Paroxetine Pregnancy and Breastfeeding Warnings
Paroxetine Pregnancy Warnings
Animal studies have failed to reveal evidence of teratogenicity when administered during organogenesis in doses up to 8 times the MRHD (based on mg/m2). There are no controlled data in human pregnancy. Epidemiological studies have shown that infants exposed to paroxetine in the first trimester of pregnancy have an increased risk of congenital malformations, particularly cardiovascular malformations. Neonates exposed to paroxetine late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. Infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). This condition has been associated with neonatal morbidity and mortality. Eclampsia has been reported with the use of paroxetine. There have been reports of premature births in pregnant women exposed to paroxetine. According to the manufacturer, women who intend to become pregnant or are in their first trimester of pregnancy should only receive paroxetine if deemed absolutely essential and only after all other treatment options have been considered and ruled out. In addition, when treating pregnant women with paroxetine during the third trimester, the physician should carefully consider both the potential risks and benefits of treatment. Some clinical studies have shown that SSRIs (including paroxetine) may affect sperm quality during SSRI treatment, which may affect fertility in some men. The American College of Obstetricians and Gynecologists Committee on Obstetric Practice recommends avoiding the use of paroxetine in pregnant women and in women planning to become pregnant. A study has reported that paroxetine does not appear to be associated with an increased risk of cardiovascular defects following use in early pregnancy, as the incidence in more than 3,000 infants was well within the population incidence of approximately 1%. Effects to the newborn have been consistent with either a direct toxic effect or a drug discontinuation syndrome. In some cases, the clinical picture has been consistent with serotonin syndrome. One study compared 267 women exposed to a selective serotonin reuptake inhibitor (SSRI), fluvoxamine, paroxetine, or sertraline, to 267 controls. Exposure to SSRIs was not reported to be associated with either increased risk for major malformations, higher rates of miscarriage, stillbirth, or prematurity. Mean birth weights among SSRI users were similar to controls, as were the gestational ages. The study concluded that the SSRIs fluvoxamine, paroxetine, and sertraline did not appear to increase teratogenic risk when used in their recommended doses. A study based on the Swedish national registry data evaluated infants of women (n=5123) exposed to antidepressants in early pregnancy including paroxetine (n=815). The study reported an increased risk of cardiovascular malformations (primarily ventricular and atrial septal defects) in infants exposed to paroxetine in early pregnancy compared to the entire registry population. The rate of cardiac defects was 2% for infants exposed to paroxetine early in pregnancy versus 1% for the entire registry population. There is no increase in overall risk of congenital malformations in the same group of paroxetine- exposed infants. A retrospective cohort study based on U.S. United Healthcare data reported a trend towards increased risk for cardiovascular malformations in infants of mothers dispensed paroxetine (n = 5956) compared to infants of mothers dispensed other antidepressants (n = 815) during the first trimester. In the infants whose mothers received paroxetine and developed cardiovascular defects, 9 out of 12 had ventricular septal defects. In addition, this study suggested increased risk of overall major congenital malformations (inclusive of the cardiovascular defects) for infants whose mothers received paroxetine during the first trimester compared to other antidepressants. The incidence of all congenital malformations following first trimester exposure was 4% for paroxetine and 2% for other antidepressants. According to the results of a literature review, exposure to paroxetine late in pregnancy seems to be more frequently associated with neonatal withdrawal syndrome including symptoms of respiratory depression, poor feeding, lethargy, and jitteriness, than other SSRIs. In addition, the author indicates that paroxetine use early in pregnancy appears to be associated with an increased risk for congenital and cardiac malformations. The results of a cohort study indicate that 30% of neonates who had prolonged exposure to SSRIs in utero experience symptoms, in a dose response manner, of a neonatal abstinence syndrome (e.g., tremor, gastrointestinal or sleep disturbances, hypertonicity, high pitched cry) after birth. The authors suggest that infants exposed to SSRIs should be closely monitored for a minimum of 48 hours after birth. There are postmarketing reports of premature births in pregnant women exposed to paroxetine and other SSRIs. The effect of paroxetine on labor and delivery in humans is unknown. Women should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy. There is an increased risk for persistent pulmonary hypertension of the newborn (PPHN) in infants exposed to SSRIs late in pregnancy. A case controlled study reported a 6 fold increase in risk for developing PPHN for infants exposed to SSRIs after the 20th week of gestation when compared to infants who had not been exposed to antidepressants during pregnancy. PPHN occurs in approximately 1 to 2 per 1000 live births in the general population. FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. FDA pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.
FDA pregnancy category (for paroxetine): D FDA pregnancy category (for paroxetine marketed under the trade name Brisdelle [R]): X Use of paroxetine is not recommended unless the benefit outweighs the risk to the fetus Use of paroxetine marketed under the trade name Brisdelle [R]) is contraindicated because menopausal vasomotor symptoms (VMS) do not occur during pregnancy and paroxetine can cause fetal harm. Women of childbearing potential should be encouraged to use an adequate form of birth control.
Paroxetine Breastfeeding Warnings
Caution is recommended when paroxetine is administered to nursing women. For paroxetine marketed under the trade name Brisdelle (R), the manufacturer recommends discontinuing nursing or discontinuing the drug, taking into account the importance of the drug to the mother. (Since Brisdelle (R) is only indicated for treatment of menopause, there is no use in nursing women). Excreted into human milk: Yes Excreted into animal milk: Yes Paroxetine has the potential for serious adverse reactions in nursing infants.
One study involving 23 breast-feeding mothers on paroxetine found detectable levels of paroxetine present in all maternal samples and in 24 of 25 breast milk samples. However, in all of the infant serum samples, the paroxetine concentrations were below the lower limit of quantification. Furthermore, no unusual effects were reported in any of the infants. Another study has reported that the relative dose to a suckling infant for paroxetine is lower than that reported for fluoxetine or citalopram and higher than that reported for sertraline or fluvoxamine. One case study has reported breast milk levels of paroxetine to be nondetectable over a 24 hour collection, including foremilk and hindmilk samples, and the serum level of paroxetine was also reported as nondetectable.
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