Predictors of quit success in Belgian participants of a varenicline observational smoking cessation study.

BACKGROUND: We evaluated efficacy, predictors of quitting success and the safety profile of varenicline for smoking cessation in the Belgian participants in an observational, "real world" study. METHODS: In this post-hoc analysis of a prospective, observational, non-comparative study, participants were adult smokers who were motivated to quit and were prescribed varenicline in accordance with the recommendations of the European Summary of Product Characteristics. The 7-day point prevalence of abstinence at Weeks 12 and 24 was determined based on patient reporting, and these data were further analysed by time to first cigarette on waking and by the use of behavioural support. The safety profile of varenicline was also assessed. RESULTS: Overall, 61.1% of participants (n= 226) successfully quit smoking by the end of Week 12. There was a significant association between abstinence and time to first cigarette on waking (Week 12: OR, 0.69 [95% CI, 0.50-0.94], p = 0.02; Week 24: OR, 0.70 [95% CI, 0.52-0.94], p=0.02) and the use of behavioural support (Week 12: OR, 6.18 [95% CI, 3.41-11.2], p<0.01; Week 24: OR, 5.37 [95% CI, 2.89-9.98], p<0.01). The most frequent treatment-emergent adverse event was nausea (9.3%). CONCLUSIONS: In this post-hoc analysis, varenicline was an effective smoking cessation aid with an acceptable safety profile in real world clinical practice in Belgian smokers. Significant predictors of abstinence were time to first cigarette on waking and use of behavioural support.

Long-term sertraline treatment of children and adolescents with obsessive-compulsive disorder.

OBJECTIVE: To evaluate the safety and effectiveness of sertraline in the long-term treatment of pediatric obsessive-compulsive disorder (OCD). METHOD: Children (6-12 years; n= 72) and adolescents (13-18 years; n = 65) with DSM-III-R-defined OCD who had completed a 12-week, double-blind, placebo-controlled sertraline study were given open-label sertraline 50 to 200 mg/day in this 52-week extension study. Concomitant psychotherapy was allowed during the extension study Outcome was evaluated by the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), National Institute of Mental Health Global Obsessive-Compulsive Scale, and Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) scores. RESULTS: Significant improvement (p < .0001) was demonstrated on all four outcome parameters on an intent-to-treat analysis for the overall study population (n = 132), as well as the child and the adolescent samples. At endpoint, 72% of children and 61% of adolescents met response criteria (>25% decrease in CY-BOCS and a CGI-I score of 1 or 2). Significant (p < .05) improvements were also demonstrated from the extension study baseline to endpoint on all outcome parameters in those patients who received sertraline during the 12-week, double-blind acute study. Long-term sertraline treatment was well tolerated, and there were no discontinuations due to changes in vital signs, laboratory values, or electrocardiograms. CONCLUSION: Sertraline (50-200 mg/day) was effective and generally well tolerated in the treatment of childhood and adolescent OCD for up to 52 weeks. Improvement was seen with continued treatment.

Evaluation of interaction between fluconazole and an oral contraceptive in healthy women.

OBJECTIVE: To evaluate the potential pharmacokinetic interaction between 2 x 150 mg fluconazole administered once weekly and an oral contraceptive (OC) containing ethinyl estradiol and norethindrone. METHODS: A placebo-controlled, double-masked, randomized, two-way crossover study was used to investigate the pharmacokinetic interaction between 300 mg fluconazole once weekly and the OC Ortho Novum 7/7/7 (Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ) in 26 healthy women, 18-36 years old. In the first cycle (28 days), subjects received OC only. In the second cycle, subjects were assigned randomly to receive OC-fluconazole or OC-placebo. In the third cycle, subjects were crossed over to the opposite treatment. RESULTS: Data for 21 subjects who completed the study were included in the pharmacokinetic analysis; data for all 26 subjects were included in the safety analysis (26 OC only; 24 OC-fluconazole; 23 OC-placebo). Treatment with OC-fluconazole resulted in small but statistically significant increases in 0-24 hour area under the plasma concentration-time curve (AUC(0-24)) for both ethinyl estradiol (mean 24%, 95% confidence interval [CI] 18%, 31%) and norethindrone (mean 13%, 95% CI 8%, 18%) as compared with treatment with OC-placebo. Ethinyl estradiol maximum plasma concentration (C(max)) was slightly (mean 8%, 95% CI 2%, 15%) though statistically significantly higher for OC-fluconazole treatment as compared with OC-placebo treatment. Norethindrone C(max) was not different (95% CI -6%, 11%) between the two treatment groups. No adverse events related to treatment were seen in the fluconazole treatment group. CONCLUSION: The concomitant administration of 300 mg fluconazole once weekly, twice the recommended dose for vaginal candidiasis, to women using OCs results in a slight increase in OC concentrations. Therefore, it appears that there is no threat of contraceptive failure because of concomitant fluconazole administration.

Pharmacokinetics of ampicillin and sulbactam in pediatric patients.

Intravenous ampicillin-sulbactam is effective in the treatment of various infections in adults, but little is known about the pharmacokinetics (PK) of ampicillin-sulbactam in children. The objective of this study was to determine the PK of ampicillin and sulbactam in pediatric patients with intra-abdominal infection, skin and/or skin structure infection, or periorbital-preseptal and facial cellulitis. Intravenous ampicillin and sulbactam (2:1), 40 to 80 mg/kg of body weight, were given every 6 h for 2 to 6 days to 28 pediatric patients. The ages ranged from 1 to 6 years for 10 patients, 6.1 to 10 years for 9 patients, and 10.1 to 12 years for 9 patients. Multiple blood samples were obtained and analyzed for ampicillin and sulbactam in plasma and serum by high-performance liquid chromatography. The mean maximum concentration of drug in serum ranged from 177 to 200 micrograms/ml for ampicillin and 82 to 102 micrograms/ml for sulbactam in the three age groups. The mean total clearance, steady-state distribution volume, and half-life were 4.76 ml/min/kg, 0.32 liter/kg, and 0.77 h, respectively, for ampicillin and 4.95 ml/min/kg, 0.34 liter/kg, and 0.81 h, respectively, for sulbactam. Dose or gender did not affect the PK of ampicillin or sulbactam. The PK of ampicillin and sulbactam in these patients were comparable to those reported in adults. The combination was well tolerated in pediatric patients.

Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine.

The pharmacokinetic interactions of sertraline and fluoxetine with the tricyclic antidepressant desipramine were studied in 18 healthy male volunteers phenotyped as extensive metabolizers of dextromethorphan. Concentrations in plasma were determined after 7 days of desipramine (50 mg/day) dosing alone, during the 21 days of desipramine and selective serotonin reuptake inhibitor (SSRI) coadministration (fluoxetine, 20 mg/day; sertraline, 50 mg/day), and for 21 days of continued desipramine administration after SSRI discontinuation. Desipramine Cmax was increased 4.0-fold versus 31% and AUC0-24 was increased 4.8-fold versus 23% for fluoxetine versus sertraline, respectively, relative to baseline after 3 weeks of coadministration. Desipramine trough concentrations approached baseline within 1 week of sertraline discontinuation but remained elevated for the 3-week follow-up period after fluoxetine discontinuation. Concentrations of SSRIs and their metabolites correlated significantly with desipramine concentration changes (for fluoxetine/norfluoxetine, r = 0.94 to 0.96; p < 0.001; for sertraline/desmethylsertraline, r = 0.63; p < 0.01). Thus, sertraline had less pharmacokinetic interaction with desipramine than did fluoxetine at their respective, minimum, usually effective doses.