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Potential for other drugs affecting WELLBUTRIN SR: In vitro studies show that bupropion is mainly metabolized to hydroxybupropion CYP2B6. Hence, the potential for drug interactions exists between WELLBUTRIN SR and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies show that paroxetine, sertraline norfluoxetine, fluvoxamine and nelfinavir inhibit the hydroxylation of bupropion.
CYP2B6 inhibitors: ticlopidine, clopidogrel: In a trial on healthy male volunteers, clopidogrel 75 mg once a day or ticlopidine 250 mg twice a day increased the exposure (Cmax and AUC) of bupropion by 40% and 60% for clopidogrel and 38% and 85% for ticlopidine, respectively. the effects (Cmax and AUC) of hydroxybupropion decreased by 50% and 52%, respectively, with clopidogrel and 78% and 84%, respectively, with ticlopidine. This effect is thought to be due to inhibition of the CYP2B6-catalyzed bupropion hydroxylation.
Prasugrel: Prasugrel is a weak inhibitor of CYP2B6. In healthy people, prasugrel increased the values of Cmax and AUC of bupropion by 14% and 18%, respectively, and reduced values of Cmax and AUC of hydroxybupropion, the active metabolite of bupropion, by 32% and 24%, respectively.
Cimetidine: The metabolite of trehydrobupropion bupropion does not appear to be produced by cytochrome P450 enzymes. the effect of concomitant administration of cimetidine on the pharmacokinetics of bupropion and its active metabolites was studied in 24 healthy young male volunteers. After oral administration of bupropion 300 mg with and without cimetidine 800 mg, the pharmacokinetics of bupropion and hydroxybupropion were not affected. However, there were 16% and 32% increases in AUC and Cmax, respectively, from the combined varieties of trehydrobupropion and erythrohydrobupropion.
Citalopram: Citalopram did not affect the pharmacokinetics of bupropion and its three metabolites.
CYP2B6 inducers: ritonavir and lopinavir: In a healthy voluntary trial, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. Exposure to hydroxybupropion metabolite decreased by 23%, trehydrobupropion decreased by 38%, and erythrohydrobupropion decreased by 48%.
In the second healthy volunteer trial, ritonavir at a dose of 600 mg twice a day reduced the AUC and Cmax of bupropion by 66% and 62%, respectively. The effect of the hydroxybupropion metabolite was reduced by 78%, trehydrobupropion decreased by 50%, and erythrohydrobupropion decreased by 68%.
In another healthy volunteer trial, lopinavir 400 mg / ritonavir 100 mg twice daily reduced bupropion AUC and Cmax by 57%. The AUC and Cmax of hydroxybupropion were reduced by 50% and 31%, respectively.
Efavirenz: In a trial on healthy volunteers, efavirenz 600 mg once a day for 2 weeks reduced the AUC and Cmax of bupropion by about 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged, while the Cmax of hydroxybupropion was increased by 50%.
Carbamazepine, phenobarbital, phenytoin: While there are no systematically studied, these drugs can cause the metabolism of bupropion.
Potential for WELLBUTRIN SR to affect other drugs
Animal data indicate that bupropion may be an inducer of drug-metabolizing enzymes in humans. In one trial, after chronic administration of bupropion 100 mg three times a day to 8 healthy male volunteers for 14 days, there were no signs of induction of their own metabolism. However, there may be potential for clinically important changes in the level of co-administered drugs in the blood.
The drugs are metabolized by CYP2D6: In vitro, bupropion and its metabolites (erythrohydrobupropion, trehydrobupropion, hydroxybupropion) are inhibitors of CYP2D6. In a clinical trial of 15 male subjects (aged 19 to 35 years) who were extensive metabolizers of CYP2D6, bupropion 300 mg per day followed by a single dose of 50 mg of desipramine increased Cmax, AUC and t-half of desipramine on average by about 2-, 5- and 2-x, respectively. The effect was present for at least 7 days after the last dose of bupropion. The simultaneous use of bupropion with other metabolizable CYP2D6 drugs has not been formally studied.
Citalopram: Although citalopram is not primarily metabolized by CYP2D6, in one study bupropion increased citalopram Cmax and AUC by 30% and 40%, respectively.
Lamotrigine: Multiple oral doses of bupropion had no statistically significant effects on the pharmacokinetics of a single dose of lamotrigine in 12 healthy volunteers.
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