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Drug Interactions between Depakote and Lamictal

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

lamoTRIgine divalproex sodium

Applies to: Lamictal (lamotrigine) and Depakote (divalproex sodium)

ADJUST DOSE: Coadministration with valproic acid has been shown to significantly increase the plasma concentrations of lamotrigine and the risk of potentially serious and life-threatening rash induced by lamotrigine, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Severe, disabling tremors and ataxia have also been reported. The mechanism is competitive inhibition of lamotrigine glucuronidation by valproic acid. Pharmacokinetic data indicate that valproic acid can more than double the elimination half-life of lamotrigine, whether given with or without enzyme-inducing antiepileptic drugs (EIAEDs) such as carbamazepine, phenytoin, and phenobarbital. In a study of eight patients treated with lamotrigine, half of whom also received EIAEDs, valproic acid 200 mg/day and 1000 mg/day (each for 3 weeks) increased the dose-corrected area under the plasma concentration-time curve (AUC) of lamotrigine by an average of 84% and 160%, respectively. Corresponding lamotrigine half-life increased by an average of 37% and 150%. Additive or synergistic pharmacodynamic effects may also contribute to the interaction, which some investigators suggest is responsible in some patients for enhanced antiepileptic efficacy beyond that attained from mere increases in plasma lamotrigine levels. Lamotrigine appears to have negligible to minor effects on the pharmacokinetics of valproic acid.

MANAGEMENT: When coadministered with valproic acid, the dosage of lamotrigine should be half that required in the absence of valproic acid. Patients should be advised to promptly notify their physician if they experience early manifestations of hypersensitivity such as fever, angioedema, and lymphadenopathy, even if a rash is not evident. Lamotrigine should be discontinued if an alternative etiology for these symptoms cannot be established. Likewise, the drug should be discontinued at the first sign of rash, unless the rash is clearly not drug-related.

References

  1. Reutens DC, Duncan JS, Patsalos PN (1993) "Disabling tremor after lamotrigine with sodium valproate." Lancet, 342, p. 185-6
  2. Pisani F, Di Perri R, Perucca E, Richens A (1993) "Interaction of lamotrigine with sodium valproate." Lancet, 341, p. 1224
  3. Binnie CD, van Emde Boas W, Kasteleijn-Nolste-Trenite DG, de Korte RA, Meijer JW, Meinardi H, Miller AA, Overweg J, Peck AW, van Wieringen A (1986) "Acute effects of lamotrigine (BW430C) in persons with epilepsy." Epilepsia, 27, p. 248-54
  4. Magdalou J, Herber R, Bidault R, Siest G (1992) "In vitro N-glucuronidation of a novel antiepileptic drug, lamotrigine, by human liver microsomes." J Pharmacol Exp Ther, 260, p. 1166-73
  5. Brodie MJ (1992) "Lamotrigine." Lancet, 339, p. 1397-400
  6. Panayiotopoulos CP, Ferrie CD, Knott C, Robinson RO (1993) "Interaction of lamotrigine with sodium valproate." Lancet, 341, p. 445
  7. Yuen AW, Land G, Weatherley BC, Peck AW (1992) "Sodium valproate acutely inhibits lamotrigine metabolism." Br J Clin Pharmacol, 33, p. 511-3
  8. Sander JW, Patsalos PN, Oxley JR, Hamilton MJ, Yuen WC (1990) "A randomised double-blind placebo-controlled add-on trial of lamotrigine in patients with severe epilepsy." Epilepsy Res, 6, p. 221-6
  9. Binnie CD, Debets RM, Engelsman M, Meijer JW, Meinardi H, Overweg J, Peck AW, Van Wieringen A, Yuen WC (1989) "Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy." Epilepsy Res, 4, p. 222-9
  10. Jawad S, Yuen WC, Peck AW, Hamilton MJ, Oxley JR, Richens A (1987) "Lamotrigine: single-dose pharmacokinetics and initial 1 week experience in refractory epilepsy." Epilepsy Res, 1, p. 194-201
  11. (2001) "Product Information. Lamictal (lamotrigine)." Glaxo Wellcome
  12. Eriksson AS, Hoppu K, Nergardh A, Boreus L (1996) "Pharmacokinetic interactions between lamotrigine and other antiepileptic drugs in children with intractable epilepsy." Epilepsia, 37, p. 769-73
  13. Anderson GD, Yau MK, Gidal BE, Harris SJ, Levy RH, Lai AA, Wolf KB, Wargin WA, Dren AT (1996) "Bidirectional interaction of valproate and lamotrigine in healthy subjects." Clin Pharmacol Ther, 60, p. 145-56
  14. Wadelius M, Karlsson T, Wadelius C, Rane A (1996) "Lamotrigine and toxic epidermal necrolysis." Lancet, 348, p. 1041
  15. Riva R, Albani F, Contin M, Baruzzi A (1996) "Pharmacokinetic interactions between antiepileptic drugs. Clinical considerations." Clin Pharmacokinet, 31, p. 470-93
  16. Sachs B, Ronnau AC, Ruzicka T, Gleichmann E, Schuppe HC (1996) "Lamotrigine and toxic epidermal necrolysis." Lancet, 348, p. 1597
  17. Vauzelle-Kervroedan F, Rey E, Cieuta C, et al. (1996) "Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as add-on therapy in epileptic children." Br J Clin Pharmacol, 41, p. 325-30
  18. Page RL, ONeil MG, Yarbrough DR, Conradi S (1998) "Fatal toxic epidermal necrolysis related to lamotrigine administration." Pharmacotherapy, 18, p. 392-8
  19. Wong IC, Mawer GE, Sander JW (1999) "Factors influencing the incidence of lamotrigine-related skin rash." Ann Pharmacother, 33, p. 1037-42
  20. Morris RG, Black AB, Lam E, Westley IS (2000) "Clinical study of lamotrigine and valproic acid in patients with epilepsy: Using a drug interaction to advantage?." Ther Drug Monit, 22, p. 656-60
  21. Battino D, Croci D, Granata T, Mamoli D, Messina S, Perucca E (2001) "Single-dose pharmacokinetics of lamotrigine in children: Influence of age and antiepileptic comedication." Ther Drug Monit, 23, p. 217-22
  22. Hachad H, Ragueneau-Majlessi I, Levy RH (2002) "New antiepileptic drugs: review on drug interactions." Ther Drug Monit, 24, p. 91-103
  23. Patsalos PN, Froscher W, Pisani F, van Rijn CM (2002) "The importance of drug interactions in epilepsy therapy." Epilepsia, 43, p. 365-85
  24. Mataringa MI, May TW, Rambeck B (2002) "Does lamotrigine influence valproate concentrations?" Ther Drug Monit, 24, p. 631-6
View all 24 references

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Drug and food interactions

Moderate

lamoTRIgine food

Applies to: Lamictal (lamotrigine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

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Moderate

divalproex sodium food

Applies to: Depakote (divalproex sodium)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

Switch to consumer interaction data

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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