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Drug Interactions between Anergan 50 and ephedrine / phenobarbital / potassium iodide / theophylline

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

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Interactions between your drugs

Moderate

theophylline PHENobarbital

Applies to: ephedrine / phenobarbital / potassium iodide / theophylline and ephedrine / phenobarbital / potassium iodide / theophylline

MONITOR: Barbiturates may decrease serum levels and therapeutic effects of the methylxanthines. The mechanism is barbiturate induction of CYP450 3A4 and 1A2 hepatic metabolism of methylxanthines.

MANAGEMENT: Close observation for clinical and laboratory evidence of decreased methylxanthine effect is indicated if these drugs must be used together. Patients should be advised to notify their physician if they experience a worsening of their respiratory symptoms.

References

  1. Upton RA "Pharmacokinetic interactions between theophylline and other medication (Part I)." Clin Pharmacokinet 20 (1991): 66-80
  2. Bukowskyj M, Nakatsu K, Munt PW "Theophylline reassessed." Ann Intern Med 101 (1984): 63-73
  3. Landay RA, Gonzalez MA, Taylor JC "Effect of phenobarbital on theophylline disposition." J Allergy Clin Immunol 62 (1978): 27-9
  4. Dahlqvist R, Steiner E, Koike Y, von Bahr C, Lind M, Billing B "Induction of theophylline metabolism by pentobarbital." Ther Drug Monit 11 (1989): 408-10
View all 4 references

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Moderate

PHENobarbital promethazine

Applies to: ephedrine / phenobarbital / potassium iodide / theophylline and Anergan 50 (promethazine)

MONITOR: Concomitant use of phenothiazines with barbiturates may reduce the plasma concentrations and therapeutic effects of both agents. The mechanism is unclear but may relate to metabolic induction of CYP450 hepatic enzymes. In addition, coadministration of phenothiazines and barbiturates may lead to a reduction in seizure threshold and additive central nervous system (CNS) and respiratory depressant effects.

MANAGEMENT: Administration of phenothiazines in patients receiving large doses of barbiturates is considered contraindicated by some authorities (US). If coadministration is required, caution as well as clinical and laboratory monitoring should be considered whenever either of these agents is added to or withdrawn from therapy. If chlorpromazine is coadministered with a barbiturate, the manufacturer of chlorpromazine recommends using 1/4 to 1/2 of the usual barbiturate dosage. Patients should be monitored for hypotension, loss of seizure control and the development of adverse effects including CNS and respiratory depression.

References

  1. Harashima H, Sugiyama Y, Sawada Y, Shigenobu K, Kasuya Y, Iga T, Hanano M "Kinetic analysis of the positive inotropic action (PIA) of ouabain in isolated perfused rabbit heart. Slow onset of PIA and slow binding to Na+, K+-adenosine triphosphatase." J Pharmacobiodyn 11 (1988): 533-40
  2. Dundee JW, Moore J "The effects of premedication with phenothiazine derivatives on the course of methohexitone anaesthesia." Br J Anaesth 33 (1961): 382-96
  3. Forrest FM, Forrest IS, Serra MT "Modification of chlorpromazine metabolism by some other drugs frequently administered to psychiatric patients." Biol Psychiatry 2 (1970): 53-8
  4. Linnoila M, Viukari M, Vaisanen K, Auvinen J "Effect of anticonvulsants on plasma haloperidol and thioridazine levels." Am J Psychiatry 137 (1980): 819-21
  5. Ellenor GL, Musa MN, Beuthin FC "Phenobarbital-thioridazine interaction in man." Res Commun Chem Pathol Pharmacol 21 (1978): 185-8
  6. Gay PE, Madsen JA "Interaction between phenobarbital and thioridazine." Neurology 33 (1983): 1631-2
  7. Ellenor GL, Musa MN, Beuthin FC "Phenobarbital--thioridazine interaction in man." Res Commun Chem Pathol Pharmacol 21 (1978): 185-8
  8. "Product Information. FluPHENAZine Decanoate (fluPHENAZine)." Mylan Institutional LLC (2022):
  9. "Product Information. Perphenazine (perphenazine)." Actavis Pharma, Inc. (2019):
  10. "Product Information. Trifluoperazine Hydrochloride (trifluoperazine)." Mylan Institutional (formerly UDL Laboratories) (2019):
  11. "Product Information. Thioridazine Hydrochloride (thioridazine)." Mylan Institutional (formerly UDL Laboratories) (2019):
View all 11 references

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Moderate

ePHEDrine promethazine

Applies to: ephedrine / phenobarbital / potassium iodide / theophylline and Anergan 50 (promethazine)

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

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Minor

theophylline ePHEDrine

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

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Drug and food interactions

Major

PHENobarbital food

Applies to: ephedrine / phenobarbital / potassium iodide / theophylline

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

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Moderate

theophylline food

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

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Moderate

promethazine food

Applies to: Anergan 50 (promethazine)

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

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Moderate

theophylline food

Applies to: ephedrine / phenobarbital / potassium iodide / 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 "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8

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Moderate

ePHEDrine food

Applies to: ephedrine / phenobarbital / potassium iodide / 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 "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
  3. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  4. "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
  5. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  6. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  7. "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
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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