- FDA adds boxed warning to Plavix label regarding possible reduced efficacy in certain patients
- FDA approves five-day dosing regimen of Eisai's Dacogen for MDS
- FDA approves Watson's six-month Trelstar formulation for palliative treatment of advanced prostate cancer
- Abbott submits sNDA for new formulation of Lupron Depot in advanced prostate cancer
- FDA grants 510(k) clearance to Fenwal to market Amicus blood cell separator for platelet-related use
- Private FFS MA plans may be linked with higher costs for beneficiaries, GAO report shows
- Pediatric subspecialty telephone consultations may be cost-saving for Medicaid, research reveals
- Use of mental health services greater in health plans with parity in cost sharing, data find
- Public opinions appear split on health care affordability, satisfaction, survey finds
- In Brief: California Supreme Court
Paroxetine interferes with clinical benefit of tamoxifen therapy, research indicates
What's This?
Women with breast cancer who take paroxetine hydrochloride, a selective serotonin uptake inhibitor (SSRI) antidepressant, concomitantly with tamoxifen, a selective estrogen receptor modulator, appear to be more likely to die from the disease than are women who take other SSRIs, according to recently published study results. Cytochrome P450 isoenzyme 2D6 (CYP2D6) is the primary catalyst that converts the prodrug tamoxifen to the active metabolite endoxifen, which has an affinity for the...
Women with breast cancer who take paroxetine hydrochloride, a selective serotonin uptake inhibitor (SSRI) antidepressant, concomitantly with tamoxifen, a selective estrogen receptor modulator, appear to be more likely to die from the disease than are women who take other SSRIs, according to recently published study results.
Cytochrome P450 isoenzyme 2D6 (CYP2D6) is the primary catalyst that converts the prodrug tamoxifen to the active metabolite endoxifen, which has an affinity for the estrogen receptor that is 100 times greater than the parent compound, the authors explained. While SSRIs inhibit CYP2D6 to varying degrees, paroxetine is a particularly potent inhibitor of CYP2D6, they added.
To test the effect of different SSRIs on tamoxifen's efficacy, the investigators conducted a retrospective, population-based cohort study among 2,430 women (aged >=66 years) who were treated with tamoxifen between Jan. 1, 1993, and Dec. 31, 2005, and had overlapping treatment with a single SSRI. The primary endpoint was risk of death from breast cancer after completing tamoxifen treatment. Cox proportional hazard regression was used to examine the effect of SSRI co-prescribing on survival.
The SSRIs analyzed in the study include paroxetine, fluoxetine hydrochloride, sertraline hydrochloride, citalopram hydrobromide, and fluvoxamine maleate. The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride was also included.
After adjusting for potential confounders, including age and duration of tamoxifen treatment, an absolute increase of 25% in the proportion of time on tamoxifen with overlapping paroxetine was associated with a 24% percent increase in the risk of death from breast cancer (P<.05). Absolute increases of 50% and 75% in the proportion of time on tamoxifen with overlapping paroxetine were associated with increases of 54% and 91% in the risk of death from breast cancer (P<.05 for both).
No such risk was observed with the other antidepressants assessed in the study.
The investigators estimated that the use of paroxetine for 41% of the time on tamoxifen treatment (the median overlap in the study) would result in 1 additional breast cancer death within 5 years of ending tamoxifen treatment for every 19.7 patients thus treated (95% CI, 12.5-46.3).
When the analysis was extended to include death from any cause, the use of paroxetine was again associated with an increased risk of death; however, as in the original analysis, no such increase in the risk of death was seen with the other antidepressants in the study.
"When co-prescription of tamoxifen with an antidepressant is necessary, preference should be given to antidepressants that show little or no inhibition of CYP2D6," the authors concluded. (Kelly CM, et al. BMJ 2010;340;c693.)
Data indicate potential favorable long-term effect of childbirth on MS course 
What's This?
Among women with multiple sclerosis (MS), those who have children--particularly those who have children after MS onset--seem to experience a more benign disease course relative to women who do not give birth, study results indicate.Researchers evaluated the long-term effects of childbirth in 330 women with MS; the mean duration of MS was 17.7 years, and 55% of the women had an Expanded Disability Status Scale (EDSS) score of >=6. Of these women, 80 had no children, 170 had...
BRCA status, age at first breast cancer affects risk of developing contralateral breast cancer, study shows
What's This?
Women with unilateral breast cancer who carry a BRCA1 mutation and who had their breast cancer at a younger age have a greater risk of developing contralateral breast cancer than do women who carry the BRCA2 mutation or develop initial breast cancer at an older age, according to recently published study results.If women carry a deleterious BRCA1 or BRCA2 mutation, they not only have a higher risk of breast and ovarian cancer, but they also have a greater risk of developing a...
National database shows marginal increase in risk of intrauterine growth restriction, cesarean delivery among pregnant women with MS, epilepsy, no increase in risk of other adverse outcomes
What's This?
Pregnant women with multiple sclerosis (MS) or epilepsy seem to have an increased risk of intrauterine growth restriction (IUGR) and cesarean delivery relative to the general obstetric population, according to an analysis of a large U.S. database. However, the database did not show an increased risk of other adverse pregnancy outcomes, such as preeclampsia and premature rupture of membranes (PROM).Researchers at Stanford University...
Registry data reveal no major teratogenicity signal associated with sumatriptan use during pregnancy
What's This?
A new analysis of data from the Sumatriptan and Naratriptan Pregnancy Registry has not shown any signal for major teratogenicity associated with sumatriptan exposure during pregnancy. Although the authors of the analysis suggest that these findings offer some level of reassurance regarding the safety of in utero exposure to the drug, they caution that the registry size is too small to draw definitive conclusions or to evaluate the risk of specific defects.The Sumatriptan and...
- Diabetes associated with increased risk of perinatal depression in low-income mothers, Medicaid data show
- Metabolic syndrome associated with increased risk of developing cognitive impairment, results indicate
- Researchers evaluate predictors of re-excision, residual disease in women with close, positive margins following partial mastectomy
- Metabolic syndrome risk rises with increased testosterone levels during menopause, new data suggest
- Among pregnant women, those with migraine have increased risk of vascular events, findings show
- Preeclampsia associated with epilepsy in offspring, data show
- Postmenopausal women who take raloxifene for osteoporosis appear to experience improved spine, hip BMD with addition of PTH, data suggest
- Metabolic syndrome risk rises with increased testosterone levels during menopause, new data suggest
- Prenatal exposure to sodium valproate linked to greater autism spectrum disorder risk, according to early results
- ASCO publishes new guidelines for use of tumor marker tests to diagnose, manage breast cancer
