Bupropioninteractions

MAOIs: Increased risk of hypertensive reactions can occur when used concomitantly.

Drugs Metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of antidepressants, (e.g., selective serotonin reuptake inhibitors and many tricyclics), antipsychotics (e.g., haloperidol, risperidone and thioridazine), beta-blockers (e.g., metoprolol) and Type 1C antiarrhythmics (e.g., propafenone and flecainide). Consider dose reduction when using with CONTRAVE.

Digoxin: May decrease plasma digoxin levels. Monitor digoxin levels. Concomitant Treatment with CYP2B6 Inhibitors (e.g., ticlopidine or clopidogrel) can increase bupropion exposure. Do not exceed one tablet twice daily when taken with CYP2B6 inhibitors. CYP2B6 Inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) may reduce efficacy by reducing bupropion exposure, avoid concomitant use. Drugs that Lower Seizure Threshold: Dose CONTRAVE with caution. Dopaminergic Drugs (levodopa and amantadine): CNS toxicity can occur when used concomitantly with CONTRAVE.

Drug-Laboratory Test Interactions: CONTRAVE can cause false- positive urine test results for amphetamines.

7.1 Monoamine

Oxidase Inhibitors (MAOI) Concomitant use of MAOIs and bupropion is contraindicated. Bupropion inhibits the re-uptake of dopamine and norepinephrine and can increase the risk for hypertensive reactions when used concomitantly with drugs that also inhibit the re-uptake of dopamine or norepinephrine, including MAOIs. Studies in animals demonstrate that the acute toxicity of bupropion is enhanced by the MAOI phenelzine. At least 14 days should elapse between discontinuation of an MAOI and initiation of treatment with CONTRAVE. Conversely, at least 14 days should be allowed after stopping CONTRAVE before starting an MAOI.

7.2 Opioid Analgesics

Patients taking CONTRAVE may not fully benefit from treatment with opioid-containing medicines, such as cough and cold remedies, antidiarrheal preparations, and opioid analgesics. In patients requiring intermittent opiate treatment, CONTRAVE therapy should be temporarily discontinued, and opiate dose should not be increased above the standard dose. CONTRAVE may be used with caution after chronic opioid use has been stopped for 7 to 10 days in order to prevent precipitation of withdrawal. During CONTRAVE clinical studies, the use of concomitant opioid or opioid-like medications, including analgesics or antitussives, were excluded.

7.3 Potential for CONTRAVE to

Affect Other Drugs Metabolized by CYP2D6 In a clinical study, CONTRAVE (32 mg naltrexone/360 mg bupropion) daily was coadministered with a 50 mg dose of metoprolol (a CYP2D6 substrate). CONTRAVE increased metoprolol AUC and C max by approximately 4- and 2-fold, respectively, relative to metoprolol alone. Similar clinical drug interactions resulting in increased pharmacokinetic exposure of CYP2D6 substrates have also been observed with bupropion as a single agent with desipramine or venlafaxine. Coadministration of CONTRAVE with drugs that are metabolized by CYP2D6 isozyme including certain antidepressants (SSRIs and many tricyclics), antipsychotics (e.g., haloperidol, risperidone and thioridazine), beta-blockers (e.g., metoprolol) and Type 1C antiarrhythmics (e.g., propafenone and flecainide), should be approached with caution and should be initiated at the lower end of the dose range of the concomitant medication. If CONTRAVE 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. Digoxin Coadministration of CONTRAVE with digoxin may decrease plasma digoxin levels. Monitor plasma digoxin levels in patients treated concomitantly with CONTRAVE and digoxin.

7.4 Potential for

Other Drugs to Affect CONTRAVE Bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between CONTRAVE and drugs that are inhibitors or inducers of CYP2B6.

Inhibitors of CYP2B6: Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposure but decrease hydroxybupropion exposure. During concomitant use with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel), the CONTRAVE daily dose should not exceed two tablets (one tablet each morning and evening).

Inducers of CYP2B6: Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure and may reduce efficacy. Avoiding concomitant use with ritonavir, lopinavir, or efavirenz is recommended.

7.5 Drugs That

Lower Seizure Threshold Use extreme caution when coadministering CONTRAVE with other drugs that lower seizure threshold (e.g., antipsychotics, antidepressants, theophylline, or systemic corticosteroids). Use low initial doses and increase the dose gradually. Concomitant use of other bupropion-containing products is contraindicated.

7.6 Dopaminergic

Drugs (Levodopa and Amantadine) Bupropion, levodopa, and amantadine have dopamine agonist effects. CNS toxicity has been reported when bupropion was coadministered with levodopa or amantadine. Adverse reactions have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. It is presumed that the toxicity results from cumulative dopamine agonist effects. Use caution and monitor for such adverse reactions when administering CONTRAVE concomitantly with these drugs.

7.7 Use with

Alcohol In postmarketing experience, there have been rare reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who were drinking alcohol during treatment with bupropion. The consumption of alcohol during treatment with CONTRAVE should be minimized or avoided.

7.8 Drug-Laboratory

Test Interactions False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion. This is due to lack of specificity of some screening tests. False-positive test results may result even following discontinuation of bupropion therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.