospitalized with confusion and worsening of bilateral myoclonus in all limbs. The confusion had started the day prior to admission but the myoclonus began approximately 2 months after starting memantine (10 mg twice daily) and about 4 months prior to admission. Concurrent medications included dextromethorphan, levofloxacin, and chlorpheniramine for an upper respiratory tract infection. Additional symptoms included visual hallucinations, fluctuating attention, and rapid eye movement sleep behavioral disorder. Laboratory screenings indicated an Escherichia coli urinary tract infection and acute renal impairment. Treatment included the discontinuation of memantine and the initiation of low-dose clonazepam. Myoclonus resolved within 2 days after the discontinuation of memantine and did not recur after clonazepam was tapered and stopped.
The authors concluded that this patient experienced memantine-related myoclonus based on the temporal relationship between the drug administration and the appearance and resolution of the symptoms. According to the Naranjo causality algorithm, the reaction was rated as probable in relation to the drug therapy. The authors also suggested that concurrent administration of dextromethorphan and chlorpheniramine may have been contributing factors. As memantine is also primarily cleared by renal excretion, this was considered an additional possible factor in the development of the adverse event.
Memantine [“Namenda”]
Pei LJ et al (LJ Pei, Department of Geriatric Medicine, Tan Tock Seng Hospital, Singapore) Memantine-induced myoclonus precipitated by renal impairment and drug interactions. J Am Geriatr Soc 63:2643–2645 (Dec) 2015
Levetiracetam No. 13
Psoriasiform Eruption
A 35-year-old female patient developed erythematous skin lesions approximately 10 days after the initiation of levetiracetam (500 mg daily) for the treatment of epilepsy. The dose had been gradually increased to 1000 mg daily. There were no concurrent medications noted in the report. There was no personal or family history of psoriasis. A physical examination revealed erythematous plaques with scales on both knees and elbows. There was no involvement of the scalp, nails, and palmar plantar regions. All laboratory values were within normal limits with the exception of high eosinophils. A skin biopsy revealed irregular acanthosis of epidermis, edema in papillary dermis, and perivascular infiltration. The diagnosis was psoriasiform drug eruption related to levetiracetam. Management included the discontinuation of the drug and the initiation of carbamazepine (400 mg daily). Skin eruptions gradually resolved within a few weeks after the drug was discontinued. No further dermal events were noted during follow-up evaluation.
Levetiracetam [“Keppra”]
Gencler OS et al (OS Gencler, Department of Neurology, Faculty of Medicine, Turgut Ozal University, Ankara, Turkey; e-mail address:
Acenocoumarol, Levofloxacin No. 14
Drug Interaction
A potential drug interaction between acenocoumarol and levofloxacin is described in a case series of 5 patients who had been stabilized on at least 6 months of acenocoumarol treatment prior to the initiation of levofloxacin. Significant elevations in the international normalized ratios were observed after 1.5 to 8 days of concurrent acenocoumarol and levofloxacin therapy.
Patient 1. A 90-year-old male patient previously stabilized on acenocoumarol was initiated on oral levofloxacin therapy (500 mg daily) for the treatment of a respiratory infection. On initial evaluation, relevant laboratory screenings included serum creatinine (1.28 mg/dL), urea (84 mg/dL), creatinine clearance (49 mL/min), and international normalized ratio (2.19). After 8 days of concurrent therapy, the patient was reevaluated with significant increases noted in serum creatinine (2.39 mg/dL), urea (256 mg/dL), and international normalized ratio (9.42). Management included the discontinuation of acenocoumarol, the initiation of oral vitamin K (5 mg), and substitution with subcutaneous enoxaparin. The international normalized ratio eventually returned to therapeutic range.
Patient 2. An 81-year-old female inpatient with pneumonia was taking acenocoumarol when hospitalized. Relevant laboratory screenings on admission included international normalized ratio (7.75), serum creatinine (1.3 mg/dL), creatinine clearance (32 mL/min), and urea (93 mg/dL). Intravenous levofloxacin (500 mg every 24 hours) was initiated. Within 2 days, a repeat international normalized ratio was noted at 22, requiring 3 doses of intravenous vitamin K (10 mg twice daily). Acenocoumarol was discontinued and subcutaneous enoxaparin (40 mg) was substituted. Within 2 days, the international normalized ratio returned to a therapeutic level (1.42). The patient died due to cardiovascular complications.
Patient 3. A 93-year-old male patient stabilized on acenocoumarol was hospitalized with laboratory values including serum creatinine (1.58 mg/dL), creatinine clearance (29 mL/min), and an international normalized ratio (1.72). On hospital day 5, levofloxacin (500 mg once daily) was initiated as intravenous dosing for the first 2 days followed by oral dosing. After 8 days of concurrent therapy, the international normalized ratio value increased to 7.05 with worsening renal function. Management included the discontinuation of acenocoumarol, the administration of intravenous vitamin K (10 mg), and the reduction of the levofloxacin dose (250 mg daily). The international normalized ratio eventually was reduced within therapeutic range.
Patient 4. An 87-year-old male patient stabilized on acenocoumarol was hospitalized with a respiratory infection. On admission, relevant laboratory values included international normalized ratio (2.83), serum creatinine (1.55 mg/dL), and urea values (50 mg/dL). Levofloxacin (500 mg every 12 hours) was initiated. On day 4 of therapy, the dose was reduced to 500 mg once daily. An increased international normalized ratio of 14.53 was noted. Management included the administration of intravenous vitamin K (10 mg) and holding a dose of acenocoumarol. The international normalized ratio decreased to 1.6 by the next day. Levofloxacin was discontinued.
Patient 5. A 92-year-old male patient stabilized on acenocoumarol prior to admission was hospitalized with pneumonia. On admission, relevant laboratory values included serum creatinine (0.83 mg/dL), urea (45 mg/dL), and creatinine clearance (56 mg/min). After 2 days of concurrent therapy with intravenous levofloxacin (500 mg daily), the international normalized ratio was elevated (2.82). Management included the discontinuation of acenocoumarol and the substitution of amoxicillin/clavulanic acid. On hospital day 3, the patient was discharged on oral levofloxacin (500 mg daily for 7 days) and steroids. After 6 days of concurrent therapy the patient was readmitted with dysarthria and disorientation. Relevant laboratory screenings on this admission included serum creatinine (0.86 mg/dL), creatinine clearance (54 mL/min), urea (54 mg/dL), and international normalized ratio (6.78). Management included the administration of intravenous vitamin K (10 mg). The next day, the international normalized ratio was within therapeutic range.
The authors noted that these patients most likely experienced elevated international normalized ratios due to a drug interaction between acenocoumarol and levofloxacin. Although an exact mechanism of action is not clear, the authors recommended that international normalized ratios be monitored closely during concurrent therapy with these agents.
Acenocoumarol [“Acenocoumarol”]
Levofloxacin [“Levaquin”]
Palacios-Zabalza I et al (I Palacios-Zabalza, Hospital Pharmacist, Department of Pharmacy, Galdakao-Usansolo Hospital, 48960 Galdakao, Bizkaia, Spain; e-mail: