Current Drug Safety - Volume 9, Issue 2, 2014

Primary cardiac tumors are uncommon, with an autopsy frequency of 0.001%-0.28%: 75% of them are benign, and 50-75% of these are myxomas. Often the first neurological manifestations of a cardiac myxoma include transient ischemic attacks and ischemic strokes. Although thrombolytic therapy represents the gold standard for acute ischemic stroke treatment, its safety and effectiveness in stroke patients with myxoma is unknown. From the analysis of the literature on thrombolysis in ischemic stroke patients with myxoma we report clinical evidence supporting the use of thrombolytics, and the application of thrombolysis in this setting of patients. 23 previous reports presented patients with acute ischemic stroke and associated cardiac myxoma treated with thrombolytic therapy: 16 patients were treated with intravenous thrombolysis, 4 patients with intra-arterial thrombolysis and 3 patients were treated with bridging therapy (intravenous alteplase followed by local mechanical thrombolysis). Our review showed that the possible risk of major bleeding in these patients resulted in limited and small hemorrhages; furthermore patients who developed cerebral hemorrhage did not deteriorate clinically: waiting for further confirmation and additional data from a future register, these observations may suggest that, notwithstanding a possible publication bias, i.v. thrombolytic therapy may be a safe treatment in these patients.

In the last decade, several third and fourth generation fluoroquinolones (FQs) have been approved for clinical use. These new agents exhibit a more potent and broader-spectrum antibacterial activity and improved pharmacokinetic properties in comparison to the earlier FQs. Although new FQs are generally safe and well tolerated, moderate-to-severe toxicity events have been reported for some of them, leading to their restriction, suspension or even withdrawal from the market. The most common FQ-related adverse effects (AEs) are usually mild and involve the gastrointestinal tract (e.g. nausea and diarrhea) and the central nervous system (e.g. headache and dizziness). Uncommon, but severe AEs (e.g. arthropathy, QTc interval prolongation, dysglycaemia and phototoxicity) and idiosyncratic reactions (e.g. hepatitis and hemolytic anemia) have also been reported and will be discussed throughout this paper. The evidence currently available suggests that AEs can be inherent to the FQ class or can be associated with a particular chemical moiety of the molecular structure of each FQ, thus varying in frequency, severity and nature. The main goal of this review is to provide a systematic evaluation of safety and tolerability data of the newer FQs with emphasis on those currently marketed.

Renin-angiotensin-system (RAS) is an enzymatic cascade that plays a pivotal role in the development of arterial hypertension, kidney disease and cardiovascular disease. Inhibition of the RAS with angiotensin converting enzyme (ACE) inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) has proved to be a successful strategy for the treatment of hypertension and related cardiovascular disorders. However, by reducing feedback inhibition of renin release, the effects of ACE-Is and ARBs lead to an increase in plasma renin concentration (PRC) and activity (PRA), limiting a complete inhibition of the RAS. Consequently the effects of a different pharmacological strategy that completely blocks the RAS upstream has been assessed in the last years. In this context, aliskiren is the first representative of a new class of non-peptide orally active renin inhibitor that blocks the RAS at its rate-limiting step and induces a net reduction in PRA, angiotensin II and aldosterone levels. Aliskiren effectively reduces blood pressure as a monotherapy as well in combination therapy. In addition, aliskiren has a placebo-like tolerability profile at the licensed doses of 150 mg and 300 mg. Aliskiren also exhibits additive effects on blood pressure reduction when combined with drugs that lead to a reactive increase in the PRA, such as diuretics, ACE-Is or ARBs. In previous studies, aliskiren showed beneficial effects in patients with arterial hypertension and associated clinical conditions. However, later trials indicated that the use of aliskiren should be avoided in patients with renal failure or receiving ACE-Is or ARBs. The main aim of this review is to summarize the available data on its efficacy and safety profile, highlighting clinical implications from recent trials.

Premature ejaculation is one of the most prevalent sexual disorders affecting men today. The lack of approved therapies has resulted in the prescription of many ‘off-label’ treatments to manage the condition. Selective serotonin reuptake inhibitors have an interesting side effect of prolonging ejaculatory latency. Consequently, these agents are often considered a first line treatment for patients suffering from premature ejaculation. Erectile dysfunction is another common side effect reported by men treated with selective serotonin reuptake inhibitors. Nitric oxide is the primary mediator of erectile function. Preclinical studies have provided evidence that selective serotonin reuptake inhibitors decrease nitric oxide bioavailability. This invited mini-review aims to examine the physiology of the erectile and ejaculatory responses, discuss the indicated and ‘off-label’ clinical utility of selective serotonin reuptake inhibitors, and to summarize evidence from basic science and clinical studies pertaining to mechanisms of how selective serotonin reuptake inhibitor therapy modifies ejaculatory and erectile function.

Canagliflozin is a newly approved drug for the treatment of type 2 diabetes. This agent lowers blood glucose mainly by increasing urinary glucose excretion through inhibition of sodium glucose co-transporter 2 (SGLT2) in the kidneys. Data derived from randomized clinical trials lasting up to 52 weeks suggest that canagliflozin is generally well tolerated. The most common adverse effects are genital mycotic infections occurring in 11-15% of women exposed to canagliflozin versus 2-4% of those randomized to glimepiride or sitagliptin. In men, corresponding proportions are 8-9% versus 0.5-1%. Urinary tract infections (UTI) are slightly increased (5-7%) with the use of canagliflozin compared with placebo (4%). The risk of hypoglycemia associated with canagliflozin is marginally higher than placebo, but markedly increases when the drug is used in conjunction of insulin or sulfonylureas (SU), in patients with chronic kidney disease (CKD), and in the elderly. Worsening renal function and hyperkalemia may occur in patients using canagliflozin, particularly in patients with underlying CKD. Mild weight loss (mean 2-4 kg) and lowering of blood pressure represent 2 advantages of canagliflozin owing to its osmotic diuretic effect. However, the latter action may lead to postural hypotension and dizziness in susceptible subjects. Another concerning adverse effect of canagliflozin is an average 8% increase in plasma levels of low-density lipoprotein cholesterol (LDL-C) compared with placebo. Overall, canagliflozin is a useful addition for treatment of type 2 diabetes, but its safety needs to be established in long-term clinical trials.

Objective: To explore the type and frequency of the unwanted effects following use of non-steroidal antiinflammatory drugs (NSAIDs) and antibiotics in a gastroenterological out-patient setting. Methods: We analyzed a gastroenterological database which includes 151 inflammatory bowel disease (IBD) patients followed between January 2008 and December 2009. The key-words included NSAIDs and antibiotics. Results: Of 19 cases treated with NSAIDs, 8 displayed convincing evidence linking them with the subsequent development of IBD. Of 44 antibiotic mentions, 7 documents alluded to macrolide prescriptions, which were followed by induction or relapse of IBD in 5; all of the newly diagnosed cases of IBD were endoscopically proven, and one ran a fulminant course requiring emergency colectomy; 4 of 5 prescriptions of amoxycillin/clavulanic acid were accompanied by toxicity (three hepatitides and one reactivated IBD). Overall, the frequency of unwanted effects was 36% for both NSAIDs and antibiotics. Conclusion: We suggest that NSAIDs and antibiotics (specifically of the macrolide structure) can induce gut and hepatic damage, significantly enhancing co-morbidities in gastroenterologic out-patients, with break of cost-containment guidelines. Therefore, caution is advisable in prescribing NSAIDs and antibiotics in this setting. Though retrospective and possibly biased, the current data coincide with both bench work and epidemiological evidence.

Background: Despite the reported widespread use of herbal medicines globally and their benefits, they are not completely without potential to cause harm. The haphazard, irresponsible or non-regulated use of several herbal medicines may put the health of their users at risk of toxicity. Objective: This study aimed to assess the general perception of the safety and occurrence of adverse effects of herbal medicines among residents of Ikorodu in Lagos, Nigeria. Methods: The study population included 400 randomly selected and consented residents in Ikorodu. Data was collected using a standard closed and open-ended structured questionnaire with three (3) sections on socio-demography, safety and adverse effects of herbal medicines. Associations between the variables were determined using Chi square analysis. Results: The results showed that 333 respondents (82.4%) believed that herbal medicines are safe for use and only 39 (9.7%) held the view that they may not be safe. Results also show that 51 (12.6%) of respondents had experienced adverse effects while 250 (61.9%) said they had never experienced adverse effects from the use of herbal medicines. Conclusion: Herbal medicine is popular among the respondents but they appear to be ignorant of its potential toxicities. It may be necessary to educate the consumers of herbal medicines on the potentials for herbs-drugs interaction and adverse effects specially as a result of indiscriminate and unguided use of herbal medicines.

Purpose: The aim of the present investigation is to determine the in vivo potential of previously developed and optimized Cremophor EL free paclitaxel (CF-PTX) formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate. CF-PTX was found to have drug loading of 6 mg/ml similar to Cremophor EL based marketed paclitaxel formulation. In the present study, intracellular uptake, repeated dose 28 days sub-acute toxicity, anti-cancer activity, biodistribution and pharmacokinetic studies were conducted to determine in vivo performance of CF-PTX formulation in comparison to marketed paclitaxel formulation. Methods: Intracellular uptake of CF-PTX was studied using A549 cells by fluorescence activated cell sorting assay (FACS) and fluorescence microscopy. In vivo anti-cancer activity of CF-PTX was evaluated using Ehrlich ascites carcinoma (EAC) model in mice followed by biodistribution and pharmacokinetic studies. Results: FACS investigation showed that fluorescence marker acridine orange (AO) solution showed only 19.8±1.1% intracellular uptake where as significantly higher uptake was observed in the case of AO loaded CF-PTX formulation (85.4±2.3%). The percentage reduction in tumor volume for CF-PTX (72.5±2.3%) in EAC bearing mice was found to be significantly (p<0.05) higher than marketed formulation (58.6±2.8%) on 14th day of treatment. Pharmacokinetic and biodistribution studies showed sustained plasma concentration of paclitaxel depicted by higher mean residence time (MRT; 18.2±1.8 h) and elimination half life (12.8±0.6 h) with CF-PTX formulation as compared to marketed formulation which showed 4.4±0.2 h MRT and 3.6±0.4 h half life. The results of the present study demonstrated better in vivo performance of CF-PTX and this formulation appears to be a promising carrier for sustained and targeted delivery of paclitaxel.

The use of intravitreal injections of anti-Vascular Endothelial Growth Factor (anti-VEGF) has been used for a broad spectrum of ocular pathologic entities. Although the dose of anti-VEGF agents used for treating eye disease is minute compared with that used intravenously, intraocular administration can lead to systemic absorption and reduce serum VEGF levels. Several systemic side effects, such as hypertension and cardiovascular complications have been rarely reported in the literature. Renal complications of intravenous administration of anti-VEGF, are well known and include a variety of renal pathological damage which can induce proteinuria and hypertension. We describe herein, 2 cases of diabetic patients with preexisting kidney disease who presented severe reduction of their renal function after intraocular administration of anti-VEGF. Although a cause –effect correlation cannot be established unless further studies are performed, we believe that pretreatment counseling should include a discussion outlining the possible risk of aggravating of the renal function in patients with kidney disease. Close cooperation with the patient’s nephrologist and close monitoring of the patient may be required, in such cases, in order to monitor the renal function before and after the intravitreal administration of anti-VEGF.

The standard gold care medications for benign prostatic hyperplasia (BPH) are the alpha-1-adrenergic antagonists, they are an effective medications and are generally well tolerated. However, at this time, no data have been published concerning the development of severe rhinorrhea with a great impact on quality of life in patients treated with alpha-1-adrenergic antagonists. We report two men with BPH treated with two different alpha-adrenergic antagonists; alfuzosin and doxazocin. The naranjo quality scale documented a probable adverse drug reaction (score 7) between rhinorrhea and treatmenr with alpha-1-adrenergic antagonists. In conclusion we reported that alpha-1-adrenergic antagonists are able to induce rhinorrhea in patients with BPH.

Meprobamate is usually a safe drug prescribed for anxiety disorders. Fixed drug eruption (FDE) is an exceptional cutaneous adverse effect of this drug. We report a case of FDE induced by meprobamate with positive patch test. A 22-year-old woman was prescribed for depression meprobamate, aceprometazine, valpromide and lorazepam. On the second day of treatment, the patient presented red erythematous and pruriginous plaques in the limbs and the face. After stopping the previous treatment, the patient's lesions resolved completely within 3 weeks with residual pigmentation. One month later, patch tests were performed and were positive to meprobamate. Exceptional cases of FDE were reported in literature with meprobamate. None has reported the use of patch test to confirm the diagnosis.