Use of mefloquine in children - a review of dosage, pharmacokinetics and tolerability data

Currently available data provide a scientific basis for the use of mefloquine in small children in the chemoprophylaxis setting and as a part of treatment regimens for children living in endemic areas

Pregnancy and Fetal Outcomes After Exposure to Mefloquine in the Pre- and Periconception Period and During Pregnancy

Pregnant women who travel to malarious areas and their clinicians need data on the safety of malaria chemoprophylaxis. The drug safety database analysis of mefloquine exposure in pregnancy showed that the birth defect prevalence and fetal loss in maternal, prospectively-monitored cases were comparable to background rate

The position of mefloquine as a 21st century malaria chemoprophylaxis

BACKGROUND: Malaria chemoprophylaxis prevents the occurrence of the symptoms of malaria. Travellers to high-risk Plasmodium falciparum endemic areas need an effective chemoprophylaxis. METHODS: A literature search to update the status of mefloquine as a malaria chemoprophylaxis. RESULTS: Except for clearly defined regions with multi-drug resistance, mefloquine is effective against the blood stages of all human malaria species, including the recently recognized fifth species, Plasmodium knowlesi. New data were found in the literature on the tolerarability of mefloquine and the use of this medication by groups at high risk of malaria. DISCUSSION: Use of mefloquine for pregnant women in the second and third trimester is sanctioned by the WHO and some authorities (CDC) allow the use of mefloquine even in the first trimester. Inadvertent pregnancy while using mefloquine is not considered grounds for pregnancy termination. Mefloquine chemoprophylaxis is allowed during breast-feeding. Studies show that mefloquine is a good option for other high-risk groups, such as long-term travellers, VFR travellers and families with small children. Despite a negative media perception, large pharmaco-epidemiological studies have shown that serious adverse events are rare. A recent US evaluation of serious events (hospitalization data) found no association between mefloquine prescriptions and serious adverse events across a wide range of outcomes including mental disorders and diseases of the nervous system. As part of an in-depth analysis of mefloquine tolerability, a potential trend for increased propensity for neuropsychiatric adverse events in women was identified in a number of published clinical studies. This trend is corroborated by several cohort studies that identified female sex and low body weight as risk factors. CONCLUSION: The choice of anti-malarial drug should be an evidence-based decision that considers the profile of the individual traveller and the risk of malaria. Mefloquine is an important, first-line anti-malarial drug but it is crucial for prescribers to screen medical histories and inform mefloquine users of potential adverse events. Careful prescribing and observance of contraindications are essential. For some indications, there is currently no replacement for mefloquine available or in the pipeline

Challenging Varieties of Capitalism's Account of Business Interests: The New Social Market Initiative and German Employers' Quest for Liberalization, 2000-2014

Do employers in coordinated market economies (CME's) actively defend the non-liberal, market- constraining institutions upon which their strategic coordination and competitive success depends? This paper revisits the debate over firms' employer preferences with an in-depth examination of employers in Germany - a paradigmatic CME and crucial "test case" for Varieties of Capitalism. It is based on interviews with key officials and an in-depth examination of a large-scale campaign - the New Social Market Initiative or INMS - founded and funded by German metalworking employers to shape public opinion. The paper argues that German employers have a strong preference for liberalization: they have pushed hard for the liberalization of labor markets, the reduction of government expenditures, the expansion of market-oriented freedoms, and cuts to social protection, employment protection and benefit entitlements. I find no empirical support for the claim that the INSM is an attempt to appease discontented firms within employers' associations. On the contrary: for many employers, the Agenda 2010 reforms did not go far enough. Following the discrediting of the Anglo-American model in the financial crisis, far-reaching concessions by employees, and the unexpected revitalization of the German economy, employers have moderated their demands - but liberalization remains their default preference. This paper also addresses the role of ideas and the conditions under which employer campaigns can influence policy.Verteidigen Arbeitgeber in koordinierten Marktwirtschaften aktiv die nichtliberalen, marktbeschränkenden Institutionen, von denen ihre Möglichkeiten zur strategischen Koordination und ihr Erfolg im Wettbewerb abhängen? Mit einer umfassenden Untersuchung der Präferenzen von Arbeitgebern in Deutschland, das als typisches Beispiel einer koordinierten Marktwirtschaft und wegweisender "Testfall" für die Theorie über Spielarten des Kapitalismus gilt, greift dieses Discussion Paper die Debatte über die Präferenzen von Unternehmen in ihrer Eigenschaft als Arbeitgeber auf. Es basiert auf Interviews mit führenden Arbeitgeberfunktionären sowie einer detaillierten Untersuchung der Initiative Neue Soziale Marktwirtschaft (INSM): einer groß angelegten, von deutschen Metallarbeitgebern initiierten und finanzierten Kampagne zur öffentlichen Meinungsbildung. Der Beitrag belegt eine deutliche Präferenz deutscher Arbeitgeber für die Liberalisierung. Mit Nachdruck haben sie sich für eine Liberalisierung der Arbeitsmärkte, eine Senkung der Staatsausgaben und eine Ausweitung marktorientierter Gestaltungsfreiheiten ebenso eingesetzt wie für Einschnitte bei der sozialen Sicherung, dem Kündigungsschutz und den Versorgungsansprüchen. Die Behauptung, die INSM sei ein Versuch, unzufriedene Unternehmen innerhalb der Arbeitgeberverbände zu beschwichtigen, lässt sich durch die empirischen Befunde nicht stützen. Im Gegenteil: Vielen Arbeitgebern gingen die Reformen im Zuge der Agenda 2010 nicht weit genug. Zwar haben die deutschen Arbeitgeber nach der Diskreditierung des angloamerikanischen Modells während der Finanzkrise, weitreichenden Zugeständnissen seitens der Arbeitnehmer sowie der unerwarteten Wiederbelebung der deutschen Wirtschaft ihre Forderungen gemäßigt - doch bleibt ihre grundlegende Präferenz für die Liberalisierung bestehen. Dieser Beitrag befasst sich außerdem mit der Rolle von Ideen sowie den Bedingungen, unter denen Arbeitgeberkampagnen politische Maßnahmen beeinflussen können

Eye disorders reported with the use of mefloquine (Lariam(®)) chemoprophylaxis--A drug safety database analysis

BACKGROUND Between 80 and 90 million travellers visit malaria endemic areas annually and many require malaria chemoprophylaxis. The characterization of the risk and nature of eye disorders occurring during the use of malaria chemoprophylaxis is relevant for travel medicine advisors. METHODS We did a database analysis on eye disorder adverse events reported for mefloquine (as Lariam®) using the F. Hoffmann-La Roche global drug safety database for the time frame February 1984 to January 18th, 2011. These adverse event reports were reviewed by a trained ophthalmologist. The analysis focused on 3 categories of eye disorders--Category 1: visual acuity; Category 2: anatomical parts of the eye and Category 3: neuro-ophthalmic events. To put our analysis in context, an extensive literature search on "mefloquine" and "eye disorders" was conducted. RESULTS A total of 591 cases with 695 events assigned to the "Eye disorder" SOC in individuals exposed to mefloquine chemoprophylaxis were reported. The highest proportion of events (n = 493, 70.9%) was in Category 1: visual acuity (mainly visual impairment and blurred vision), followed by Category 3: neuro-ophthalmic events (n = 124, 17.8%). The majority of visual adverse events were non-serious but 37.7% (n = 223) of cases were classified as serious. Nine events of maculopathy were reported and 48 cases with 53 events described symptoms of optic neuropathy. CONCLUSIONS Mefloquine, like other anti-malarials, may be associated with eye disorders. Prescribers of anti-malarials should inform travellers regarding the risk of potential ocular side effects. Users of chemoprophylaxis who experience visual disorders should be referred to an ophthalmologist

Antimalarial chemoprophylaxis and the risk of neuropsychiatric disorders

Case reports and epidemiological studies have associated the use of mefloquine with neuropsychiatric adverse events.; We used the General Practice Research Database to conduct a follow-up study with a nested case-control analysis. We assessed the risk of developing first-time anxiety, stress-related disorders/psychosis, depression, epilepsy or peripheral neuropathies in patients using mefloquine, chloroquine and/or proguanil, or atovaquone/proguanil for malaria chemoprophylaxis, as compared to unexposed travelers.; Compared to non-users of antimalarials, the adjusted odds ratio in the nested case-control analysis for users of mefloquine, chloroquine and/or proguanil, or atovaquone/proguanil were 0.71 (95% CI 0.56-0.90), 1.04 (95% CI 0.74-1.46), and 0.73 (95% CI 0.61-0.86) for anxiety or stress-related disorders combined, 0.54 (95% CI 0.41-0.71), 1.06 (95% CI 0.71-1.59), and 0.75 (95% CI 0.62-0.91) for depression, 0.69 (95% CI 0.35-1.36), 1.41 (95% CI 0.54-3.67), and 0.75 (95% CI 0.42-1.36) for epilepsy, and 1.22 (95% CI 0.50-2.99), 1.59 (95% CI 0.41-6.15), and 1.05 (95% CI 0.54-2.03) for neuropathies, respectively. The risk of all outcomes was higher in females than in males across all exposure categories.; The risk of neuropsychiatric disorders was similar for users and for non-users of anti-malarial chemoprophylaxis, with evidence for elevated risks in some subgroups

Use of anti-malarial drugs and the risk of developing eye disorders

Ocular toxicity was described in the late 1950s for some anti-malarial drugs, but only limited information is available on the comparison of ocular toxicity of different anti-malarials.; We conducted a follow-up study with a nested case-control analysis using the General Practice Research Database to compare the risk of developing a first-time diagnosis of an eye disorder during exposure of mefloquine, chloroquine and/or proguanil or atovaquone/proguanil use to non-users. We calculated incidence rates with 95% confidence intervals (CI) and odds ratios using multivariate conditional logistic regression analyses.; We included 83,148 patients and identified 652 cases with an incident eye disorder. The incidence rates with 95% CI of all eye disorders combined in users of mefloquine, chloroquine and/or proguanil, atovaquone/proguanil or travellers not using anti-malarials were 5.3 (4.3-6.5), 7.1 (5.0-9.9), 6.3 (5.6-7.2) and 5.1 (4.6-5.7), per 1000 person-years, respectively. As compared to non-users of anti-malarials, the adjusted odds ratio with 95% CI in the nested case-control analysis for users of mefloquine, chloroquine and/or proguanil, or atovaquone/proguanil were 1.33 (1.01-1.75), 1.61 (1.06-2.45), and 1.25 (1.03-1.52), respectively.; The study provides evidence that there was an increased risk of eye disorders in users of all anti-malarials compared to non-users of anti-malarials