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Drug Interactions between Mellaril-S and Theomax DF

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

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Major

thioridazine hydrOXYzine

Applies to: Mellaril-S (thioridazine) and Theomax DF (ephedrine / hydroxyzine / theophylline)

CONTRAINDICATED: Thioridazine can cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. Thioridazine treatment alone has been associated with several reported cases of torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). In addition, certain agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive parasympatholytic and central nervous system-depressant effects when used in combination with thioridazine. Excessive parasympatholytic effects may include paralytic ileus, hyperthermia, mydriasis, blurred vision, tachycardia, urinary retention, psychosis, and seizures.

MANAGEMENT: Coadministration of thioridazine with other drugs that can prolong the QT interval is considered contraindicated.

References

  1. Fletcher GF, Kazamias TM (1969) "Cardiotoxic effects of Mellaril: conduction disturbances and supraventricular arrhythmias." Am Heart J, 78, p. 135-8
  2. Liberatore MA, Robinson DS (1984) "Torsade de pointes: a mechanism for sudden death associated with neuroleptic drug therapy?" J Clin Psychopharmacol, 4, p. 143-6
  3. (2001) "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation
  4. 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
  5. Glassman AH, Bigger JT Jr (2001) "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry, 158, p. 1774-82
  6. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  7. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  8. Cerner Multum, Inc. "Australian Product Information."
  9. EMA. European Medicines Agency. European Union (2013) EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852
View all 9 references

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Moderate

thioridazine ePHEDrine

Applies to: Mellaril-S (thioridazine) and Theomax DF (ephedrine / hydroxyzine / theophylline)

GENERALLY AVOID: Phenothiazines may antagonize the pharmacologic effects of amphetamine, amphetamine derivatives, and other centrally-acting sympathomimetic agents (i.e., CNS stimulants). Conversely, these agents may diminish the neuroleptic efficacy of phenothiazines. The exact mechanism of interaction is unknown but may involve opposing effects on dopaminergic activity. Several clinical studies have demonstrated the reduction or lack of effect of amphetamines on weight loss in obese psychiatric patients treated with chlorpromazine and other neuroleptic agents. In one of these studies, dextroamphetamine also had no effect on sleep patterns. As for the reverse interaction, it is uncertain whether CNS stimulants actually antagonize the neuroleptic effect of phenothiazines, since CNS stimulants alone have been reported to cause or aggravate preexisting psychotic symptoms. Finally, it is conceivable that, because of their sympathomimetic effects, CNS stimulants may also potentiate the arrhythmogenicity of phenothiazines. A case of fatal ventricular arrhythmia was reported in a patient treated chronically with thioridazine who ingested a single capsule containing phenylpropanolamine 50 mg and chlorpheniramine 4 mg. However, a causal relationship was not established.

MANAGEMENT: Amphetamine, amphetamine derivatives, and other CNS stimulants should generally not be used, particularly for weight reduction, in patients treated with phenothiazines.

References

  1. Reid AA (1964) "Pharmacological antagonism between chlorpromazine and phenmetrazine in mental hospital patients." Med J Aust, 1, p. 187-8
  2. Sletten IW, Ognjanov V, Menendez S, Sundland D, El-Toumi A (1967) "Weight reduction with chlorphentermine and phenmetrazine in obese psychiatric patients during chlorpromazine therapy." Curr Ther Res Clin Exp, 9, p. 570-5
  3. Chouinard G, Ghadirian AM, Jones BD (1978) "Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac*C capsule." Can Med Assoc J, 119, p. 729-31
  4. Casey JF, Hollister LE, Klett CJ, Lasky JJ, Caffey EM (1961) "Combined drug therapy of chronic schizophrenics." Am J Psychiatry, 177, p. 997
  5. Modell W, Hussar AE (1965) "Failure of dextroamphetamine sulfate to incluence eating and sleeping patterns in obese schizophrenic patients." JAMA, 193, p. 275-8
  6. Angrist B, Lee HK, Gershon S (1974) "The antagonism of amphetamine-induced symptomatology by a neuroleptic." Am J Psychiatry, 131, p. 817-9
  7. Cornelius JR, Soloff PH, Reynolds CF, 3d (1984) "Paranoia, homicidal behavior, and seizures associated with phenylpropanolamine." Am J Psychiatry, 141, p. 120-1
  8. Achor MB, Extein I (1981) "Diet aids, mania, and affective illness" Am J Psychiatry, 138, p. 392
  9. Schaffer CB, Pauli MW (1980) "Psychotic reaction caused by proprietary oral diet agents." Am J Psychiatry, 137, p. 1256-7
  10. Grieger TA, Clayton AH, Goyer PF (1990) "Affective disorder following use of phenylpropanolamine" Am J Psychiatry, 147, p. 367-8
  11. Dietz AJ, Jr (1981) "Amphetamine-like reactions to phenylpropanolamine." JAMA, 245, p. 601-2
  12. Norvenius G, Widerlov E, Lonnerholm G (1979) "Phenylpropanolamine and mental disturbances" Lancet, 2, p. 1367-8
  13. Mueller SM (1983) "Neurologic complications of phenylpropanolamine use." Neurology, 33, p. 650-2
  14. Lake CR, Tenglin R, Chernow B, Holloway HC (1983) "Psychomotor stimulant-induced mania in a genetically predisposed patient: a review of the literature and report of a case." J Clin Psychopharmacol, 3, p. 97-100
  15. Lake CR (1991) "Manic psychosis after coffee and phenylpropanolamine." Biol Psychiatry, 30, p. 401-4
  16. Lambert MT (1987) "Paranoid psychoses after abuse of proprietary cold remedies." Br J Psychiatry, 151:, p. 548-50
  17. Wharton BK (1970) "Nasal decongestants and paranoid psychosis." Br J Psychiatry, 117, p. 439-40
  18. Dewsnap P, Libby G (1992) "A case of affective psychosis after routine use of proprietary cold remedy containing phenylpropanolamine" Hum Exp Toxicol, 11, p. 295-6
  19. Finton CK, Barton M, Chernow B (1982) "Possible adverse effects of phenylpropanolamine (diet pills) on sympathetic nervous system function--caveat emptor!" Mil Med, 147, p. 1072
  20. Stroe AE, Hall J, Amin F (1995) "Psychotic episode related to phenylpropanolamine and amantadine in a healthy female." Gen Hosp Psychiatry, 17, p. 457-8
  21. Marshall RD, Douglas CJ (1994) "Phenylpropanolamine-induced psychosis: potential predisposing factors." Gen Hosp Psychiatry, 16, p. 358-60
  22. (2001) "Product Information. Fastin (phentermine)." SmithKline Beecham
  23. (2001) "Product Information. Cylert (pemoline)." Abbott Pharmaceutical
  24. (2001) "Product Information. Ritalin (methylphenidate)." Novartis Pharmaceuticals
  25. (2001) "Product Information. Desoxyn (methamphetamine)." Abbott Pharmaceutical
  26. (2001) "Product Information. Dexedrine (dextroamphetamine)." SmithKline Beecham
  27. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  28. (2001) "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn
  29. (2001) "Product Information. Prelu-2 (phendimetrazine)." Boehringer-Ingelheim
  30. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  31. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  32. Markowitz JS, Patrick KS (2001) "Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder." Clin Pharmacokinet, 40, p. 753-72
  33. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  34. (2007) "Product Information. Vyvanse (lisdexamfetamine)." Shire US Inc
View all 34 references

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Minor

theophylline ePHEDrine

Applies to: Theomax DF (ephedrine / hydroxyzine / theophylline) and Theomax DF (ephedrine / hydroxyzine / theophylline)

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

Moderate

theophylline food

Applies to: Theomax DF (ephedrine / hydroxyzine / theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

ADJUST DOSING INTERVAL: Administration of theophylline with continuous enteral nutrition may reduce the serum levels or the rate of absorption of theophylline. The mechanism has not been reported. In one case, theophylline levels decreased by 53% in a patient receiving continuous nasogastric tube feedings and occurred with both theophylline tablet and liquid formulations, but not with intravenous aminophylline.

MANAGEMENT: When administered to patients receiving continuous enteral nutrition , some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of theophylline is given; rapid-release formulations are preferable, and theophylline levels should be monitored.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
  3. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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Moderate

hydrOXYzine food

Applies to: Theomax DF (ephedrine / hydroxyzine / theophylline)

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

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Moderate

thioridazine food

Applies to: Mellaril-S (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

theophylline food

Applies to: Theomax DF (ephedrine / hydroxyzine / theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8

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Moderate

ePHEDrine food

Applies to: Theomax DF (ephedrine / hydroxyzine / theophylline)

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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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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