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Drug Interaction Report

6 potential interactions and/or warnings found for the following 2 drugs:

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Major

buPROPion escitalopram

Applies to: bupropion, Lexapro (escitalopram)

MONITOR CLOSELY: The use of bupropion is associated with a dose-related risk of seizures. The risk may be further increased when coadministered with other agents that can reduce the seizure threshold, including selective serotonin reuptake inhibitors (SSRIs) such as citalopram and escitalopram. The estimated incidence of seizures is approximately 0.4% for immediate-release bupropion hydrochloride at dosages between 300 to 450 mg/day (equivalent to 348 to 522 mg/day of bupropion hydrobromide), but increases almost tenfold between 450 mg and 600 mg/day (equivalent to 522 and 696 mg/day of bupropion hydrobromide). Data for sustained-release (SR) bupropion hydrochloride revealed a seizure incidence of approximately 0.1% at dosages up to 300 mg/day and 0.4% at 400 mg/day. Likewise, in clinical trials, an overall seizure incidence of approximately 0.1% has been reported with extended-release (XL) bupropion hydrochloride at dosages up to 450 mg/day and approximately 0.39% at 450 mg/day. The 0.4% seizure incidence may exceed that of other marketed antidepressants by as much as 4-fold.

Pharmacokinetically, bupropion may increase the plasma concentrations of citalopram. The mechanism of interaction has not been described. Unlike other SSRIs, citalopram is not known to be significantly metabolized by CYP450 2D6, which is inhibited by bupropion and its metabolite, hydroxybupropion. In one study, bupropion increased citalopram peak plasma concentration (Cmax) and systemic exposure (AUC) by 30% and 40%, respectively. Citalopram did not affect the pharmacokinetics of bupropion and its three active metabolites. The interaction has not been studied with escitalopram.

MANAGEMENT: Extreme caution is advised if bupropion is administered with any substance that can reduce the seizure threshold, particularly in the elderly and in patients with a history of seizures or other risk factors for seizures (e.g., head trauma; brain tumor; severe hepatic cirrhosis; metabolic disorders; CNS infections; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; diabetes treated with oral hypoglycemic agents or insulin). Bupropion as well as concomitant medications should be initiated at the lower end of the dosage range and titrated gradually as needed and as tolerated. The maximum recommended dosage for the specific bupropion formulation should not be exceeded. Clinical and laboratory monitoring may be appropriate for citalopram or escitalopram whenever bupropion is added to or withdrawn from therapy. Bupropion should be discontinued and not restarted in patients who experience a seizure during treatment.

References

  1. Rosenstein DL, Nelson JC, Jacobs SC (1993) "Seizures associated with antidepressants: a review." J Clin Psychiatry, 54, p. 289-99
  2. James WA, Lippmann S (1991) "Bupropion: overview and prescribing guidelines in depression." South Med J, 84, p. 222-4
  3. Johnston JA, Lineberry CG, Ascher JA, et al. (1991) "A 102-center prospective study of seizure in association with bupropion." J Clin Psychiatry, 52, p. 450-6
  4. Gittelman DK, Kirby MG (1993) "A seizure following bupropion overdose." J Clin Psychiatry, 54, p. 162
  5. Sheehan DV, Welch JB, Fishman SM (1986) "A case of bupropion-induced seizure." J Nerv Ment Dis, 174, p. 496-8
  6. Dufresne RL, Weber SS, Becker RE (1984) "Bupropion hydrochloride." Drug Intell Clin Pharm, 18, p. 957-64
  7. (2001) "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome
  8. Storrow AB (1994) "Bupropion overdose and seizure." Am J Emerg Med, 12, p. 183-4
  9. (2001) "Product Information. Wellbutrin SR (bupropion)." Glaxo Wellcome
  10. (2001) "Product Information. Zyban (bupropion)." Glaxo Wellcome
  11. Guzey C, Norstrom A, Spigset O (2002) "Change from the CYP2D6 extensive metabolizer to the poor metabolizer phenotype during treatment with bupropion." Ther Drug Monit, 24, p. 436-7
  12. Pisani F, Spina E, Oteri G (1999) "Antidepressant drugs and seizure susceptibility: from in vitro data to clinical practice." Epilepsia, 40(Suppl 10), S48-56
  13. (2003) "Product Information. Wellbutrin XL (bupropion)." GlaxoSmithKline
  14. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  15. (2009) "Product Information. Aplenzin (bupropion)." sanofi-aventis
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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.

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