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7 Interactions found for:

Wellbutrin XL and trazodone
Interactions Summary
  • 5 Major
  • 2 Moderate
  • 0 Minor
  • Wellbutrin XL
  • trazodone

Drug Interactions

Major
Wellbutrin Xl + Trazodone

The following applies to the ingredients: Bupropion (found in Wellbutrin Xl) and Trazodone

ADJUST DOSE: Coadministration of bupropion may elevate the plasma concentrations of drugs metabolized by CYP450 2D6. The proposed mechanism is decreased clearance due to bupropion's inhibition of CYP450 2D6 activity. 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. In addition, when combined with serotonergic drugs, such as certain selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs) that are CYP450 2D6 substrates, elevated plasma levels may potentiate the risk of a potentially life-threatening condition called serotonin syndrome. In a case report of a 62-year-old woman with depression, serotonin syndrome developed after three weeks of bupropion and sertraline therapy, initially misdiagnosed as worsening depression and treated with venlafaxine, leading to further symptom progression. The patient recovered after discontinuing the offending medications and treating for serotonin syndrome, with authors highlighting bupropion's role in increasing SSRI levels through CYP450 2D6 inhibition. Symptoms of serotonin syndrome include altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor.

MONITOR CLOSELY: The use of bupropion is associated with a dose-related risk of seizures. The risk may be further increased when coadministered with serotonergic agents that can reduce the seizure threshold such as certain selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs). These agents are often individually epileptogenic and may have additive effects when combined. The estimated incidence of seizures is approximately 0.4% for immediate-release bupropion hydrochloride at dosages between 300 to 450 mg/day (equivalent to 348 to 522 mg/day of bupropion hydrobromide) but increases almost tenfold between 450 mg and 600 mg/day (equivalent to 522 and 696 mg/day of bupropion hydrobromide). Data for sustained-release (SR) bupropion hydrochloride revealed a seizure incidence of approximately 0.1% at dosages up to 300 mg/day and 0.4% at 400 mg/day. Likewise, in clinical trials, an overall seizure incidence of approximately 0.1% has been reported with extended-release (XL) bupropion hydrochloride at dosages up to 450 mg/day and approximately 0.39% at 450 mg/day. The 0.4% seizure incidence may exceed that of other marketed antidepressants by as much as 4-fold.

MANAGEMENT: According to bupropion product labeling, if coadministration of bupropion with CYP450 2D6 substrates is required, concomitant medications should be initiated at the lower end of the dose range. If the concomitant agents possess serotonergic activity (e.g., SSRIs, SNRIs, and/or TCAs) patients should be monitored more closely for and counseled about the signs and symptoms of serotonin syndrome (e.g., altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor). Additionally, if the coadministered agent is known to lower the seizure threshold, extreme caution is advised particularly in the elderly and in patients with a history of seizures or other risk factors for seizures (e.g., head trauma; brain tumor; severe hepatic cirrhosis; metabolic disorders; CNS infections; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; diabetes treated with oral hypoglycemic agents or insulin). Bupropion as well as concomitant medications should be initiated at the lower end of the dosage range and titrated gradually as needed and as tolerated. The maximum recommended dosage for the specific bupropion formulation should not be exceeded. Bupropion should be discontinued and not restarted in patients who experience a seizure during treatment.

References

  1. "Product Information. Zyban SR (bupropion)." GlaxoSmithKline Australia Pty Ltd (2024):
  2. "Product Information. Zyban (bupropion)." GlaxoSmithKline UK Ltd (2024):
  3. "Product Information. Teva-Bupropion XL (bupropion)." Teva Canada Limited (2021):
  4. "Product Information. BuPROPion Hydrochloride XL (buPROPion)." Camber Pharmaceuticals, Inc (2023):
  5. Munoz RP "Serotonin syndrome induced by a combination of bupropion and SSRIs https://pubmed.ncbi.nlm.nih.gov/15602102/" (2024):

Drug and Food Interactions

Moderate
Wellbutrin Xl + Food

The following applies to the ingredients: Bupropion (found in Wellbutrin Xl)

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):

The following applies to the ingredients: Bupropion (found in Wellbutrin Xl)

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):

The following applies to the ingredients: Bupropion (found in Wellbutrin Xl)

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):

Moderate
Trazodone + Food

The following applies to the ingredients: Trazodone

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):

Drug and Pregnancy Interactions

The following applies to the ingredients: Bupropion (found in Wellbutrin Xl)

This drug should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Smoking cessation without the use of medications is advisable during pregnancy.

AU TGA pregnancy category: B2
US FDA pregnancy category: C

Comments:
-A pregnancy exposure registry is available.
-Neonates exposed to this drug late in the third trimester may require respiratory support, tube feeding, and/or prolonged hospitalization.
-Exposed neonates should be monitored after delivery for direct toxic effects of this drug, drug discontinuation syndrome, and serotonin syndrome (e.g.,. respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo/hypertonia, hyperreflexia, tremor, jitteriness, irritability, constant crying).

High dose animal studies have failed to reveal evidence of specific teratogenic effects. Low dose animal studies in rabbits have reported a slightly increased incidence of fetal malformations and skeletal variations. Epidemiological studies of pregnant women exposed to bupropion in the first trimester show no increased risk of congenital malformations overall.

Data from the international bupropion pregnancy register (675 trimester exposures) and a retrospective cohort study using the United Healthcare database (1,213 first trimester exposures) and a case-control study from the National Birth Defects Prevention Study (6,853 infants with cardiovascular malformations and 5,763 with non-cardiovascular malformations) did not show an increased risk for malformations overall after bupropion exposure during the first trimester. A retrospective database of infants (n=7005) whose mothers were exposed to bupropion in the first trimester and outside of the first trimester also failed to reveal an increased risk for congenital malformation, especially cardiovascular malformation. Study findings on the risk for left ventricular outflow tract obstruction and ventricular septal defect after first trimester exposure to bupropion are inconclusive.

To monitor maternal-fetal outcomes of pregnant women exposed to antidepressant therapy, a National Pregnancy Registry for Antidepressants has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/

AU TGA pregnancy category B2: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.

US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

References

  1. "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome PROD (2001):
  2. "Product Information. Wellbutrin SR (bupropion)." Glaxo Wellcome PROD (2001):
  3. "Product Information. Zyban (bupropion)." Glaxo Wellcome PROD (2001):
  4. "Product Information. Wellbutrin XL (bupropion)." GlaxoSmithKline (2003):
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. "Product Information. Aplenzin (bupropion)." sanofi-aventis (2009):

The following applies to the ingredients: Trazodone

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.
-Some experts recommend: Use with caution; use should be avoided during the first trimester of pregnancy.

US FDA pregnancy category: C

Comment: When this drug is used until delivery, newborns should be monitored for the occurrence of withdrawal symptoms.

Animal studies have revealed evidence of increased fetal resorption and congenital anomalies in adolescents. Other animal models have failed to reveal evidence of adverse effects on embryofetal development, parturition, or postnatal development when given at therapeutic doses. There are no controlled data in human pregnancy.

US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

References

  1. "Product Information. Desyrel (trazodone)." Bristol-Myers Squibb PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

Drug and Breastfeeding Interactions

The following applies to the ingredients: Bupropion (found in Wellbutrin Xl)

A decision should be made to discontinue nursing or discontinue the drug, taking into account the benefit of breast-feeding to the infant and the importance of the drug to the mother.
-Some experts recommend: Use with caution.

Excreted into human milk: Yes

Comment: Another drug may be preferred, particularly when breastfeeding a newborn or preterm infant.

There is limited information that maternal bupropion at oral doses up to 300 mg daily produces low levels in breastmilk. It is not generally expected to cause adverse effects in breastfed infants; however, there are case reports of possible seizure in partially breastfed 6-month-olds. Alternate drugs that may be considered in place of bupropion include nortriptyline, paroxetine, and sertraline.

One case report has suggested that bupropion accumulates in human breast milk in concentrations much greater than in maternal plasma. At least two metabolites of bupropion are also detectable in human milk. However, in the plasma of one nursing infant whose mother took bupropion, neither bupropion nor its metabolites could be detected.

Data from a lactation study in 10 women showed breastmilk levels of 45.2 mcg/L for bupropion, and 104.6 mcg/mL, 72.1 mcg/mL, and 459 mcg/mL for it metabolites hydroxybupropion, erythrohydroxybupropion, and threohydroxybupropion, respectively. The authors of this study estimated that an exclusively breastfed infant would receive an average of 0.2% of the maternal weight-adjusted dose of bupropion and an average of 2% of the maternal weight-adjusted dosage of bupropion plus metabolites.

References

  1. "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome PROD (2001):
  2. "Product Information. Wellbutrin SR (bupropion)." Glaxo Wellcome PROD (2001):
  3. "Product Information. Zyban (bupropion)." Glaxo Wellcome PROD (2001):
  4. "Product Information. Wellbutrin XL (bupropion)." GlaxoSmithKline (2003):
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. "Product Information. Aplenzin (bupropion)." sanofi-aventis (2009):
  8. United States National Library of Medicine "Toxnet. Toxicology Data Network. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT" (2013):

The following applies to the ingredients: Trazodone

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.
-Some experts recommend: Caution is recommended.

Excreted into human milk: Yes

Comments:
-The effects in the nursing infant are unknown.
-The American Academy of Pediatrics considers this agent a drug for which the effect on nursing infants is unknown but may be of concern.

References

  1. "Product Information. Desyrel (trazodone)." Bristol-Myers Squibb PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Briggs GG, Freeman RK. "Drugs in Pregnancy and Lactation." Philadelphia, PA: Wolters Kluwer Health (2015):

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.

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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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