Paroxetine Pregnancy and Breastfeeding Warnings
Paroxetine Pregnancy Warnings
Animal studies have failed to reveal evidence of teratogenicity; however, pre- and postimplantation losses and decreased postnatal survival occurred at maternotoxic doses. There are no controlled data in human pregnancy. Some epidemiological studies suggest that the use of paroxetine during the first trimester of pregnancy may be associated with an increased risk of congenital malformations, particularly cardiovascular malformations. The mechanism is unknown. A retrospective epidemiological study involving pregnant women (n=3,581) exposed to paroxetine or other antidepressants during the first trimester suggested an increased risk of overall major congenital and cardiovascular malformations for paroxetine. In this study, 10 out of 14 infants with cardiovascular malformations had ventricular septal defects. The odds ratios for major congenital and cardiovascular malformations for paroxetine compared to other antidepressants were 2.2 and 2.08, respectively. Women exposed to both antidepressants and teratogenic drugs were excluded from these figures. A separate study reported no increased risk for overall major malformations in infants (n=708) born to mothers exposed to paroxetine in early pregnancy. 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 was no reported increase in overall risk of congenital malformations in the same group of paroxetine-exposed infants. A retrospective cohort study based on United Healthcare data from the United States 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. Use of sertraline during pregnancy has been reported to cause symptoms compatible with withdrawal reactions in neonates whose mothers had taken sertraline. Neonates exposed to SSRIs and SNRIs late in the third trimester have uncommonly reported clinical findings including respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These effects have mostly occurred either at birth or within a few days of birth. These features are consistent with either a direct toxic effect of SSRIs and SNRIs, or possibly a drug discontinuation syndrome; in some cases, the clinical picture is consistent with serotonin syndrome. 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 after birth. The authors suggest that infants exposed to SSRIs should be closely monitored for a minimum of 48 hours after birth. Epidemiological data have suggested that the use of SSRIs, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn. 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. Animal data with paroxetine have shown an effect on sperm quality. Human case reports from some SSRIs have shown an effect on sperm quality that is reversible. As yet, the impact of this on human fertility has not been observed. There are postmarketing reports of premature births in pregnant women exposed to paroxetine and other SSRIs; however, a causal relationship has not been established. The effect of paroxetine on labor and delivery in humans is unknown. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US 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 this drug in pregnant women despite potential risks. US 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.
This drug should be avoided during pregnancy; it should only be used if the potential benefit outweighs the potential risk to the fetus, taking into account the risks of untreated depression. US: Brisdelle (R): Use is contraindicated; menopausal vasomotor symptoms (VMS) do not occur during pregnancy and paroxetine can cause fetal harm AU TGA pregnancy category: D US FDA pregnancy category: D US FDA pregnancy category (Brisdelle (R)): X Comments: -Women should be advised to notify their doctor if they become pregnant or intent to become pregnant during therapy. -Abrupt discontinuation should be avoided during pregnancy.
Paroxetine Breastfeeding Warnings
Benefit should outweigh risk; use with caution. Excreted into human milk: Yes Comments: -This drug has been considered one of the preferred antidepressants during breastfeeding. -Mild side effects have been occasionally reported, particularly in infants whose mothers took paroxetine during the third trimester of pregnancy. -Mothers taking an SSRI during pregnancy and postpartum may have difficulty breastfeeding and may require additional breastfeeding support.
Low-dose paroxetine marketed under the name Brisdelle (R) is only indicated for the treatment of menopause and would not be expected to be used in breastfeeding women. The manufacturer of this product recommends discontinuing nursing or discontinuing the drug, taking into the account the importance of the drug to the mother. Data from a pooled analysis of serum levels from published studies and 3 unpublished cases involving 50 mothers taking an average paroxetine daily dose of 21 mg estimated that an exclusively breastfed infant would receive approximately 1.2% of the maternal weight-adjusted dosage of paroxetine. Authors of a pooled analysis of 40 mother-infant pairs from published and unpublished cases found no measurable paroxetine plasma levels in the infants. Sixteen breastfed infants (2 were about 50% breastfed and the others 95% or more breastfed) aged 6 to 13 weeks had undetectable levels of paroxetine (less than 1 mcg/L) during maternal therapy with an average daily paroxetine dose of 18.75 mg. In a controlled cohort study of mothers who took paroxetine during pregnancy there were 36 mothers who took paroxetine during the third trimester and breastfed their infants. Of the 36 mothers, 8 reported side effects in their infants, including alertness, constipation, sleepiness, and irritability. There were no reports of side effects in the control group. No data are available on the contribution of transplacental and breast milk acquisition of the drug. Another study comparing the infants of mothers who took an SSRI during pregnancy for major depression with those of mothers who did not take an SSRI showed mental development and most motor development as being normal at follow-up after about 12.9 months in both groups. Four of the treated mothers took paroxetine at an average daily dose of 28.6 mg for an average of 7.8 months while breastfeeding their infants. Psychomotor development was slightly delayed compared to controls; however, the extent to which breastfeeding contributed to abnormal development could not be determined.
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