Adverse Effects

Translated from Rev Prescrire April 2012; 32 nicotine (1). It included 3249 cases of sui- confidence interval (95%CI) 1.4 to 2.7) (1). (342): 268 cide, self-harm and severe depression, The frequency of preeclampsia was 9% 90% involving varenicline, 7% bupropion, in women taking an SSRI and 2.4% in Nicorandil: mucocutaneous and 3% nicotine. controls, and the risk was even higher with ulceration (continued) The authors calculated what proportion venlafaxine (relative risk 4.9, 95% CI: 2.7 these adverse effects represented among to 8.8).  A very severe case report. all other serious adverse effects reported Blood pressure elevation is a well- with each drug. known adverse effect of venlafaxine (2) In 2012, a summary of an Compared to nicotine, this proportion and is one more reason to use antide- exemplary case report of was 8 times higher with varenicline (odds pressants sparingly during pregnancy. adverse effects attributed to ratio 8.4, 95% confidence interval ©Prescrire nicorandil was published in (95%CI): 6.8 to 10.4) and about 3 times the newsletter of the Regional Pharma- higher with bupropion (95%CI: 2.3 to 3.7). Selected references from Prescrire’s literature covigilance Centre in Angers, France (1). The increase persisted after excluding search. Nicorandil 1- “Venlafaxine, pre-eclampsia, eclampsia and relat- has minor efficacy as a symp- reports in which the patient was also tak- ed disorders of pregnancy” WHO Pharmaceuticals tomatic treatment for angina pectoris. It is ing one or more of the other 58 drugs for Newsletter 2012; (1): 19-21. known to cause sometimes severe ulcer- which, according to the US summaries of 2- Prescrire Editorial Staff “Venlafaxine and gener- alised anxiety disorder: minimise recourse to drugs” ation of the skin and mucosae (2). product characteristics, suicide is an Prescrire Int 2001; 10 (55): 131-134. An 87-year-old woman who had been adverse effect. taking nicorandil since 2003 developed In practice, varenicline and bupropion severe aphthous stomatitis in mid-2009 (1). both have an unfavourable harm-benefit Translated from Rev Prescrire May 2012; 32 Nicorandil was discontinued in July 2009 balance. When a smoker needs a drug to (343): 352 and the lesions healed within a month. In help him or her quit, it is best to use nico- August, nicorandil was reintroduced. tine (2). Benfluorex: lesions In December 2009, a sigmoidouterine fis- ©Prescrire on a bioprosthetic heart tula was diagnosed. In March 2011, a valve too colostomy was performed. Then, a vesico- Selected references from Prescrire’s literature vaginal fistula was diagnosed. The stoma search.  A troubling case. 1- Moore TJ et al. “Suicidal behaviour and depres- area became ulcerated in August 2011. sion in smoking cessation treatments” Plos One 2011; Nicorandil was withdrawn in August 6 (11): 7 pages. In early 2012, a French team 2011. By late September 2011, the ulcer- 2- Prescrire Rédaction “19-5. Patients en cours de published a troubling case sevrage tabagique” Rev Prescrire 2011; 31 (338 suppl. ation around the stoma had improved interactions médicamenteuses). report involving a 40-year- and the pain had stopped. By November old woman who underwent 2011, it has almost completely healed. heart valve replacement surgery twice In view of nicorandil’s minor efficacy in Translated from Rev Prescrire May 2012; 32 while taking benfluorex (formerly mar- angina, these adverse effects are unac- (343): 352 keted under the brand name Mediator° ceptable: patients would be better served among other names) (1,2). if nicorandil were neither prescribed, used Venlafaxine: preeclampsia After 15 months of benfluorex therapy, nor licensed. and eclampsia the patient was diagnosed with mitral ©Prescrire valve regurgitation, and a bioprosthetic  Gestational hypertension. valve was implanted. Selected references from Prescrire’s literature Benfluorex was reintroduced, and the search. In early 2012 the World patient continued treatment for 33 months. 1- “Ulcérations cutanéomuqueuses et fistules sous nicorandil” Actualités en pharmacovigilance 2012; (45). Health Organization’s phar- Cardiac problems developed a second www.univ-angers.fr accessed 19 February 2012: macovigilance centre in time. She was diagnosed with mitral and 2 pages. Uppsala published an analy- aortic regurgitation, and both valves were 2- Prescrire Editorial Staff “Painful chronic ulcera- tion linked with nicorandil: the vagina too” Prescrire sis of 31 cases of hypertensive disorders replaced with mechanical valves. The Int 2010; 19 (110): 257. attributed to venlafaxine in pregnant lesions on the bioprosthetic mitral valve women (1). They derived from the inter- resembled those on the native aortic valve, national Vigibase database. There were including thickening similar to lesions attrib- Translated from Rev Prescrire April 2012; 32 4 cases of eclampsia, 21 of preeclampsia, uted to benfluorex or observed in patients (342): 271 6 of gestational hypertension and 2 of the with carcinoid tumours. No other possible Hellp syndrome (severe preeclampsia, causes of valvular heart disease were Varenicline and bupropion: haemolysis, thrombocytopenia and liver identified, such as the use of other amphet- suicide damage). Only 3 of the women were amine appetite suppressants or ergot under 29 years old. The daily doses of derivatives.  An analysis of reports in the USA. venlafaxine ranged from 9 to 300 mg Benfluorex therefore also appears to and the treatment period ranged from provoke serious valvular injury, even to In late 2011 a study based 19 days to several years. porcine bioprosthetic valves. on reports made between A cohort study of 5731 women showed In cases of valvular insufficiency, even 1998 and 2010 to the US that the risk of gestational hypertension those involving a bioprosthetic valve, ben- Food and Drug Administra- was roughly twice as high among women fluorex should be systematically suspect- tion (FDA) analysed reactions in patients taking a selective serotonin reuptake ed as the causative agent, along with other taking drugs used for smoking cessa- inhibitor antidepressant as in women not drugs known to damage heart valves. tion, namely varenicline, bupropion and taking such drugs (odds ratio 1.9, 95% ©Prescrire

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