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Drug Interactions between bupropion and Di-Phen

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

phenytoin buPROPion

Applies to: Di-Phen (phenytoin) and bupropion

MONITOR: Coadministration with inducers of CYP450 2B6 may decrease the plasma concentrations of bupropion. In vitro findings suggest that CYP450 2B6 is the principal isoenzyme involved in the formation of hydroxybupropion, one of three active metabolites of bupropion. In 12 study patients with mood disorders, administration of a single 150 mg dose of bupropion during treatment with the potent CYP450 2B6 inducer carbamazepine (mean dose 942 mg/day for at least 3 weeks) decreased mean bupropion peak plasma concentration (Cmax) and systemic exposure (AUC) by 87% and 90%, respectively, compared to administration with placebo. Mean Cmax and AUC of two active metabolites were also significantly reduced (86% and 96%, respectively, for erythrohydrobupropion; 81% and 86%, respectively, for threohydrobupropion), while Cmax and AUC of hydroxybupropion increased by 71% and 50%, respectively. In another 13 study subjects administered a 150 mg dose of sustained-release bupropion during treatment with the moderate CYP450 2B6 inducer efavirenz (600 mg once daily for 14 days), bupropion Cmax and AUC decreased by an average of 34% and 55%, respectively, while the Cmax of hydroxybupropion increased by 50% with no change in AUC. Although reduced therapeutic effects of bupropion may be anticipated from these interactions, the full clinical impact is uncertain, since metabolites are present in substantially higher plasma levels than the parent drug but have reduced potencies and possibly varied pharmacologic effects. The potency and toxicity of the metabolites relative to bupropion have not been fully characterized in humans. In an antidepressant screening test performed on mice, hydroxybupropion was found to be one-half as potent as bupropion and both erythrohydrobupropion and threohydrobupropion were 5-fold less potent than bupropion. Another CYP450 2B6 inducer, ritonavir, has also been studied but resulted in decreased plasma concentrations of bupropion and all three metabolites. When coadministered with ritonavir 100 mg twice daily for 17 days, bupropion Cmax and AUC decreased by 21% and 22%, respectively; erythrohydrobupropion Cmax and AUC decreased by 28% and 48%, respectively, threohydrobupropion Cmax and AUC decreased by 39% and 38%, respectively; and hydroxybupropion AUC decreased by 23% with no change in Cmax. When coadministered with ritonavir 600 mg twice daily for 8 days, bupropion Cmax and AUC decreased by 62% and 66%, respectively; erythrohydrobupropion Cmax and AUC decreased by 48% and 68%, respectively, threohydrobupropion Cmax and AUC decreased by 58% and 50%, respectively; and hydroxybupropion Cmax and AUC decreased by 42% and 78%, respectively. When coadministered with lopinavir-ritonavir 400 mg-100 mg twice daily for 14 days, bupropion Cmax and AUC decreased by 57% each, while hydroxybupropion Cmax and AUC decreased by 31% and 50%, respectively.

MANAGEMENT: Pharmacologic response to bupropion should be monitored more closely whenever a CYP450 2B6 inducer is added to or withdrawn from therapy, and the bupropion dosage adjusted as necessary. Concomitant use of potent and moderate CYP450 2B6 inducers such as carbamazepine, efavirenz, rifampin, ritonavir, and lopinavir-ritonavir should be avoided with fixed-dose combination products such as bupropion-naltrexone or bupropion-dextromethorphan. For other bupropion products, increases in bupropion dosage should be guided by clinical response; however, the maximum recommended dosage should not be exceeded.

References

  1. James WA, Lippmann S "Bupropion: overview and prescribing guidelines in depression." South Med J 84 (1991): 222-4
  2. "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome PROD (2001):
  3. Ketter TA, Jenkins JB, Schroeder DH, Pazzaglia PJ, Marangell LB, George MS, Callahan AM, Hinton ML, Chao J, Post RM "Carbamazepine but not valproate induces bupropion metabolism." J Clin Psychopharmacol 15 (1995): 327-33
  4. "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals PROD (2001):
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. "Product Information. Forfivo XL (buPROPion)." Almatica Pharma Inc (2022):
  8. "Product Information. Auvelity (bupropion-dextromethorphan)." Axsome Therapeutics, Inc. 1 (2022):
  9. "Product Information. Zyban (bupropion)." GlaxoSmithKline UK Ltd (2022):
  10. "Product Information. Wellbutrin XL (bupropion)." Bausch Health, Canada Inc. (2022):
  11. "Product Information. Contrave (bupropion-naltrexone)." Currax Pharmaceuticals LLC (2021):
View all 11 references

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Drug and food interactions

Moderate

phenytoin food

Applies to: Di-Phen (phenytoin)

ADJUST DOSING INTERVAL: Phenytoin bioavailability may decrease to subtherapeutic levels when the suspension is given concomitantly with enteral feedings. The mechanism may be related to phenytoin binding to substances in the enteral formula (e.g., calcium, protein) and/or binding to the tube lumen. Data have been conflicting and some studies have reported no changes in phenytoin levels, while others have reported significant reductions.

MONITOR: Acute consumption of alcohol may increase plasma phenytoin levels. Chronic consumption of alcohol may decrease plasma phenytoin levels. The mechanism of this interaction is related to induction of phenytoin metabolism by ethanol during chronic administration. Other hydantoin derivatives may be similarly affected by ethanol.

MANAGEMENT: Some experts have recommended interrupting the feeding for 2 hours before and after the phenytoin dose, giving the phenytoin suspension diluted in water, and flushing the tube with water after administration; however, this method may not entirely avoid the interaction and is not always clinically feasible. Patients should be closely monitored for clinical and laboratory evidence of altered phenytoin efficacy and levels upon initiation and discontinuation of enteral feedings. Dosage adjustments or intravenous administration may be required until therapeutic serum levels are obtained. In addition, patients receiving phenytoin therapy should be warned about the interaction between phenytoin and ethanol and they should be advised to notify their physician if they experience worsening of seizure control or symptoms of toxicity, including drowsiness, visual disturbances, change in mental status, nausea, or ataxia.

References

  1. Sandor P, Sellers EM, Dumbrell M, Khouw V "Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics." Clin Pharmacol Ther 30 (1981): 390-7
  2. Holtz L, Milton J, Sturek JK "Compatibility of medications with enteral feedings." JPEN J Parenter Enteral Nutr 11 (1987): 183-6
  3. Sellers EM, Holloway MR "Drug kinetics and alcohol ingestion." Clin Pharmacokinet 3 (1978): 440-52
  4. "Product Information. Dilantin (phenytoin)." Parke-Davis PROD (2001):
  5. Doak KK, Haas CE, Dunnigan KJ, et al. "Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings." Pharmacotherapy 18 (1998): 637-45
  6. Rodman DP, Stevenson TL, Ray TR "Phenytoin malabsorption after jejunostomy tube delivery." Pharmacotherapy 15 (1995): 801-5
  7. Au Yeung SC, Ensom MH "Phenytoin and enteral feedings: does evidence support an interaction?" Ann Pharmacother 34 (2000): 896-905
  8. Ozuna J, Friel P "Effect of enteral tube feeding on serum phenytoin levels." J Neurosurg Nurs 16 (1984): 289-91
  9. Faraji B, Yu PP "Serum phenytoin levels of patients on gastrostomy tube feeding." J Neurosci Nurs 30 (1998): 55-9
  10. Marvel ME, Bertino JS "Comparative effects of an elemental and a complex enteral feeding formulation on the absorption of phenytoin suspension." JPEN J Parenter Enteral Nutr 15 (1991): 316-8
  11. Fleisher D, Sheth N, Kou JH "Phenytoin interaction with enteral feedings administered through nasogastric tubes." JPEN J Parenter Enteral Nutr 14 (1990): 513-6
  12. Haley CJ, Nelson J "Phenytoin-enteral feeding interaction." DICP 23 (1989): 796-8
  13. Guidry JR, Eastwood TF, Curry SC "Phenytoin absorption in volunteers receiving selected enteral feedings." West J Med 150 (1989): 659-61
  14. Krueger KA, Garnett WR, Comstock TJ, Fitzsimmons WE, Karnes HT, Pellock JM "Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability." Epilepsia 28 (1987): 706-12
  15. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  16. Cerner Multum, Inc. "Australian Product Information." O 0
View all 16 references

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Moderate

buPROPion food

Applies to: 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 26 (1984): 627-30
  2. Ramcharitar V, Levine BS, Goldberger BA, Caplan YH "Bupropion and alcohol fatal intoxication: case report." Forensic Sci Int 56 (1992): 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 27 (1984): 75-80
  4. "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome PROD (2001):
View all 4 references

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Moderate

buPROPion food

Applies to: 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. 1 (2022):
  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: 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 PROD (2001):

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Therapeutic duplication warnings

No 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.

See also

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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.

Further information

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

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