Adverse gastrointestinal events

NSAIDs share several unwanted side effects. The most notorious is the risk for serious adverse gastrointestinal events including gastric or intestinal ulceration. Eor gastrointestinal bleeding associated... 

Ivermectin was generally well tolerated. Quantitative pupillometry ruled out any mydriatic effect of ivermectin. There was no nervous system toxicity associated with oral ivermectin at any of the doses. There were no serious clinical or laboratory adverse events. Three of the fifty-one subjects who took ivermectin fasted reported minor adverse gastrointestinal events fecal abnormality (n = 1), nausea (n = 1), and vomiting (n — 1) six reported minor neurological adverse events headache (n = 4), anxiety n — V), and dizziness n — 1). There were no adverse events in the subjects who took ivermectin 120 mg. The absorption of ivermectin was about 2.5 times higher when it was given after a high-fat meal. 

The conclusion of a meta-analysis of 16 studies was that NSAID users have an approximately three-fold greater relative risk of developing serious adverse gastrointestinal events than non-users (64). This has been confirmed by a review (65). 

Adverse gastrointestinal events are not uncommon in early clinical trials because one objective of these studies is to assess tolerability however, these effects are not always related to the pharmacology of the compound. Of the top 100 most frequently prescribed medications, 44 have been implicated in episodes of acute pancreatitis (Trivedi and Pitchumoni 2005). There is an objective to improve assessment of gastrointestinal toxicities by biochemical analyses in addition to enhancing safety pharmacology studies. Many of the mechanisms that cause gastrointestinal and pancreatic toxicity are poorly understood. 

The tolerabihty of azithromycin oral suspension, 10 mg/ kg od for 3 days, has been assessed in children in a review of 16 multicenter studies (7). Of 2425 patients, 1213 received azithromycin and 1212 received other drugs. The incidence of treatment-related adverse events was significantly lower in those who took azithromycin, while withdrawal rates were similar. There were significantly fewer gastrointestinal events with azithromycin and their duration was significantly shorter. 

Since timolol has been satisfactorily used by millions of patients, the incidence of serious gastrointestinal events appears to be very low. Absence of symptoms after betaxolol therapy in this patient is in agreement with its lower risk of non-cardiac adverse reactions compared with the non-selective agent timolol. 

The safety of cyclic etidronate has been evaluated in 550 general practices in the UK in 7977 patients taking cyclic etidronate (7244 women) (35). The findings were consistent with the conclusions of several reviews of the safety and tolerability of cyclic etidronate (36,37). The most common adverse effects reported in these reviews were minor gastrointestinal events, such as diarrhea, nausea, and flatulence. Etidronate has not been associated with an increased incidence of serious gastrointestinal adverse events. 

Headache, dizziness, and gastrointestinal symptoms are the most frequent adverse effects clinically significant gastrointestinal events include upper gastrointestinal ulceration, with or without hemorrhage or perforation (SEDA-20, 94) (SEDA-21, 107). The profile of drug interactions is similar to the profiles of other NSAIDs (SEDA-21,108). 

The efficacy of adjunctive therapy with remacemide has been evaluated in 11 children (4). Remacemide was well tolerated in doses up to 13.5 mg/kg/day. The most common adverse events were dizziness, ataxia, and gastrointestinal events. One patient died after a suspected seizure, which was unlikely to have been related to remacemide. 

As expected with a cyclo-oxygenase inhibitor, the adverse effects most frequently reported by patients taking tenidap sodium were gastrointestinal serious gastrointestinal events occurred in 2.1% (1). 

SSZ is another DMARD often used in the treatment of RA. It is estimated that 20-30 % of RA patients on SSZ report adverse drug reactions. Adverse drug events of SSZ are gastrointestinal and hematologic. 

Another public health implication is the health costs associated with management of adverse events related to opioid use. In a retrospective analysis, costs related to opioid-induced gastrointestinal events in 237 447 patients were analysed. Increased costs resulted from more hospitalizations, more days in hospital, more emergency department or outpatient visits, and more prescription claims, compared with those with gastrointestinal events. The authors commented that gastrointestinal events coincident with opioid treatment carry a significant economic burden [27 ]. 

Of 1073 patients aged over 66 years (24% over 81 years) in the US Cubicin Outcomes Registry, 67 (6.2%) had adverse events that were possibly related to daptomycin, and 30 (2.8%) stopped taking it because of an adverse event [132 ]. The most common adverse events were a raised CK activity (2.2%), gastrointestinal events (2.1%), and rashes (0.8%) the most common events that led to withdrawal were a raised CK activity (n = 5), rashes (n = 3), rhabdomyol-ysis ( = 3) and renal impairment (n = 3). 

Observational studies Prucalopride has been evaluated in an open long-term study in 1455 patients (90% women) with chronic constipation for up to 24 months 8% stopped taking prucalopride because of adverse events, mostly gastrointestinal events (3.3%) and headache (1%) [15 ]. During the first 3 months, the most frequent adverse events that led to prucalopride withdrawal were abdominal pain, diarrhea, nausea, and headache, which accounted for 74% of withdrawals because of adverse reactions (43 out of 58). Most of these events (30 out of 43) occurred in... 

The ATHENA trial was a placebo-con-trolled, double-blind, parallel-arm trial to assess the efficacy of dronedarone 400 mg bd for the prevention of cardiovascular hospitalization or death from any cause in patients with atrial fibrillation/atrial flutter [60 ]. Treatment was prematurely withdrawn in 696 of the 2301 patients (30%) taking dronedarone, compared with 716 of the 2327 (30.8%) taking placebo. The main reasons were treatment-emergent adverse events (in 13% of those taking dronedarone versus 8.1% of those taking placebo), gastrointestinal events (26% versus 22%), skin related events (10% versus 7.6%), raised serum creatinine (4.7% versus 1.3%), and QT interval prolongation (1.7% versus 0.6%). 

In patients having Parkinson s disease, both entacapone and tolcapone potentiate the therapeutic effect of L-dopa and prolong the daily ON time by 1-2 h. In the clinic, COMT inhibitors have been well tolerated, and the number of premature terminations has been low. In general, the incidence of adverse events has been higher in tolcapone-treated patients than in entacapone-treated patients. The main events have comprised of dopaminergic and gastrointestinal problems [2,3]. 

A statin combined with a resin results in similar reductions in LDL cholesterol as those seen with ezetimibe. However, the magnitude of triglyceride reduction is less with a resin compared to ezetimibe, and this should be considered in patients with higher baseline triglyceride levels. In addition, gastrointestinal adverse events and potential drug interactions limit the utility of this combination. 

NSAIDs are one of the most widely used classes of medications in the United States, particularly in the elderly.4 More than 20,000 deaths occur in the United States per year as a direct result of adverse events related to NSAID use. Chronic NSAID ingestion leads to symptoms of nausea and dyspepsia in nearly half of patients. Peptic ulceration occurs in up to 30% of patients who use NSAIDs chronically, with gastrointestinal bleeding or perforation occurring in 1.5% of patients who develop an ulcer. NSAID-related peptic ulcers usually occur in the stomach duodenal ulcers are much less common. 

Gastrointestinal adverse events reported with lubiprostone include nausea, diarrhea, abdominal distention, abdominal pain, flatulence, vomiting, loose stools, and dyspepsia. Nausea is a prominent adverse effect and may be minimized when lubiprostone is taken with food. 

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