Pregnancy and fetal outcomes after exposure to mefloquine in the pre- and periconception period and during pregnancy.

BACKGROUND: Pregnant women who travel to malarious areas and their clinicians need data on the safety of malaria chemoprophylaxis. METHODS: The effect of exposure to mefloquine on pregnancy and offspring outcomes was evaluated using the F. Hoffmann-La Roche global drug safety database for the time frame 31 January 1986 through 26 October 2010. We investigated pregnancy and fetal outcomes in maternal, paternal, and both-parent exposure cases with a focus on congenital malformations and fetal loss. The main outcome measures were birth defect prevalence and types of malformations. RESULTS: A total of 2506 cases of mefloquine exposure during pregnancy or in the pre- and periconception period were evaluated. Most cases were maternal prospective (outcome of the pregnancy unknown at the time of reporting; n = 2246 [89.6%]) followed by maternal retrospective cases (outcome of the pregnancy known at the time of reporting; n = 227 [9.0%]), with small numbers of paternal and both-parent exposure cases. Of the total 2246 mefloquine maternal prospective exposures (95.2%), 2139 occurred before conception and/or during the first trimester. Of 1383 maternal prospective cases with known outcome, 978 (70.7%) resulted in delivery, 405 (29.3%) resulted in abortion (112 spontaneous, 293 therapeutic), and 43 resulted in birth defects, corresponding to a birth defect prevalence of 4.39% (43 of 978). Prospective cases overall showed no specific pattern of birth malformations. CONCLUSIONS: 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 rates.

Risk of pneumonia and other complications of influenza-like illness in patients treated with oseltamivir.

BACKGROUND: Clinical trials suggest that the risk of pneumonia and other sequelae of influenza may be reduced in patients using oseltamivir. RESEARCH DESIGN AND METHODS: This retrospective cohort study used U.S. health insurance claims data. Patients were grouped into three cohorts: (1) diagnosed with influenza-like illness (ILI) and received a dispensing of oseltamivir; (2) diagnosed with ILI but received no antiviral medication; and (3) received oseltamivir without a physician diagnosis of ILI. Baseline factors assessed included demographics, history of drug dispensings, diagnoses, and vaccinations. MAIN OUTCOME MEASURES: Outcomes included diagnosis of pneumonia, dispensing of an antibiotic, or hospitalization within 30 days after an ILI diagnosis or oseltamivir dispensing. RESULTS: The adjusted hazard ratio for ILI with oseltamivir compared to ILI without antivirals for pneumonia was 0.72 (95% CI, 0.60-0.86), for antibiotic dispensing was 0.89 (95% CI, 0.86-0.93), and for hospitalization was 0.74 (95% CI, 0.61-0.90). The cohort who received oseltamivir without an ILI diagnosis did not differ significantly in risk of any outcome from the ILI with oseltamivir cohort. CONCLUSIONS: The risk of pneumonia, antibiotic dispensing, and hospitalization was reduced in patients with ILI who received oseltamivir compared to no antiviral therapy. These findings were based on health care claims only and have not been verified through medical record review.

Safety and pharmacology of oseltamivir in clinical use.

Oseltamivir is a novel agent approved for the treatment and prevention of influenza infection and illnesses in adults and children. Assessment of data from the clinical trial programme, a US health insurance database study and postmarketing surveillance allowed a comprehensive review of the safety of oseltamivir in clinical use in subjects >1 year of age. Oseltamivir has been studied over the course of a 5-year development programme in >11000 subjects from North America, Europe and the Southern Hemisphere, including otherwise healthy adults, approximately 500 elderly/high-risk subjects, and children (>1000) aged 1-12 years. Safety evaluations included treatment-emergent adverse events, hospitalisations and deaths, as well as haematological and biochemical laboratory safety tests. The data reveals that oseltamivir has simple, uncomplicated pharmacology and lacks potential for drug-drug interactions. Electrocardiogram parameters, including corrected QT interval, were unaffected by oseltamivir even at high doses. Postmarketing studies confirmed that transient gastrointestinal disturbance is the major adverse effect of oseltamivir and that this can be reduced by taking oseltamivir after a light snack. On treatment serious adverse events were reported in 1.3% of oseltamivir 75mg twice daily, 0.7% of oseltamivir 150 mg twice daily and 1.2% of placebo recipients, respectively, in the clinical trial programme. Postmarketing, it is estimated that, to date, over 4 million oseltamivir prescriptions have been dispensed worldwide. Approximately 2300 spontaneous reports were received by the manufacturer over the three winter seasons of use. As these events are reported infrequently and from an unknown number of users, it is not possible to definitively assess causality or frequency of reported events. Most reports were of gastrointestinal and skin reactions. However, a clear association between the skin reactions and oseltamivir has not been established. A large study of insurance records, which permitted the assessment of the relative risk of medical events treated in the month following prescription of oseltamivir in general use, showed no evidence of increased risk of cardiac, neuropsychiatric or respiratory events for those receiving oseltamivir compared with those who did not. To conclude, no important safety concerns have evolved which might limit the suitability of oseltamivir for the treatment and prevention of influenza in all patient populations.

Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic.

Recent cross species transmission of avian influenza has highlighted the threat of pandemic influenza. Oseltamivir (Tamiflu) has been shown to be effective in the treatment and prevention of epidemic influenza infection in adults, adolescents and children (> or = 1 year). Although oseltamivir has not been approved for prophylactic use in children, it has been shown to be effective. Oseltamivir is also active against avian influenza virus strains. Evidence suggests that lower doses or shorter durations of treatment/chemoprophylaxis other than those approved may not be effective and may contribute to emergence of viral resistance. Safety data from dose ranging studies show that 5 day courses of 150 mg twice daily for treatment and 6 week courses of 75 mg twice daily for prophylaxis were as well tolerated as the approved dose regimens. The use of oseltamivir in a pandemic is influenced by the goals of the pandemic plan developed by the responsible Government and Health Authority. To optimize use of antiviral medications, processes will be needed to collect, collate and report outcome data from treated patients and/or from use for chemoprophylaxis of pandemic influenza during the first-wave outbreaks. If oseltamivir is included in a national or regional pandemic plan, stockpiling of the material, either in the form of capsules or the bulk active pharmaceutical ingredient will be necessary. In the absence of a stockpile, there is no guarantee that an adequate supply of oseltamivir will be available.