Information on level of drugs into breastmilk
Wendy Jones in Breastfeeding and Medication, 2013
the serum of four babies. No adverse events were noted and all babies reached their developmental milestones. She deduced a m/p ratio of 1.93 for sertraline and 1.64 for the metabolite N-desmethylsertraline. Stowe et al. (2003) studied 26 women taking 25 to 200 mg sertraline daily, fifteen of whom supplied breastmilk samples. He found widely varying milk plasma ratios 0.42 to 4.81 and that maternal daily dose, duration of medication exposure, and infant age and weight at sampling did not correlate with either detectability. No adverse events were documented. There are multiple published studies on infants with no untoward effects noted. In almost all cases little, if any, of the drug has been detected in the infant plasma. There is one report of an infant developing benign neonatal sleep at 4 months, which resolved at 6 months. It is unclear whether this bears any relationship with the maternal use of sertraline (Mammen et al. 1997). Rohan (1997) reported a case of agitation which resolved spontaneously. Relative infant dose quoted as 0.4 to 2.2% (Hale 2012 online access). The BNF states that it is not known to be harmful but consider discontinuing breastfeeding. Compatible with use during breastfeeding and anti-depressant of choice during breastfeeding because it is highly plasma protein bound and has an inactive metabolite.
Information on level of drugs into breastmilk
Wendy Jones in Breastfeeding and Medication, 2018
Hendrick et al. (2001) studied 30 mothers and babies and found detectable levels in 24% of samples. This was more likely with younger babies and those exposed to 100 mg or more daily. They noted no adverse events. Kristensen et al. (1998) studied eight women and their babies (average age 5.7 months) and could not detect any drug in the serum of four babies. No adverse events were noted and all babies reached their developmental milestones. She deduced a m/p ratio of 1.93 for sertraline and 1.64 for the metabolite N-desmethylsertraline. Stowe et al. (2003) studied 26 women taking 25–200 mg sertraline daily, 15 of whom supplied breastmilk samples. They found widely varying m/p ratios of 0.42–4.81 and that maternal daily dose, duration of medication exposure, and infant age and weight at sampling did not correlate with either detectability. No adverse events were documented. There are multiple published studies on infants with no untoward effects noted. In almost all cases little, if any, of the drug has been detected in the infant plasma. There is one report of an infant developing benign neonatal sleep at 4 months, which resolved at 6 months. It is unclear whether this bears any relationship with the maternal use of sertraline (Mammen et al. 1997). Rohan (1997) reported a case of agitation that resolved spontaneously. Relative infant dose quoted as 0.4–2.2% (Hale 2017 online access).
Inhibitors of Human CYP2D6
Shufeng Zhou in Cytochrome P450 2D6, 2018
Most SSRIs are reversible CYP2D6 inhibitors (Figure 4.3) (Ball et al. 1997; Crewe et al. 1992; Otton et al. 1996). Fluoxetine inhibits CYP2D6 with a Ki of 0.2 μM (Otton et al. 1993). Otton et al. (1996) have compared the inhibitory potency of several SSRIs for CYP2D6-catalyzed dextromethorphan O-demethylation. The authors have found that paroxetine, fluoxetine, norfluoxetine, fluvoxamine, and sertraline are potent inhibitors of CYP2D6-catalyzed dextromethorphan O-demethylation with Ki values of 0.065 to 1.8 μM (Otton et al. 1996). Citalopram and duloxetine inhibit CYP2D6 with a Ki of 19 and 4.5 μM, respectively. Venlafaxine, R-(+)-venlafaxine, and S-(–)-venlafaxine cause less potent inhibition for CYP2D6, with Ki values of 33, 52, and 22 μM, respectively (Otton et al. 1996). Venlafaxine does not inhibit CYP1A2 and 2C9. Consistently, fluoxetine, paroxetine, fluvoxamine, and sertraline are found to be inhibitors of CYP2D6-mediated imipramine 2-hydroxylation, with Ki values of 1.6, 3.2, 8.0, and 24.7 μM, respectively (Ball et al. 1997). Fluoxetine and norfluoxetine also significantly inhibit desipramine 2-hydroxylation with Ki values of 3.0 and 3.5 μM, respectively, while sertraline and its metabolite desmethylsertraline inhibit the reaction with Ki of 22.7 and 16.0 μM, respectively (von Moltke et al. 1994). Venlafaxine is a less potent inhibitor of imipramine 2-hydroxylation with a Ki of 41.0 μM.
Using sertraline in postpartum and breastfeeding: balancing risks and benefits
Published in Expert Opinion on Drug Safety, 2018
Alessandro Cuomo, Giuseppe Maina, Stephen M Neal, Graziella De Montis, Gianluca Rosso, Simona Scheggi, Bruno Beccarini Crescenzi, Simone Bolognesi, Arianna Goracci, Anna Coluccia, Fabio Ferretti, Andrea Fagiolini
Pinheiro and colleagues [41] conducted a review and meta-analysis [41] to evaluate the risks and benefits of sertraline during breastfeeding. The authors did not find a significant correlation between infant and maternal sertraline plasma levels, owing to the low to non-detectable infant plasma concentrations, which were not affected by maternal sertraline levels. A significant relationship was instead found between infant and maternal plasma concentrations of desmethylsertraline. However, desmethylsertraline is not as active as sertraline.
Dasotraline in ADHD: novel or me too drug?
Published in Expert Review of Neurotherapeutics, 2019
Pankhuree Vandana, Eugene Arnold
Structurally, dasotraline is a stereoisomer of desmethylsertraline, an active metabolite of sertraline which is a serotonin NE and DA reuptake inhibitor. However, Positron-emission tomographic scan studies have demonstrated weak inhibition of the serotonin transporters at therapeutic dosages of dasotraline [9].
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