The authors of the FDA analysis note that "given the large number of comparisons made in this review, chance is a very plausible explanation for this difference". The more complete data submitted later by the sertraline manufacturer Pfizer indicated increased suicidal behavior. Similarly, the analysis conducted by the UK MHRA found a 50% increase of odds of suicide-related events, not reaching statistical significance, in the patients on sertraline as compared to the ones on placebo. Overdose
Acute overdosage is often manifested by emesis, lethargy, ataxia, tachycardia and seizures. Plasma, serum or blood concentrations of sertraline and norsertraline, its major active metabolite, may be measured to confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities. As with most other SSRIs its toxicity in overdose is considered relatively low. Interactions
As with other SSRIs, sertraline may increase the risk of bleeding with NSAIDs (ibuprofen, naproxen, mefenamic acid), antiplatelet drugs, anticoagulants, omega-3 fatty acids, vitamin E, and garlic supplements due to sertralines inhibitory effects on platelet aggregation via blocking serotonin transporters on platelets. Sertraline, in particular, may potentially diminish the efficacy of levothyroxine.Sertraline is a moderate inhibitor of CYP2D6 and CYP2B6 in vitro. Accordingly, in human trials it caused increased blood levels of CYP2D6 substrates such as metoprolol, dextromethorphan, desipramine, imipramine and nortriptyline, as well as the CYP3A4/CYP2D6 substrate haloperidol. This effect is dose-dependent; for example, co-administration with 50 mg of sertraline resulted in 20% greater exposure to desipramine, while 150 mg of sertraline led to a 70% increase.
The drug should not be used in children under two years of age, people with kidney disease, or people who are allergic to aspirin.Side effects are primarily gastrointestinal but may also include headache; GI effects include nausea, diarrhea and abdominal pain. There have been scattered reports of various problems when the oral form is used, including: problems caused by myelosuppression (leukopenia, neutropenia, agranulocytosis, aplastic anaemia, and thrombocytopenia), as well as hair loss, peripheral neuropathy, pancreatitis, liver problems, myocarditis and pericarditis, allergic and fibrotic lung reactions, lupus erythematosus-like reactions and rash (including urticaria), drug fever, interstitial nephritis and nephrotic syndrome, usually reversible on withdrawal. Very rarely, use of mesalazine has been associated with an exacerbation of the symptoms of colitis, Stevens Johnson syndrome and erythema multiforme. Chemistry
Mesalazine is the active moiety of sulfasalazine, which is metabolized to sulfapyridine and mesalazine. It is also the active component of the prodrug balsalazide along with the inert carrier molecule 4-aminobenzoyl-beta-alanine. It is in the category of disease-modifying antirheumatic drugs (DMARDs) family of medications. It is unclear exactly how it works. Mechanism of action
Exact mechanism of mesalazine is unknown, but is speculated that mesalazine decreases synthesis of prostaglandin and leukotriene, modulating the inflammatory response derived from the cyclooxygenase and lipooxygenase pathways. It appears to act locally on colonic mucosa. Society and culture
Brand names
Mesalazine is sold under various names including Apriso, Asacol, Asacol HD, Canasa, Delzicol, Fivasa, Lialda, Pentasa, Rowasa, and Sfrowasa. References
External links
"Mesalamine". Drug Information Portal. U.S. National Library of Medicine.