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Historical Information on Paroxetine hydrochloride (marketed as Paxil)
7/2006: The issues described below have been addressed in product labeling. Increase in the Risk of Birth Defects: [Issued 12/2005] Preliminary results of two recent studies indicate that paroxetine increases the risk of congenital malformations, particularly cardiovascular malformations. Based on the new data, paroxetine’s pregnancy category is being changed from C to D. Patients taking paroxetine who become pregnant or who are currently in their first trimester of pregnancy should be alerted to the potential risk to the fetus. Discontinuing paroxetine therapy or switching to another antidepressant should be considered for these patients. For individual patients, however, the benefits of continuing paroxetine may outweigh the potential risk to the fetus. Paroxetine should generally not be initiated in women who are in their first trimester of pregnancy or in women who plan to become pregnant. The FDA is currently awaiting the final results of the recent studies and accruing additional data pertaining to the use of paroxetine in pregnancy in order to better characterize the risk of paroxetine. The FDA will update this sheet as new information becomes available. This information reflects FDA’s preliminary analysis of data concerning this drug. FDA is considering, but has not reached a final conclusion about this information. FDA intends to update this sheet when additional information or analyses become available. Recommendations See above Data Summary Preliminary analyses from two recent unpublished epidemiological studies have shown that paroxetine use in the first trimester of pregnancy is associated with an increased risk of specific types of congenital malformations. In a study based on Swedish national registry data, infants exposed to paroxetine in early pregnancy had an approximately two-fold increased risk for cardiac defects compared to the entire national registry population, about 2% in paroxetine-exposed infants vs. 1% in the total population. The majority of cardiac defects in paroxetine-exposed infants were atrial and ventricular septal defects. In a separate study using a United States (U.S.) insurance claims database, infants of women who received paroxetine in the first trimester had a 1.5-fold increased risk of cardiovascular malformations compared to infants of women who received other antidepressants in the first trimester, 1.5% in the paroxetine-exposed infants vs. 1% in infants exposed to other antidepressants. The majority of the cardiovascular defects observed in this study were ventricular septal defects. Exposure to paroxetine in the first trimester was also associated with an approximately two-fold higher risk for overall congenital malformations (including cardiovascular malformations) compared to exposure to other antidepressants in the first trimester, about 4% vs. 2% prevalence of all congenital malformations. Separate analyses were not done for any specific malformations other than cardiovascular malformations. The FDA is in the process of accruing additional data to better characterize the risk of paroxetine. Suicidality in Pediatric and Adult Patients [Issued 7/2005] All patients being treated with any type of antidepressants should be observed closely for clinical worsening and suicidality especially during the first few months of therapy and when the dose is modified. Pediatrics FDA has concluded that suicidal thinking or behavior may increase in pediatric patients treated with any type of antidepressant, especially early in treatment. Increases in suicidal thinking or behavior due to drug can be expected in about 1 out of 50 treated pediatric patients. Note that, although paroxetine is prescribed for pediatric patients, it is not approved by FDA for use in pediatric patients. Adults Several recent scientific publications report the possibility of an increased risk for suicidal behavior in adults who are being treated with antidepressant medications. Even before these reports became available, FDA began a complete review of all available data to determine whether there is an increased risk of suicidality (suicidal thinking or behavior) in adults being treated with any type of antidepressant medication. It is expected that this review will require a year or longer to complete. In the meantime, FDA is highlighting that adults being treated with any type of antidepressant medication, particularly those being treated for depression, should be watched closely for worsening of depression and for increased suicidal thinking or behavior. This information reflects FDA’s preliminary analysis of data concerning this drug. FDA is considering, but has not reached a final conclusion about this information. FDA intends to update this sheet when additional information or analyses become available. Recommendations All patients being treated with any type of antidepressant for any indication should be observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. For pediatric patients, such observation would generally include at least weekly face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks. Additional contact by telephone may be appropriate between face-to-face visits. Adults whose symptoms worsen while being treated with antidepressant medications, including an increase in suicidal thinking or behavior, should be evaluated by their healthcare professional. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Data Summary Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4 percent, twice the placebo risk of 2 percent. No suicides occurred in these trials; however, the duration of treatment was limited. Spontaneous post-marketing reports of suicide-related events associated with the use of SSRIs, including suicidal ideation, suicide attempt, self-mutilation and completed suicide have been received. Because these events may also be related to underlying psychiatric illness, definitive evaluation of the effects of SSRIs on suicide related events from post-marketing reports alone is not possible, and the data from controlled clinical trials is more informative. Although there are no similar comprehensive data linking the use of antidepressant medications and an increased risk of suicidality in adults, FDA has initiated a complete review of all available data. FDA has asked the manufacturers of all marketed antidepressants to identify all placebo-controlled clinical trials conducted in adults in their development programs for their antidepressant products, regardless of the indication studied, and to provide information from these trials to FDA. Manufacturers are being asked to use a similar approach to assembling this information as was used in evaluating the risk of suicidality in placebo-controlled trials in pediatric patients treated with antidepressant medications. Other Information
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Date created: July 19, 2006 |
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