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Drug Interactions between bupropion and Mellaril

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

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Interactions between your drugs

Major

buPROPion thioridazine

Applies to: bupropion and Mellaril (thioridazine)

CONTRAINDICATED: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations and adverse effects of thioridazine and its two active metabolites, mesoridazine and sulforidazine, all of which are substrates of the isoenzyme. A study in 19 healthy male patients reviewed thioridazine metabolism in 6 slow and 13 rapid hydroxylators of debrisoquin (the rate of which is believed to be dependent upon the level of CYP450 2D6 activity). A single oral dose of thioridazine (25 mg) produced a 2.4-fold higher peak plasma concentration (Cmax) and a 4.5-fold higher systemic exposure (AUC) for thioridazine in the slow hydroxylators, which is predicted to be similar to what would be seen in patients on CYP450 2D6 inhibitors. Additionally, significant increases (up to severalfold) have been observed during coadministration with fluvoxamine, propranolol, and pindolol in pharmacokinetic studies, although these reductions in clearance may be via other currently unknown mechanisms. The use of thioridazine has been associated with dose-related prolongation of the QT interval, thus elevated plasma levels of the drug may potentiate the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes as well as cardiac arrest and sudden death. Several cases of torsade de pointes have been reported.

MANAGEMENT: The use of thioridazine with fluvoxamine, propranolol, pindolol and/or drugs that inhibit CYP450 2D6 is considered contraindicated. Depending on the elimination half-life of these drugs, a considerable waiting period may be appropriate following their discontinuation before thioridazine is initiated. For example, the manufacturer of fluoxetine recommends that thioridazine not be administered within 5 weeks after discontinuing fluoxetine because of the drug's long half-life. In addition, the prolonged duration of CYP450 2D6 inhibition by the moderate CYP450 2D6 inhibitor rolapitant of at least 28 days after its administration should also be taken into account.

References

  1. Silver JM, Yudofsky SC, Kogan M, Katz BL (1986) "Elevation of thioridazine plasma levels by propranolol." Am J Psychiatry, 143, p. 1290-2
  2. Greendyke RM, Kanter DR (1987) "Plasma propranolol levels and their effect on plasma thioridazine and haloperidol concentrations." J Clin Psychopharmacol, 7, p. 178-82
  3. Greendyke RM, Gulya A (1988) "Effect of pindolol administration on serum levels of thioridazine, haloperidol, phenytoin, and phenobarbital." J Clin Psychiatry, 49, p. 105-7
  4. Abernethy DR, Greenblatt DJ, Steel K, Shader RI (1982) "Impairment of hepatic drug oxidation by propoxyphene." Ann Intern Med, 97, p. 223-4
  5. (2001) "Product Information. Prozac (fluoxetine)." Dista Products Company
  6. Fletcher GF, Kazamias TM (1969) "Cardiotoxic effects of Mellaril: conduction disturbances and supraventricular arrhythmias." Am Heart J, 78, p. 135-8
  7. Markowitz JS, Wells BG, Carson WH (1995) "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother, 29, p. 603-9
  8. (2001) "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation
  9. Thomas M, Maconochie JG, Fletcher E (1996) "The dilemma of the prolonged QT interval in early drug studies." Br J Clin Pharmacol, 41, p. 77-81
  10. Hartigan-Go K, Bateman DN, Nyberg G, Martensson E, Thomas SHL (1996) "Concentration-related pharmacodynamic effects of thioridazine and its metabolites in humans." Clin Pharmacol Ther, 60, p. 543-53
  11. Carrillo JA, Ramos SI, Herraiz AG, Llerena A, Agundez JAG, Berecz R, Duran M, Benitez J (1999) "Pharmacokinetic interaction of fluvoxamine and thioridazine in schizophrenic patients." J Clin Psychopharmacol, 19, p. 494-9
  12. Glassman AH, Bigger JT Jr (2001) "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry, 158, p. 1774-82
  13. (2015) "Product Information. Varubi (rolapitant)." Tesaro Inc.
  14. (2019) "Product Information. Thioridazine Hydrochloride (thioridazine)." Mylan Institutional (formerly UDL Laboratories)
View all 14 references

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Drug and food interactions

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 (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

thioridazine food

Applies to: Mellaril (thioridazine)

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.

References

  1. Lutz EG (1976) "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA, 236, p. 2422-3
  2. Freed E (1981) "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust, 2, p. 44-5

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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. (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

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. (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.

Further information

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