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Drug Interaction Report

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

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Interactions between your drugs

Moderate

metoprolol buPROPion

Applies to: Metoprolol Succinate ER (metoprolol), Wellbutrin XL (bupropion)

ADJUST DOSE: Coadministration with bupropion may increase the plasma concentrations of drugs that are metabolized by CYP450 2D6 (e.g., selective serotonin reuptake inhibitors; tricyclic antidepressants; some beta blockers, antiarrhythmics, and antipsychotics). The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by bupropion. Approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent are extensive metabolizers of CYP450 2D6 and may be affected by this interaction. In a study of 15 male volunteers who were extensive metabolizers of CYP450 2D6, administration of a single 50 mg dose of desipramine following treatment with bupropion 150 mg twice daily increased the desipramine peak plasma concentration (Cmax), systemic exposure (AUC) and half-life by an average of 2-, 5-, and 2-fold, respectively. The effect was present for at least 7 days after the last dose of bupropion. A case report describes a 4-fold increase in plasma levels of imipramine and its metabolite, desipramine, in a 64-year-old woman following the addition of bupropion 225 mg/day. Plasma levels of desipramine were increased twofold more than the imipramine levels, which is consistent with the fact that desipramine is primarily metabolized by CYP450 2D6 while imipramine is also metabolized by other CYP450 isoenzymes. In another report, an 83-year-old woman became unsteady, confused, and lethargic following the addition of bupropion SR 300 mg/day. Her nortriptyline level was found to have increased by 185%. A later rechallenge prompted recurrence of the interaction. Likewise, a 62-year-old woman with no history of seizures developed a generalized tonic-clonic seizure in association with toxic trimipramine plasma levels following the addition of bupropion 300 mg/day. No further seizures occurred following dosage reductions of both drugs.

MANAGEMENT: Caution is advised if bupropion must be used concomitantly with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Concomitant medications should be initiated at the lower end of the dose range. Clinical and laboratory monitoring may be appropriate for some drugs whenever bupropion is added to or withdrawn from therapy.

References

  1. James WA, Lippmann S. Bupropion: overview and prescribing guidelines in depression. South Med J. 1991;84:222-4.
  2. Dufresne RL, Weber SS, Becker RE. Bupropion hydrochloride. Drug Intell Clin Pharm. 1984;18:957-64.
  3. Product Information. Wellbutrin (bupropion). Glaxo Wellcome. 2001;PROD.
  4. Product Information. Wellbutrin SR (bupropion). Glaxo Wellcome. 2001;PROD.
  5. Product Information. Zyban (bupropion). Glaxo Wellcome. 2001;PROD.
  6. Shad MU. A possible bupropion and imipramine interaction. J Clin Psychopharmacol. 1997;17:118.
  7. Guzey C, Norstrom A, Spigset O. Change from the CYP2D6 extensive metabolizer to the poor metabolizer phenotype during treatment with bupropion. Ther Drug Monit. 2002;24:436-7.
  8. Enns MW. Seizure during combination of trimipramine and bupropion. J Clin Psychiatry. 2001;62:476-7.
  9. Product Information. Wellbutrin XL (bupropion). GlaxoSmithKline. 2003.
  10. Shin YW, Erm TM, Choi EJ, Kim SY. A Case of Prolonged Seizure Activity After Combined Use of Bupropion and Clomipramine. Clin Neuropharmacol. 2004;27:192-194.
  11. Product Information. Aplenzin (bupropion). sanofi-aventis. 2009.
View all 11 references

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Drug and food interactions

Moderate

metoprolol food

Applies to: Metoprolol Succinate ER (metoprolol)

ADJUST DOSING INTERVAL: The bioavailability of metoprolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take metoprolol at the same time each day, preferably with or immediately following meals.

References

  1. Product Information. Lopressor (metoprolol). Novartis Pharmaceuticals. 2001;PROD.
  2. Darcy PF. Nutrient-drug interactions. Adverse Drug React Toxicol Rev. 1995;14:233-54.

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Moderate

buPROPion food

Applies to: Wellbutrin XL (bupropion)

GENERALLY AVOID: Excessive use or abrupt discontinuation of alcohol after chronic ingestion may precipitate seizures in patients receiving bupropion. Additionally, there have been rare postmarketing reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who drank alcohol during treatment with bupropion. According to one forensic report, a patient died after taking large doses of both bupropion and alcohol. It is uncertain whether a drug interaction was involved. Single-dose studies in healthy volunteers given bupropion and alcohol failed to demonstrate either a significant pharmacokinetic or pharmacodynamic interaction.

MANAGEMENT: The manufacturer recommends that alcohol consumption be minimized or avoided during bupropion treatment. The use of bupropion is contraindicated in patients undergoing abrupt discontinuation of alcohol.

References

  1. Posner J, Bye A, Jeal S, Peck AW, Whiteman P. Alcohol and bupropion pharmacokinetics in healthy male volunteers. Eur J Clin Pharmacol. 1984;26:627-30.
  2. Ramcharitar V, Levine BS, Goldberger BA, Caplan YH. Bupropion and alcohol fatal intoxication: case report. Forensic Sci Int. 1992;56:151-6.
  3. Hamilton MJ, Bush MS, Peck AW. The effect of bupropion, a new antidepressant drug, and alcohol and their interaction in man. Eur J Clin Pharmacol. 1984;27:75-80.
  4. Product Information. Wellbutrin (bupropion). Glaxo Wellcome. 2001;PROD.
View all 4 references

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Moderate

metoprolol food

Applies to: Metoprolol Succinate ER (metoprolol)

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

References

  1. Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E. Interaction of atenolol with furosemide and calcium and aluminum salts. Clin Pharmacol Ther. 1981;30:429-35.

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Moderate

buPROPion food

Applies to: Wellbutrin XL (bupropion)

MONITOR: Additive or synergistic effects on blood pressure may occur when bupropion is combined with sympathomimetic agents such as nasal decongestants, adrenergic bronchodilators, ophthalmic vasoconstrictors, and systemic vasopressors. Treatment with bupropion can result in elevated blood pressure and hypertension. In clinical practice, hypertension, in some cases severe and requiring acute treatment, has been observed in patients receiving bupropion alone and in combination with nicotine replacement therapy. These events have occurred in both patients with and without evidence of preexisting hypertension. Furthermore, postmarketing cases of hypertensive crisis have been reported during the initial titration phase with bupropion-naltrexone treatment.

MANAGEMENT: Caution is advised when bupropion is used with other drugs that increase dopaminergic or noradrenergic activity due to an increased risk of hypertension. Blood pressure and heart rate should be measured prior to initiating bupropion therapy and monitored at regular intervals consistent with usual clinical practice, particularly in patients with preexisting hypertension. Dose reduction or discontinuation of bupropion should be considered in patients who experience clinically significant and sustained increases in blood pressure or heart rate.

References

  1. Product Information. Auvelity (bupropion-dextromethorphan). Axsome Therapeutics, Inc. 2022;1.
  2. Product Information. Zyban (bupropion). GlaxoSmithKline UK Ltd. 2022.
  3. Product Information. Wellbutrin XL (bupropion). Bausch Health, Canada Inc. 2022.
  4. Product Information. Contrave (bupropion-naltrexone). Currax Pharmaceuticals LLC. 2021.
View all 4 references

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Moderate

buPROPion food

Applies to: Wellbutrin XL (bupropion)

MONITOR: The concomitant use of bupropion and nicotine replacement for smoking cessation may increase the risk of hypertension. In a clinical study (n=250), 6.1% of patients who used sustained-release bupropion with nicotine transdermal system developed treatment-emergent hypertension, compared to 2.5% of patients treated with bupropion alone, 1.6% treated with nicotine alone, and 3.1% treated with placebo. Three patients in the bupropion plus nicotine group and one patient in the nicotine-only group discontinued treatment due to hypertension. The majority had evidence of preexisting hypertension.

MANAGEMENT: Blood pressure monitoring is recommended for patients concomitantly using bupropion and nicotine replacement for smoking cessation.

References

  1. Product Information. Zyban (bupropion). Glaxo Wellcome. 2001;PROD.

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Therapeutic duplication warnings

No duplication 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.


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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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Further information

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