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Home , Benfluorex, Nicorandil

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 , 7% , 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 (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 . 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 pectoris. It is ing one or more of the other 58 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 were Varenicline and bupropion: haemolysis, thrombocytopenia and 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

PAGE 240 • PRESCRIRE INTERNATIONAL OCTOBER 2012/VOLUME 21 N° 131 Downloaded from english.prescrire.org on 27/09/2021 Copyright(c)Prescrire. For personal use only. Translated from Rev Prescrire June 2012; 32 des psychotropes, compte rendu de la réunion du Selected references from Prescrire’s literature mardi 16 June 2011. Évaluation du potentiel d’abus search. (344): 428 et de dépendance des spécialités à base de méthyl- 1- Prescrire Editorial Staff “Benfluorex: how many 20 phénidate” 6 December 2011. afssaps.fr (now deaths?” Prescrire Int 2011; (113): 45. ansm.sante.fr) accessed 18 April 2012: 13 pages. 2- Ayme-Dietrich E et al. “Mitral bioprosthesis : hypertrophic scaring and native aortic valve fibro- abuse and addiction sis during benfluorex therapy” Fundam Clin Phar- macol 2012; 26 (2): 215-218.  In young adults and adolescents. Translated from Rev Prescrire June 2012; 32 (344): 428 Translated from Rev Prescrire April 2012; 32 Methylphenidate is an (342): 268 marketed for Pelargonium: the treatment of some forms severe liver damage SSRI antidepressants: of attention deficit-hyperac- persistent pulmonary tivity disorder and narcolepsy (1,2). Its use  Harmful plants. hypertension in newborns is only justified in rare, severe cases. (continued) In February 2012 the French Health Root extracts of Pelargonium Products Agency released a report on the sidoides and P. reniforme are 16 June 2011 meeting of the National sometimes used to treat cer-  Consistent data. committee on narcotics and psychotrop- tain respiratory or ENT dis- ics concerning methylphenidate (2). orders, despite the lack of proven efficacy. In January 2012, the results Between 2006 and 2011, 83 cases of In France, these products are marketed as of a European cohort study abuse, addiction or off-label use were dietary supplements (1,2). including 1.6 million neo- reported to the network of French Centres In late 2011, the independent German nates born after 33 weeks of for Evaluation and Information on Phar- pharmacovigilance centre Arznei- gestation were published (1). About macodependence or to the companies. Telegramm reported a case of liver dam- 11 000 women had used a selective sero- Only 21 such reports were received age attributed to a plant belonging to the tonin reuptake inhibitor (SSRI) antide- between 2000 and 2006. genus Pelargonium (3). pressant after week 20 of pregnancy. This misuse involved the immediate- A 30-year-old woman took Pelargonium Three per 1000 exposed newborns had and sustained-release formulations. Most root extracts (unknown species) for 4 days. persistent , ver- of the individuals concerned were young One day after the end of treatment, she sus 1.2 per 1000 unexposed newborns adults (19 to 29 years, 28%) or adoles- developed liver damage with jaundice, (statistically significant difference). Two cents (20%). dark urine, hyperbilirubinaemia and studies conducted since 1996 had already The reported reasons for methylphe- transaminase levels more than 35 times demonstrated this increased risk (2). All nidate consumption included attention the upper limit of normal. No other poten- of the SSRIs used carried a similar deficit disorder, sleep disorders, anxiety tial causes of hepatitis were found. risk (1). and depression, agitation, improved In March 2012, the German drug reg- In 2010, the European Medicines mental performance, replace- ulatory agency published a review includ- Agency (EMA) reported that the inci- ment, effects, weight loss, and ing approximately 30 reports of liver dam- dence of persistent pulmonary hyperten- doping. age that were attributed to Pelargonium sion after in utero exposure to an SSRI The doses ranged from 10 mg to and registered in the German national antidepressant was 5 cases per 1000 2520 mg per day. Methylphenidate was database up to January 2012 (4). There births (3). The incidence in the general taken for various periods (up to 20 years were 11 cases of hepatitis and 8 cases of population is 1 to 2 per 1000 births. in one case). The route of administration jaundice. One patient received a liver According to the EMA, the same pre- was intravenous in 10 cases, subcuta- transplant. Some of the patients were cautions should be taken during preg- neous in 1 case, and intranasal in also taking known hepatotoxic drugs nancy with other serotoninergic antide- 6 cases. (paracetamol, , ). pressants: duloxetine, mirtazapine and Systemic adverse effects included neu- In practice, “natural” is not synonymous venlafaxine. ropsychological and cardiac disorders. with safe, even when it comes to plants. This is yet another reason to frequent- Withdrawal symptoms were also report- Patients with unexplained symptoms ly weigh the benefits against the potential ed, along with local adverse effects at the should also be asked whether they use harms of antidepressant therapy through- site of administration. herbal preparations (5). out pregnancy. The French committee on narcotics ©Prescrire ©Prescrire and psychotropics concluded that methylphenidate “is trivialised, both by Selected references from Prescrire’s literature prescribers and by students in schools, search. Selected references from Prescrire’s literature 1- search. where the product is already circula- EMA “Assessment report on Pelargonium 1- Kieler H et al. “Selective serotonin reuptake sidoides DC and/or Pelargonium reniforme Curt., inhibitors during pregnancy and risk of persistent ting”. radix” 31 March 2011. www.ema.europa.eu accessed 13 April 2012: 38 pages. pulmonary hypertension in the newborn: popu- What measures are being taken to 2- lation based cohort study from the five Nordic “Arkogélule Pelargonium” ClickaDoc Premier 344 warn them of the dangers? accessed 16 April 2012: 1 page. countries” BMJ 2011; : 9 pages. 3- 2- Prescrire Rédaction “Antidépresseurs IRS: hyper- ©Prescrire “Liver damage with Umckaloabo” Arznei- telegramm 2011; 42 (7): 63. tension artérielle pulmonaire du nouveau-né” Rev 4- Prescrire 2008; 28 (291): 26. “Hepatotoxische reaktionen im Zusammenhang 3- European Medicines Agency “Pharmacovigilance Selected references from Prescrire’s literature mit der Anwendung von Pelargonium-haltigen Working Party, March 2010 plenary meeting” search. arzneimitteln” Bulletin zur Arzneimittelsicherheit. Infor- 1- Prescrire Rédaction “Hyperactivité avec déficit mationen aus BfArM und PEI 2012; 1: 6-7. 25 March 2010. www.ema.europa.eu accessed 5- 21 April 2010: 15 pages. de l’attention: gare au dérapage (suite)” Rev Prescrire Prescrire Rédaction “Bien utiliser les plantes en 2004; 24 (249): 289-291. situations de soins” Rev Prescrire 2007; 27 (286): 2- Afssaps “Commission nationale des stupéfiants et inside back cover.

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