Posted by Chairman_MAO on January 29, 2004, at 20:52:16
In reply to Wellbutrin+Dayquil/Nyquil?, posted by webpixie on January 28, 2004, at 18:54:46
Wellbutrin (bupropion) is a potent inhibitor of the CYP2D6 liver enzyme. Dextromethorphan (the cough supressant) is metabolized by this enzyme. I'm not qualified to give you a detailed analysis, but I can tell you that dextromethorphan and cyp2d6 inhibitors don't mix. A friend of mine taking 300mg Wellbutrin SR drank a 6oz bottle of Robitussin Maximum Strength cough syrup (I wish he'd consulted me, I would have adamantly warned against it!) to experience the PCP-like effects and ended up tripping for THREE DAYS (the effects usually last 8-12 hours). Now, you are taking a normal dose, but it could be enough to produce untoward effects. The sudafed's weak stimulant effect (which I consider to be only slightly weaker than Wellbutrin's, heh) may produce an odd synergy with Wellbutrin as well--some people are stimulated by Sudafed, where I've heard others tell me it makes them spacey and lethargic. Doxylamine may produce drowsiness in a small number of those who take it.
From the Wellbutrin monograph:
Drugs Metabolized by Cytochrome P450IID6 (CYP2D6): Many drugs, including most antidepressants (SSRIs, many tricyclics), beta-blockers, antiarrhythmics, and antipsychotics are metabolized by the CYP2D6 isoenzyme. Although bupropion is not metabolized by this isoenzyme, bupropion and hydroxybupropion are inhibitors of the CYP2D6 isoenzyme in vitro. In a study of 15 males subjects (ages 19 to 35 years) who were extensive metabolizers of the CYP2D6 isoenzyme, daily doses of bupropion given as 150 mg twice daily followed by a single dose of 50 mg desipramine increased the Cmax, AUC, and T½ of desipramine by an average of approximately two-, five-and twofold, respectively. The effect was present for at least 7 days after the last dose of bupropion. Comcomitant use of bupropion with other drugs metabolized by CYP2D6 has not been formally studied.
Therefore, co-adminstration of bupropion with drugs that are metabolized by CYP2D6 isoenzyme including certain antidepressants (e.g., nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecanide), should be approached with caution and should be initiated at the lower end of the dose range of the concomitant medication. If bupropion is added to the treatment regimen of a patient already receiving a drug metabolized by CYP2D6, the need to decrease the dose of the original medication should be considered, particularly for those concomitant medications with a narrow therapeutic index.
***
And a case report:
Ther Drug Monit. 2002 Jun;24(3):436-7.
Change from the CYP2D6 extensive metabolizer to the poor metabolizer phenotype during treatment With bupropion.***
Guzey C, Norstrom A, Spigset O.Department of Clinical Pharmacology, University Hospital, N-7006 Trondheim, Norway.
Some data indicate that bupropion inhibits the cytochrome P-450 enzyme CYP2D6, but very little published data is available on the extent of this inhibition. The objective of the present study was to quantify this inhibition in a subject treated with bupropion for smoking cessation. Genotypically, the patient was a CYP2D6 homozygous extensive metabolizer (EM). His CYP2D6 phenotype was assessed using the test drug dextromethorphan before, during, and after treatment with bupropion. During treatment with bupropion, he clearly changed from the EM to the poor metabolizer (PM) phenotype. Although the results from a single patient should be interpreted with great caution, the extent of the interaction indicates that bupropion might be a CYP2D6 inhibitor as potent as the most powerful CYP2D6 inhibitors known, such as quinidine and paroxetine.
poster:Chairman_MAO
thread:306612
URL: http://www.dr-bob.org/babble/20040127/msgs/307075.html