Relative Safety Profile Research Articles

A normal life expectancy, despite HIV infection?

A normal life expectancy, despite HIV infection?

Comparison of liposomal doxorubicin versus conventional anthracyclines: A meta-analysis.

e13128 Background: Liposomal formulations of anthracyclines have similar efficacies and favorable toxicity profile when compared with conventional anthracyclines in elderly, high-risk cardiac patients and prior patients with prior use of anthracylines. In this study, we performed a meta-analysis to evaluate the adverse effects and quantify the relative safety profile of the liposomal and conventional anthracyclines. Methods: We conducted a broad search strategy of major electronic databases. We performed a meta-analysis of adverse effects on randomized controlled trials comparing liposomal formulation and conventional anthracyclines on different tumors. The primary outcome was the adverse effects including CHF, hematologic toxicity, Palmar-plantar erythrodysthesias, alopecia, nausea, and vomiting. The odds ratios of the adverse effects were calculated separately and the overall odds ratio of the pooled data was calculated. We use the fixed effect model for the meta-analysis and compared it with the random effect model. Results: We identified nine randomized controlled trials comparing liposomal formulations and conventional anthracyclines. The study included 2,220 patients of which 1,112 patients were treated with liposomal formulations and 1,108 were treated with conventional anthracyclines. We found that the liposomal formulations have low incidence of CHF (OR 0.34, 95% CI, 0.24-0.47), alopecia (OR 0.36, 95% CI, 0.29-0.43), neutropenia (OR 0.65, 95% CI, 0.53-0.80), neutropenic fever (OR 0.90, 95% CI, 0.68-1.20), anemia (OR 0.89, 95% CI, 0.71-1.125), thrombocytopenia (OR 0.87, 95% CI, 0.61-1.25) and higher incidence of palmar-plantar erythrodysthesias (OR 3.14, 95% CI, 2.30-4.29). Conclusions: Liposomal doxorubicin and pegylated liposomal doxorubicin demonstrated favorable toxicity profiles with better cardiac safety and less myelosuppression, alopecia, nausea, and vomiting compared with the conventional antracyclines. No significant financial relationships to disclose.

The Dublin Consensus Statement on vital issues relating to the collection of blood and plasma and the manufacture of plasma products

The requirement for plasma products manufactured from both source and recovered plasma for the treatment of many medical conditions is projected to increase substantially in the course of the next 5 years [1]. Patient organizations representing many thousands of patients with rare disorders who are dependant on products manufactured from plasma formed a coalition of plasma usersPLUSin 2009. PLUS represents the concerted views of seven organisations, the International Patients Organisation for Primary Immunodeficiency (IPOPI), the World Federation of Hemophilia (WFH), the European Haemophilia Consortium (EHC), Alfa Europe, Idiopathic Thrombocytopenic Purpura Support Organisation (ITP), Hereditary Angiodema International (HAEI) and Guillain Barre Syndrome Foundation International (GBS ⁄CIDP). Over the last thirty years, the manufacture from plasma of an increasing range of stable clinical products and the availability of plasmapheresis collection technology has led to the development of a commercial industry based on plasma-only donations from remunerated donors. In countries that do not permit a remunerated donor system, plasma collections are limited to those collected by blood establishments operating with nonremunerated donors. The growing global requirement for safe and effective plasma products [1] to meet the health needs of patients mean that plasma from both the commercial plasma and the blood sectors are essential to provide the range and quantity of plasma products required. IPOPI estimate that < 15% of persons with primary immune deficiency worldwide are diagnosed and treated [2]. In 2007, there was a total of 26AE5 million litres of plasma available for fractionation including 8AE6 million litres of recovered plasma and 17AE9 million litres of source plasma [1]. It is estimated that the global requirement for plasma for fractionation by 2015 may be 41AE7 million litres even in the absence of any new indications for IVIG [1]. Patients who are dependant on these life-saving therapies want to be reassured that they will have access to a sufficient supply of safe and effective therapy manufactured from the plasma of carefully selected and tested donors in the future. National policies in most cases only permit a non – remunerated system of blood and plasma collection. This means that commercial plasma collections are limited to a few countries which allow both remunerated and nonremunerated donations including the United States of America, Germany, Czech Republic and Austria. Most countries utilize domestic nonremunerated blood collection to fully satisfy their requirements for labile blood components. However, the vast majority of these countries also import additional products from the commercial plasma sector to fully meet their health needs. The plasma fractionation sector comprises both commercial and not for profit manufacturers, and these compete in both global and national markets. Where both commercial and not for profit plasma collection or manufacturing systems coexist or compete at a national level, there can be tensions and disagreements between the sectors on issues such as the relative safety profile of remunerated and nonremunerated donors, as well as competition for donors. Correspondence: Brian O. Mahony, Cheif Executive, Irish Haemophilia Society, Steering Group PLUS, Cathedral Court, New Street South, Dublin 8, Ireland E-mail: brian@haemophilia.ie Vox Sanguinis (2010)

Ultrasound-guided Subcostal Transversus Abdominis Plane Block

Ultrasound-guided subcostal transversus abdominis plane block is a recently described regional anaesthetic technique for providing postoperative analgesia after upper abdominal surgery. Use of subcostal TAP catheters holds considerable promise on account of its relative simplicity, efficacy and safety profile. This article reviews the current literature on this technique and reflects on personal experience.

Rationale, design, and governance of Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION), a cardiovascular end point trial of nonsteroidal antiinflammatory agents in patients with arthritis

Pain management in patients with osteoarthritis or rheumatoid arthritis often requires long-term use of nonsteroidal antiinflammatory drugs (NSAIDs). However, the relative cardiovascular safety of these therapies remains uncertain. The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION) trial will evaluate the cardiovascular safety of celecoxib, ibuprofen, and naproxen. Approximately 20,000 patients with symptomatic osteoarthritis or rheumatoid arthritis at high risk for, or with, established cardiovascular disease will be randomized in this double-blind, triple dummy, multinational, multicenter study. The primary end point is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial will continue until 762 primary events occur with at least 18 months follow-up. Noninferiority of any of the regimens will require a 97.5% upper CI of the hazard ratio (HR) < or =1.33 and point estimate < or =1.12 for both intent-to-treat (ITT) and modified ITT populations. PRECISION, the first study of patients with high cardiovascular risk chronically treated with a cyclooxygenase-2 selective inhibitor or nonselective NSAID, will define the relative cardiovascular safety profile of celecoxib, ibuprofen, and naproxen and provide data to help guide NSAID use for pain management for this population.

Randomized phase II trial of first-line gefitinib, gemcitabine or docetaxel in performance status (PS) 2 or 3 non-small cell lung cancer (NSCLC) patients (IFCT-0301): elderly patients analysis

Many patients with head and neck cancer have difficulty swallowing tablet formulations ofmedications, and use of dispersion preparations may be advantageous.The aim of the present study was to determine the relative bioavailability and safety profile of asingle dose of gefitinib, an orally active inhibitor of epidermal growth factor receptor tyrosine kinase, when administered as a whole 250-mg tablet or as a dispersion preparation via drink or nasogastric tube in healthy male volunteers.This was a Phase 1, randomized, open-label, 3-period crossover study. Plasma samples obtained beforedosing to 240 hours after dosing were analyzed for gefitinib using reverse-phase high-performance liquid chromatography with tandem mass-spectrometric detection. The pharmacokinetic parameters of interest included AUC, Cmax, and the relative bioavailability of the dispersion via drink or nasogastric tube compared with the standard tablet.Eighteen healthy white male volunteers were enrolled. They had a mean age of 43 years (range, 21–59 years), mean body weight of 85.1 kg (range, 60–101 kg), and mean height of 180.3 cm (range, 171–187 cm). The geometric mean AUC was 2219 ng·h/mL for a single 250-mg dose of gefitinib administered as a whole tablet, 2233 ng·h/mL for the dispersion preparation administered by drink, and 2007 ng·h/mL for the dispersion preparation administered by nasogastric tube. The corresponding values for the geometric mean Cmax were 95.2, 96.3, and 89.9 ng/mL. The gefitinib dispersion preparation administered by drink had a mean bioavailability of 103.8% relative to the whole tablet; the dispersion preparation administered by nasogastric tube had a mean bioavailability of 99.1% relative to the whole tablet. For the drink-tablet and nasogastric tube-tablet comparisons, the estimate-of-treatment ratios for the AUC were a respective 1.006 and 0.928; for the Cmax, they were 1.012 and 0.964. There appeared to be no clinically significant differences in absorption or elimination between the preparations. Three volunteers experienced adverse events (AEs) that were considered possibly related to gefitinib (pruritus and dry skin), and 6 volunteers experienced procedure-related AEs (cannula-site reaction and rhinorrhea); these AEs were mild or moderate. No serious AEs were recorded, and no AEs led to withdrawal of any volunteer.Administration of a 250-mg dose of gefitinib as a dispersion preparation by drink or nasogastrictube achieved a systemic exposure to gefitinib that was consistent with that achieved when gefitinib was administered as a whole tablet. There was no evidence of tolerability problems associated with the routes of administration studied in these healthy volunteers.

Management of chronic pain in the elderly: focus on transdermal buprenorphine

Chronic pain in the elderly is a significant problem. Pharmacokinetic and metabolic changes associated with increased age makes the elderly vulnerable to side effects and overdosing associated with analgesic agents. Therefore the management of chronic cancer pain and chronic nonmalignant pain in this growing population is an ongoing challenge. New routes of administration have opened up new treatment options to meet this challenge. The transdermal buprenorphine matrix allows for slow release of buprenorphine and damage does not produce dose dumping. In addition the long-acting analgesic property and relative safety profile makes it a suitable choice for the treatment of chronic pain in the elderly. Its safe use in the presence of renal failure makes it an attractive choice for older individuals. Recent scientific studies have shown no evidence of a ceiling dose of analgesia in man but only a ceiling effect for respiratory depression, increasing its safety profile. It appears that transdermal buprenorphine can be used in clinical practice safely and efficaciously for treating chronic pain in the elderly.

Relative safety profiles of high dose statin regimens.

Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.

Documentation of the relative efficacy and safety profile of the salbutamol delivery by slow infusion(SI) VS inhalation(IN) to patients with acute severe bronchial asthma

Documentation of the relative efficacy and safety profile of the salbutamol delivery by slow infusion(SI) VS inhalation(IN) to patients with acute severe bronchial asthma

Con: Aprotinin Has a Good Efficacy and Safety Profile Relative to Other Alternatives for Prevention of Bleeding in Cardiac Surgery

Con: Aprotinin Has a Good Efficacy and Safety Profile Relative to Other Alternatives for Prevention of Bleeding in Cardiac Surgery

The relative efficacy & safety profile of intravenous immunoglobulins (IVIg) in refractory dermatomyositis (RDM)

RATIONALE: (RDM) a clinical condition with an unknown etiology, characterized by the skin rash(Erythema & edema) and complement-mediated microangiopathy resulting in destruction of muscle fibers,when resistant to treatment could terminate in severe physical disabilities.

Efficacy and Tolerability of Ziprasidone Versus Risperidone in Patients With Acute Exacerbation of Schizophrenia or Schizoaffective Disorder

More head-to-head comparisons of antipsychotics are needed to discern the relative efficacy and safety profiles of these compounds. Thus, we compared ziprasidone and risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder. Patients with DSM-III-R acute exacerbation of schizophrenia or schizoaffective disorder were randomly assigned to double-blind ziprasidone 40 to 80 mg b.i.d. (N = 149) or risperidone 3 to 5 mg b.i.d (N = 147) for 8 weeks. Primary efficacy measures included Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions-Severity of Illness scale (CGI-S) score; secondary measures included scores on the PANSS negative sub-scale, CGI-Improvement scale (CGI-I), and PANSS-derived Brief Psychiatric Rating Scale (BPRSd) total and core items. Safety assessments included movement disorder evaluations, laboratory tests, electrocardiography, vital signs, and body weight. Efficacy analyses employed a prospectively defined Evaluable Patients cohort. Treatment equivalence was conferred if the lower limit of the 95% confidence interval of the ziprasidone/risperidone ratio of least-squares mean change from baseline was > 0.60. Data were gathered from August 1995 to January 1997. Equivalence was demonstrated in PANSS total scores, CGI-S scores, PANSS negative subscale scores, BPRSd total and core item scores, and PANSS total and CGI-I responder rates. Both agents were well tolerated. Risperidone exhibited a significantly higher Movement Disorder Burden (MDB) score (p < .05) and higher incidences of prolactin elevation and clinically relevant weight gain. However, compared with current recommendations, study dosing may have been high for some risperidone-treated patients (mean dose = 7.4 mg/day) and low for some ziprasidone-treated patients (mean dose = 114.2 mg/day). Both agents equally improved psychotic symptoms, and both were generally well tolerated, with ziprasidone demonstrating a lower MDB score and less effect on prolactin and weight than risperidone.

Relative bioavailability and safety profile of gefitinib administered as a tablet or as a dispersion preparation via drink or nasogastric tube: results of a randomized, open-label, three-period crossover study in healthy volunteers

Background: Many patients with head and neck cancer have difficulty swallowing tablet formulations ofmedications, and use of dispersion preparations may be advantageous. Objective: The aim of the present study was to determine the relative bioavailability and safety profile of asingle dose of gefitinib, an orally active inhibitor of epidermal growth factor receptor tyrosine kinase, when administered as a whole 250-mg tablet or as a dispersion preparation via drink or nasogastric tube in healthy male volunteers. Methods This was a Phase 1, randomized, open-label, 3-period crossover study. Plasma samples obtained beforedosing to 240 hours after dosing were analyzed for gefitinib using reverse-phase high-performance liquid chromatography with tandem mass-spectrometric detection. The pharmacokinetic parameters of interest included AUC, C max, and the relative bioavailability of the dispersion via drink or nasogastric tube compared with the standard tablet. Results: Eighteen healthy white male volunteers were enrolled. They had a mean age of 43 years (range, 21–59 years), mean body weight of 85.1 kg (range, 60–101 kg), and mean height of 180.3 cm (range, 171–187 cm). The geometric mean AUC was 2219 ng·h/mL for a single 250-mg dose of gefitinib administered as a whole tablet, 2233 ng·h/mL for the dispersion preparation administered by drink, and 2007 ng·h/mL for the dispersion preparation administered by nasogastric tube. The corresponding values for the geometric mean C max were 95.2, 96.3, and 89.9 ng/mL. The gefitinib dispersion preparation administered by drink had a mean bioavailability of 103.8% relative to the whole tablet; the dispersion preparation administered by nasogastric tube had a mean bioavailability of 99.1% relative to the whole tablet. For the drink-tablet and nasogastric tube-tablet comparisons, the estimate-of-treatment ratios for the AUC were a respective 1.006 and 0.928; for the C max, they were 1.012 and 0.964. There appeared to be no clinically significant differences in absorption or elimination between the preparations. Three volunteers experienced adverse events (AEs) that were considered possibly related to gefitinib (pruritus and dry skin), and 6 volunteers experienced procedure-related AEs (cannula-site reaction and rhinorrhea); these AEs were mild or moderate. No serious AEs were recorded, and no AEs led to withdrawal of any volunteer. Conclusions: Administration of a 250-mg dose of gefitinib as a dispersion preparation by drink or nasogastrictube achieved a systemic exposure to gefitinib that was consistent with that achieved when gefitinib was administered as a whole tablet. There was no evidence of tolerability problems associated with the routes of administration studied in these healthy volunteers.

199-ASSOCIATION OF PSYCHODIAGNOSTIC PARAMETERS WITH PAIN PERCEPTION OF INTRACARDIAC SHOCK DISCHARGES—AN ANALYSIS OF 77 PATIENTS WITH AN IMPLANTED CARDIOVERTER DEFIBRILLATOR

Pain management in patients with osteoarthritis or rheumatoid arthritis often requires long-term use of nonsteroidal antiinflammatory drugs (NSAIDs). However, the relative cardiovascular safety of these therapies remains uncertain.The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION) trial will evaluate the cardiovascular safety of celecoxib, ibuprofen, and naproxen. Approximately 20,000 patients with symptomatic osteoarthritis or rheumatoid arthritis at high risk for, or with, established cardiovascular disease will be randomized in this double-blind, triple dummy, multinational, multicenter study. The primary end point is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial will continue until 762 primary events occur with at least 18 months follow-up. Noninferiority of any of the regimens will require a 97.5% upper CI of the hazard ratio (HR) ≤1.33 and point estimate ≤1.12 for both intent-to-treat (ITT) and modified ITT populations.PRECISION, the first study of patients with high cardiovascular risk chronically treated with a cyclooxygenase-2 selective inhibitor or nonselective NSAID, will define the relative cardiovascular safety profile of celecoxib, ibuprofen, and naproxen and provide data to help guide NSAID use for pain management for this population.

Amphotericin B and fluconazole, a potent combination therapy for cryptococcal meningitis.

We evaluated the antifungal activities of amphotericin B, fluconazole, and flucytosine, alone and in combination, in a murine model of cryptococcal meningitis. The objectives were to determine the greatest antifungal effects achievable with these drugs alone or in combination. Meningitis was established in male BALB/c mice weighing 23 to 25 g by intracerebral injection of Cryptococcus neoformans. Treatment was started on day 2. Amphotericin B was tested at 0.3 to 1.3 mg/kg of body weight/day by slow intravenous injection. Fluconazole at 10 to 40 mg/kg/day and flucytosine at 20 to 105 mg/kg/day were administered in the sole source of drinking water. The mice were killed at 16 days, and the numbers of fungal colonies in the brain were quantified. The association between the response and the dose combination was evaluated by local nonparametric response surface methods; 99% confidence intervals were used to evaluate the antifungal effects. Ninety-five percent of the mice treated with amphotericin B at 0.5 mg/kg survived to the end of the experiment, regardless of the fluconazole or flucytosine dose used. The greatest activity was seen with amphotericin B plus fluconazole with or without flucytosine. However, the addition of flucytosine did not increase the antifungal activity. Given the widespread availability of amphotericin B and fluconazole and the relative safety profile of fluconazole compared to that of flucytosine, the full potential of this two-drug combination deserves further evaluation.

Safety in iron management

Intravenous (IV) iron therapy has become an integral part of hemodialysis management during the past several decades, and the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative guidelines recognize that most patients undergoing hemodialysis will require IV iron therapy on a regular basis to reach target hemoglobin (Hgb) levels. There now are three IV iron compounds available in the United States: iron dextran, sodium ferric gluconate, and iron sucrose. Although all have been proven effective for increasing Hgb/hematocrit levels, recent data show differences in their relative safety profiles. During the past two decades, more than 30 deaths have been attributed to the use of IV iron dextran. The two newer compounds available in the United States, sodium ferric gluconate and iron sucrose, have more favorable safety profiles, with the largest prospective safety comparison to date showing sodium ferric gluconate to be similar to placebo in the incidence of serious anaphylactoid-type reactions. This article reviews safety data surrounding the IV iron therapies.

Anti-Inflammatory Effect and Low Ulcerogenic Activity of Etodolac, a Cyclooxygenase-2 Selective Non-Steroidal Anti-Inflammatory Drug, on Adjuvant-Induced Arthritis in Rats

Adjuvant arthritic rats are known to be more susceptible to gastric damage induced by non-steroidal anti-inflammatory drugs (NSAIDs) than are normal rats. We compared the relative gastric safety profile of etodolac with those of meloxicam, diclofenac sodium and indometacin in adjuvant arthritic rats and normal rats or mice. As a measure of the safety profiles of NSAIDs, we used the safety index, the ratio of the dose that elicits gastric mucosal lesions to the effective dose as an anti-inflammatory or analgesic compound. The anti-inflammatory or analgesic effects of NSAIDs were assessed by paw swelling in adjuvant arthritic rats, and either carrageenin-induced paw edema or brewer’s yeast-induced hyperalgesia, as well as acetic acid-induced writhing, in normal rats or mice. In addition, we also investigated the effects of these NSAIDs on human COX-1 and COX-2 activity. Etodolac and other NSAIDs inhibited paw swelling and caused gastric mucosal lesions in adjuvant arthritic rats in a dose-dependent manner. Etodolac showed the highest UD₅₀ value and safety index among these NSAIDs in arthritic rats. In normal rats, etodolac also showed the highest UD₅₀ value and safety index, except when its effects were assessed by acetic acid-induced writhing. Etodolac and meloxicam showed selectivity for human COX-2 over COX-1. In contrast, diclofenac sodium and indometacin were selective for COX-1. These results suggest that etodolac, a COX-2 selective NSAID, has anti-inflammatory effects with a better safety profile for the stomach than do non-selective NSAIDs, including diclofenac sodium and indometacin, in adjuvant arthritic as well as normal rats.

Human Neural Precursor Cells Express Low Levels of Telomerase in Vitro and Show Diminishing Cell Proliferation with Extensive Axonal Outgrowth following Transplantation

Worldwideattention is presently focused on proliferating populations of neural precursor cells as an in vitro source of tissue for neural transplantation and brain repair. However, successful neuroreconstruction is contingent upon their capacity to integrate within the host CNS and the absence of tumorigenesis. Here we show that human neural precursor cells express very low levels of telomerase at early passages (less than 20 population doublings), but that this decreases to undetectable levels at later passages. In contrast, rodent neural precursors express high levels of telomerase at both early and late passages. The human neural precursors also have telomeres (approximately 12 kbp) significantly shorter than those of their rodent counterparts (approximately 40 kbp). Human neural precursors were then expanded 100-fold prior to intrastriatal transplantation in a rodent model of Parkinson's disease. To establish the effects of implanted cell number on survival and integration, precursors were transplanted at either 200,000, 1 million, or 2 million cells per animal. Interestingly, the smaller transplants were more likely to extend neuronal fibers and less likely to provoke immune rejection than the largest transplants in this xenograft model. Cellular proliferation continued immediately post-transplantation, but by 20 weeks there were virtually no dividing cells within any of the grafts. In contrast, fiber outgrowth increased gradually over time and often occupied the entire striatum at 20 weeks postgrafting. Transient expression of tyrosine hydroxylase-positive cells within the grafts was found in some animals, but this was not sustained at 20 weeks and had no functional effects. For Parkinson's disease, the principal aim now is to induce the dopaminergic phenotype in these cells prior to transplantation. However, given the relative safety profile for these human cells and their capacity to extend fibers into the adult rodent brain, they may provide the ideal basis for the repair of other lesions of the CNS where extensive axonal outgrowth is required.

Relative safety and complication profiles of thrombolysis and primary angioplasty in acute myocardial infarction

Summary The safety profile of thrombolytic therapy has been evaluated by several large-scale clinical trials; data on percutaneous coronary angioplasty (PTCA) complications in the context of acute myocardial infarction is more limited. The major life-threatening complication of thrombolytic therapy is cerebral haemorrhage, with an overall incidence of 0.7–1%, but with higher rates in the elderly, hypertensives or patients on anticoagulant therapy, or patients with a previous stroke. Non-life-threatening bleeds occur in 4–20% depending on definition and on whether or not invasive vascular procedures are involved. Allergic reactions occur in 5–7% but are seldom severe. There is a small but significant increase in the risk of cardiac rupture or ventricular septal defect. PTCA-related complications can be divided into cardiac and non-cardiac. Cardiac complications include arrhythmias, coronary dissection and abrupt coronary closure. However, since the starting point in primary PTCA is usually a completely closed vessel, the incremental damage is small. Thrombus displacement to another coronary artery, or left main or proximal right coronary dissection are serious but rare (

The serotonin syndrome associated with paroxetine, an over-the-counter cold remedy, and vascular disease

There is a new, potentially fatal disorder that is infrequently reported. The apparent rareness may be because of a lack of recognition of the syndrome or its predisposing factors. Fluoxetine (Prozac, Dista Products Co, Division of Eli Lilly Co, Indianapolis, IN), sertraline (Zoloft, Roerig Division, Pfizer Inc, New York, NY), and paroxetine (Paxil, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) belong to a new class of antidepressant medication: the serotonin reuptake-inhibitors (SRIs). The relative safety profile of the SRIs has led to their widespread use. However, a syndrome of excessive serotonergic activity, the “serotonin syndrome” (SS), has recently been recognized. It is characterized by changes in mental status, hypertension, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, and tremor. A high index of suspicion is required to make the diagnosis in these acutely ill patients. The most common agents implicated in SS are the monoamine oxidase inhibitors in combination with L-tryptophan or fluoxetine. A case of a patient with significant peripheral vascular disease who developed SS while taking paroxetine and an over-the-counter cold medicine is reported. There have been no prior reports of this interaction. Discontinuation of the offending agents, sedation, and supportive care are the mainstays of treatment. The interactions of serotonin with platelets and vascular endothelium are also discussed.