JohnBoy2000
Bluelighter
- Joined
- May 11, 2016
- Messages
- 2,465
SSRI's supposedly all interact with CYP2D6, which is responsible for metabolism of many psychoactive drugs - thioridazine, several AP's, etc.
Lexapro seemingly has the lowest interaction potential of any SSRI.
Anyone have experience with the degree to which it may actually interact with other drugs?
Have you found dose adjustment of the combination agent being necessary?
Doesn't seem to be too much information as to interaction potential on it - but it is noted that it mildly inhibits CYP2D6 in literature.
Also - what is referred to as "clinically significant" in literature, I believe refers to implication of plasma levels to below 30%, which, in my opinion, is actually significant enough.
Leaving this here - for later review; from FDA pages on Lexapro and Effexor:
Imipramine - Venlafaxine did not affect the pharmacokinetics of imipramine and2-OH-imipramine. However, desipramine AUC, Cmax, and Cmin increased by about 35% in thepresence of venlafaxine. The 2-OH-desipramine AUC?s increased by at least 2.5 fold (withvenlafaxine 37.5 mg q12h) and by 4.5 fold (with venlafaxine 75 mg q12h). Imipramine did notaffect the pharmacokinetics of venlafaxine and ODV. The clinical significance of elevated2-OH-desipramine levels is unknown.
*****
Drugs Metabolized by Cytochrome P4502D6 - In vitro studies did not reveal an inhibitory effect of escitalopramon CYP2D6. In addition, steady state levels of racemic citalopram were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram, suggestingthat coadministration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significanteffects on escitalopram metabolism.
However, there are limited in vivo data suggesting a modest CYP2D6inhibitory effect for escitalopram, i.e., coadministration of escitalopram (20 mg/day for 21 days) with the tricyclicantidepressant desipramine (single dose of 50 mg), a substrate for CYP2D6, resulted in a 40% increase in Cmax anda 100% increase in AUC of desipramine. The clinical significance of this finding is unknown. Nevertheless,caution is indicated in the coadministration of escitalopram and drugs metabolized by CYP2D6.
Metoprolol - Administration of 20 mg/day LEXAPRO for 21 days in healthy volunteers resulted in a 50%increase in Cmax and 82% increase in AUC of the beta-adrenergic blocker metoprolol (given in a single dose of 100mg). Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministrationof LEXAPRO and metoprolol had no clinically significant effects on blood pressure or heart rate.
**
In a controlled study of healthy male volunteers, multiple doses
of citalopram 40 mg significantly increased single- dose desipramine plasma levels (50% rise
in desipramine AUC).
Lexapro seemingly has the lowest interaction potential of any SSRI.
Anyone have experience with the degree to which it may actually interact with other drugs?
Have you found dose adjustment of the combination agent being necessary?
Doesn't seem to be too much information as to interaction potential on it - but it is noted that it mildly inhibits CYP2D6 in literature.
Also - what is referred to as "clinically significant" in literature, I believe refers to implication of plasma levels to below 30%, which, in my opinion, is actually significant enough.
Leaving this here - for later review; from FDA pages on Lexapro and Effexor:
Imipramine - Venlafaxine did not affect the pharmacokinetics of imipramine and2-OH-imipramine. However, desipramine AUC, Cmax, and Cmin increased by about 35% in thepresence of venlafaxine. The 2-OH-desipramine AUC?s increased by at least 2.5 fold (withvenlafaxine 37.5 mg q12h) and by 4.5 fold (with venlafaxine 75 mg q12h). Imipramine did notaffect the pharmacokinetics of venlafaxine and ODV. The clinical significance of elevated2-OH-desipramine levels is unknown.
*****
Drugs Metabolized by Cytochrome P4502D6 - In vitro studies did not reveal an inhibitory effect of escitalopramon CYP2D6. In addition, steady state levels of racemic citalopram were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram, suggestingthat coadministration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significanteffects on escitalopram metabolism.
However, there are limited in vivo data suggesting a modest CYP2D6inhibitory effect for escitalopram, i.e., coadministration of escitalopram (20 mg/day for 21 days) with the tricyclicantidepressant desipramine (single dose of 50 mg), a substrate for CYP2D6, resulted in a 40% increase in Cmax anda 100% increase in AUC of desipramine. The clinical significance of this finding is unknown. Nevertheless,caution is indicated in the coadministration of escitalopram and drugs metabolized by CYP2D6.
Metoprolol - Administration of 20 mg/day LEXAPRO for 21 days in healthy volunteers resulted in a 50%increase in Cmax and 82% increase in AUC of the beta-adrenergic blocker metoprolol (given in a single dose of 100mg). Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministrationof LEXAPRO and metoprolol had no clinically significant effects on blood pressure or heart rate.
**
In a controlled study of healthy male volunteers, multiple doses
of citalopram 40 mg significantly increased single- dose desipramine plasma levels (50% rise
in desipramine AUC).
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