Difference between revisions of "Combining-Lamotrigine-Valproic acid"
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* This combination of drugs may have possible synergistic effects. However, the pharmacokinetic drug interactions will influence the plasma levels. Dose adaptation will be recommended for this combination. | * This combination of drugs may have possible synergistic effects. However, the pharmacokinetic drug interactions will influence the plasma levels. Dose adaptation will be recommended for this combination. | ||
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* Valproate can increase lamotrigine plasma levels significantly by inhibiting lamotrigine’s glucuronidation. This effect of valproate is dose-dependent.<ref name=”bazire”> Bazire S, Psychotropic Drug Directory 2007, HealthComm UK Limited, Aberdeen, 2007. </ref> | * Valproate can increase lamotrigine plasma levels significantly by inhibiting lamotrigine’s glucuronidation. This effect of valproate is dose-dependent.<ref name=”bazire”> Bazire S, Psychotropic Drug Directory 2007, HealthComm UK Limited, Aberdeen, 2007. </ref> | ||
− | * Very slow titration of lamotrigine is recommended because reports of lamotrigine-related skin rashes. <ref> {{Pubmed|16225978|Chang CC at al, Toxic epidermal necrolysis with combination lamotrigine and valproate in bipolar disorder. Prog | + | * Very slow titration of lamotrigine is recommended because reports of lamotrigine-related skin rashes. <ref> {{Pubmed|16225978|Chang CC at al, Toxic epidermal necrolysis with combination lamotrigine and valproate in bipolar disorder. Prog Neuropsych. Biol Psychiatry. 2006 Jan;30(1):147-50}}</ref> |
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Adding valproic acid to lamotrigine.
- Lamotrigine is principally metabolised by UDP-glucuronosyltransferases.
- Valproic acid is principally metabolized by CYP2C9, CYP2C19, CYP2A6 and UDP-glucuronosyltransferases. Valproic acid is an inhibitor of the enzymes CYP2C9, epoxide-hydroxylase and UDP-glucuronosyltransferases.
- This combination of drugs may have possible synergistic effects. However, the pharmacokinetic drug interactions will influence the plasma levels. Dose adaptation will be recommended for this combination.
- Reduce the lamotrigine dose by 50% of the general dose when combined with valproate. Start valproate at low dose and increase dose based on serum concentration slowly. [5] [6]
- Valproate can increase lamotrigine plasma levels significantly by inhibiting lamotrigine’s glucuronidation. This effect of valproate is dose-dependent.[7]
- Very slow titration of lamotrigine is recommended because reports of lamotrigine-related skin rashes. [8]
- ↑ 1.0 1.1 Farmacotherapeutisch Kompas; Toxicologie (dutch)
- ↑ 2.0 2.1 Farmacotherapeutisch Kompas - lamotrigine (dutch)
Cite error: Invalid
<ref>
tag; name "ftk" defined multiple times with different content - ↑ Drugs.com lamotrigine
- ↑ KNMP; Informatorium Medicamentorum 2023; Monografie "valproaat" (Dutch)
- ↑ Schalekamp T. et al, Interacties met Psychofarmaca, Stichting Health Base, Houten, 2002.
- ↑ Pisani at al, Interaction of lamotrigine with sodium valproate. Lancet. 1993 May 8;341(8854):1224.
- ↑ Bazire S, Psychotropic Drug Directory 2007, HealthComm UK Limited, Aberdeen, 2007.
- ↑ Chang CC at al, Toxic epidermal necrolysis with combination lamotrigine and valproate in bipolar disorder. Prog Neuropsych. Biol Psychiatry. 2006 Jan;30(1):147-50
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