Desvenlafaxine

Drug Levels and Effects:




Summary of Use during Lactation:


Modest doses of desvenlafaxine are excreted into breastmilk, but serum drug levels of breastfed infants are less than 10% of simultaneous maternal levels. Total drug exposure of breastfed infants is about half of that experienced by breastfed infants whose mothers are taking venlafaxine.[1] Breastfed infants, especially newborn or preterm infants, should be monitored for excessive sedation and adequate weight gain if this drug is used during lactation, possibly including measurement of serum levels to rule out toxicity if there is a concern. With the related drug venlafaxine, newborn infants of mothers who took the drug during pregnancy sometimes experienced poor neonatal adaptation as seen with other antidepressants such as SSRIs or SNRIs. Similar effects may occur with desvenlafaxine.


Drug Levels:


Desvenlafaxine (O-desmethylvenlafaxine) is an active metabolite of venlafaxine with similar antidepressant activity.[2]

Maternal Levels.

The average maternal plasma concentration of desvenlafaxine after the usual dose of 100 mg daily is 190 mcg/L in CYP2D6 extensive metabolizers and 250 mcg/L in poor metabolizers.[3] Using the average milk-to-plasma ratio of desvenlafaxine of 2.83 from 2 studies using venlafaxine during breastfeeding,[4][5] the average milk concentration would be expected to be 538 to 708 mcg/L or 81 to 106 mcg/kg daily. An exclusively breastfed infant would receive an estimated 5.7 to 7.4% of the maternal weight-adjusted dosage.

Ten lactating women had been taking desvenlafaxine from 4 to 35 days in doses of 50 to 150 mg daily or an average of 1.2 mg/kg daily (95% CI: 0.93 to 1.5 mg/kg daily). Each woman provided several milk samples over a 24-hour period. Peak milk concentrations occurred at an average of 3.3 hours after the dose. An exclusively breastfed infant in this study would have received an estimated 85 mcg/kg daily or 6.8% (95% CI: 5.5 to 8.1%) of the maternal weight-adjusted dosage.[1]

A nursing mother was taking oral desvenlafaxine 250 mg and amisulpiride 100 mg twice daily. Eight breastmilk samples were obtained over a 24-hour period with a breast pump. The average breastmilk concentration was 1.9 mg/L which equated to an infant dose of 0.29 mg/kg daily or 7.8% of the maternal weight-adjusted dosage.[6]

Infant Levels.

Ten infants were breastfed (8 exclusively) during maternal use of desvenlafaxine in doses of 50 to 150 mg daily or an average of 1.2 mg/kg daily. The infants had an average serum desvenlafaxine level of 16 mcg/L which averaged 4.8% of the simultaneous maternal serum concentration taken at about 6.5 hours after the maternal dose. Considering only the exclusively breastfed infants, infant exposure would have averaged 5.8% of the maternal serum concentration.[1]

A nursing mother was taking oral desvenlafaxine 250 mg and amisulpiride 100 mg twice daily for 12.6 weeks. Her partially breastfed infant was 5 months old. The infant's serum desvenlafaxine concentration 3.1 hours after the mother's daily dose was 13 mcg/L or 1.7% of the maternal serum concentration.[6]


Effects in Breastfed Infants:


Ten infants ranging in age from 0.9 to 12.7 months were breastfed (8 exclusively) during maternal use of desvenlafaxine in doses of 50 to 150 mg daily or an average of 1.2 mg/kg daily. Mothers were also taking lorazepam (n = 6), quetiapine (n = 5), lamotrigine (n = 2), levonorgestrel (n = 2), domperidone (n = 1), andtemazepam(n = 1). Infants were studied after an average of 9 days of exposure (range 4 to 35 days) of desvenlafaxine exposure via breastmilk. At the time of the study, 7 of the 10 infants were at a lower growth percentile than at the time of birth. Examination by a pediatrician found that all infants were healthy and had Denver developmental scores that matched their age on the day of the study.[1]


Possible Effects on Lactation:


In an outpatient study that followed 1395 patients who received long-term desvenlafaxinene therapy, 2 patients developed elevated serum prolactin levels and one developed galactorrhea.[7] The clinical relevance of these findings in nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.


Alternate Drugs to Consider:


Nortriptyline,Paroxetine,Sertraline


References:


1. Rampono J, Teoh S, Hackett LP et al. Estimation of desvenlafaxine transfer into milk and infant exposure during its use in lactating women with postnatal depression. Arch Womens Ment Health. 2011;14:49-53. PMID:20960017
2. Weissman AM, Levy BT, Hartz AJ et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161:1066-78. PMID:15169695
3. Preskorn S, Patroneva A, Silman H et al. Comparison of the pharmacokinetics of venlafaxine extended release and desvenlafaxine in extensive and poor cytochrome P450 2D6 metabolizers. J Clin Psychopharmacol. 2009;29:39-43. PMID:19142106
4. Ilett KF, Kristensen JH, Hackett LP et al. Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants. Br J Clin Pharmacol. 2002;53:17-22. PMID:11849190
5. Ilett KF, Hackett LP, Dusci LJ et al. Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human milk. Br J Clin Pharmacol. 1998;45:459-62. PMID:9643618
6. Ilett KF, Watt F, Hackett LP, Kohan R, Teoh S. Assessment of infant dose through milk in a lactating woman taking amisulpride and desvenlafaxine for treatment-resistant depression. Ther Drug Monit. 2010;32:704-7. PMID:20926994
7. Tourian KA, Pitrosky B, Padmanabhan SK, Rosas GR. A 10-month, open-label evaluation of desvenlafaxine in outpatients with major depressive disorder. Prim Care Companion J Clin Psych. 2011;13. PMID:15303249



Substance Identification:




Substance Name:

Desvenlafaxine

CAS Registry Number:

93413-62-8

Drug Class:


  • Antidepressants

  • Serotonin Uptake Inhibitors

  • Antidepressive Agents, Second-Generation


  • Administrative Information:




    LactMed Record Number:


    698


    Last Revision Date:


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