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Drug Interactions between Buproban and dyphylline / ephedrine / guaifenesin / phenobarbital

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

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Interactions between your drugs

Major

buPROPion ePHEDrine

Applies to: Buproban (bupropion) and dyphylline / ephedrine / guaifenesin / phenobarbital

MONITOR CLOSELY: The use of bupropion is associated with a dose-related risk of seizures. The risk may be further increased when coadministered with selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), systemic steroids, or any substance that can reduce the seizure threshold (e.g., carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, lindane, theophylline). 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: Extreme caution is advised if bupropion is administered with any substance that can reduce the seizure threshold, 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. Rosenstein DL, Nelson JC, Jacobs SC (1993) "Seizures associated with antidepressants: a review." J Clin Psychiatry, 54, p. 289-99
  2. James WA, Lippmann S (1991) "Bupropion: overview and prescribing guidelines in depression." South Med J, 84, p. 222-4
  3. Johnston JA, Lineberry CG, Ascher JA, et al. (1991) "A 102-center prospective study of seizure in association with bupropion." J Clin Psychiatry, 52, p. 450-6
  4. Gittelman DK, Kirby MG (1993) "A seizure following bupropion overdose." J Clin Psychiatry, 54, p. 162
  5. Sheehan DV, Welch JB, Fishman SM (1986) "A case of bupropion-induced seizure." J Nerv Ment Dis, 174, p. 496-8
  6. Dufresne RL, Weber SS, Becker RE (1984) "Bupropion hydrochloride." Drug Intell Clin Pharm, 18, p. 957-64
  7. (2001) "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome
  8. Masco HL, Kiev A, Holloman LC, Batey SR, Johnston JA, Lineberry CG (1994) "Safety and efficacy of bupropion and nortriptyline in outpatients with depression." Curr Ther Res Clin Exp, 55, p. 851-63
  9. Storrow AB (1994) "Bupropion overdose and seizure." Am J Emerg Med, 12, p. 183-4
  10. (2001) "Product Information. Wellbutrin SR (bupropion)." Glaxo Wellcome
  11. (2001) "Product Information. Zyban (bupropion)." Glaxo Wellcome
  12. Pisani F, Spina E, Oteri G (1999) "Antidepressant drugs and seizure susceptibility: from in vitro data to clinical practice." Epilepsia, 40(Suppl 10), S48-56
  13. (2003) "Product Information. Wellbutrin XL (bupropion)." GlaxoSmithKline
  14. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  15. (2009) "Product Information. Aplenzin (bupropion)." sanofi-aventis
View all 15 references

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Moderate

buPROPion PHENobarbital

Applies to: Buproban (bupropion) and dyphylline / ephedrine / guaifenesin / phenobarbital

MONITOR: Excessive use or abrupt discontinuation of barbiturates and other sedatives after chronic ingestion may precipitate seizures in patients receiving bupropion. Theoretically, barbiturates may also decrease the plasma concentrations and pharmacologic effects of bupropion due to induction of hepatic CYP450 isoenzymes.

MANAGEMENT: Pharmacologic response to bupropion should be monitored more closely whenever a barbiturate is added to or withdrawn from therapy, and the bupropion dosage adjusted as necessary. Although barbiturates and other sedatives may be prescribed to treat agitation, anxiety, and insomnia associated with bupropion use, patients should be alerted to the possibility of an increased risk of seizures during excessive exposure to these drugs. Patients should not attempt to alter the dosages or discontinue the medications on their own without consulting with their physician. The use of bupropion is contraindicated in patients undergoing abrupt discontinuation of sedatives.

References

  1. James WA, Lippmann S (1991) "Bupropion: overview and prescribing guidelines in depression." South Med J, 84, p. 222-4
  2. (2001) "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome

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Minor

ePHEDrine dyphylline

Applies to: dyphylline / ephedrine / guaifenesin / phenobarbital and dyphylline / ephedrine / guaifenesin / phenobarbital

Ephedrine-methylxanthine combinations are used for the treatment of asthma but the efficacy of the combination has been questioned. This combination may lead to increased xanthine side effects. The mechanism is unknown, but may be related to synergistic pharmacologic effects. Patients using this combination should be closely monitored for side effects such as nausea, vomiting, tachycardia, nervousness, or insomnia. If side effects are noted, the dosage of the xanthine may need to be decreased.

References

  1. Weinberger M, Bronsky E, Bensch GW, Bock GN, Yecies JJ (1975) "Interaction of ephedrine and theophylline." Clin Pharmacol Ther, 17, p. 585-92
  2. Sims JA, doPico GA, Reed CE (1978) "Bronchodilating effect of oral theophylline-ephedrine combination." J Allergy Clin Immunol, 62, p. 15-21
  3. Tinkelman DG, Avner SE (1977) "Ephedrine therapy in asthmatic children. Clinical tolerance and absence of side effects." JAMA, 237, p. 553-7
  4. Weinberger MM, Brousky EA (1974) "Evaluation of oral bronchodilator therapy in asthmatic children: bronchodilators in asthmatic children." J Pediatr, 84, p. 421-7
  5. Badiei B, Faciane J, Sly M (1975) "Effect of throphylline, ephedrine and theri combination upon exercise-induced airway obstruction." Ann Allergy, 35, p. 32-6
View all 5 references

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Drug and food interactions

Major

PHENobarbital food

Applies to: dyphylline / ephedrine / guaifenesin / phenobarbital

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
  3. Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
  4. Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
  5. Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
View all 5 references

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Moderate

buPROPion food

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

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Moderate

buPROPion food

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

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Moderate

ePHEDrine food

Applies to: dyphylline / ephedrine / guaifenesin / phenobarbital

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
View all 7 references

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Moderate

buPROPion food

Applies to: Buproban (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. (2001) "Product Information. Zyban (bupropion)." Glaxo Wellcome

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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.

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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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