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Drug Interactions between ephedrine / phenobarbital / potassium iodide / theophylline and Haldol

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

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Interactions between your drugs

Major

haloperidol PHENobarbital

Applies to: Haldol (haloperidol) and ephedrine / phenobarbital / potassium iodide / theophylline

MONITOR CLOSELY: Rifampin and other strong CYP450 3A4 inducers may significantly decrease serum concentrations of haloperidol. The mechanism may be related to induction of the CYP450 3A4 metabolism of haloperidol. In an observational study of 12 schizophrenic patients taking oral haloperidol, the administration of rifampin for 28 days reduced haloperidol plasma levels by a mean of 70%, and scores in the Brief Psychiatric Rating Scale (BPRS) were increased. In the same study, another 5 schizophrenic patients receiving haloperidol and rifampin had rifampin discontinued, which led to a mean 3.3-fold increase in haloperidol blood levels. Another observational study involving schizophrenic patients (n=7) also reported significant reduction of serum haloperidol concentration and reduction in haloperidol half-life from 9.4 hours in the control group to 4.9 hours in the rifampin and haloperidol group.

MANAGEMENT: Close observation for reduced clinical effects is recommended if these drugs must be used together. It may be necessary to adjust haloperidol dosage and/or dosage interval whenever a strong CYP450 3A4 inducer is added to or discontinued from therapy.

References

  1. Takeda M, Nishinuma K, Yamashita S, et al. "Serum haloperidol levels of schizophrenics receiving treatment for tuberculosis." Clin Neuropharmacol 9 (1986): 386-97
  2. Borcherding SM, Baciewicz AM, Self TH "Update on rifampin drug interactions." Arch Intern Med 152 (1992): 711-6
  3. "Product Information. Haldol (haloperidol)." McNeil Pharmaceutical PROD (2002):
  4. "Product Information. Rifadin (rifampin)." Hoechst Marion Roussel PROD (2001):
  5. "Product Information. Lysodren (mitotane)." Bristol-Myers Squibb PROD (2001):
  6. Kim YH, Cha IJ, Shim JC, Shin JG, Yoon YR, Kim YK, Kim JI, Park GH, Jang IJ, Woo JI, Shin SG "Effect of rifampin on the plasma concentration and the clinical effect of haloperidol concomitantly administered to schizophrenic patients." J Clin Psychopharmacol 16 (1996): 247-52
  7. Strayhorn VA, Baciewicz AM, Self TH "Update on rifampin drug interactions, III." Arch Intern Med 157 (1997): 2453-8
  8. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  9. Cerner Multum, Inc. "Australian Product Information." O 0
  10. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
  11. "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals (2015):
  12. Cerner Multum, Inc "ANVISA Bulário Eletrônico." O 0 (2015):
  13. Hesslinger B, Normann C, Langosch J, Klose P, Berger M, Walden J "Effects of carbamazepine and valproate on haloperidol plasma levels and on psychopathologic outcome in schizophrenic patients." J Clin Psychopharmacol 19 (1999): 310-5
View all 13 references

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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

haloperidol ePHEDrine

Applies to: Haldol (haloperidol) and ephedrine / phenobarbital / potassium iodide / theophylline

GENERALLY AVOID: Butyrophenone neuroleptics 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 butyrophenones. 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 haloperidol and other neuroleptic agents, most notably chlorpromazine. In one of these studies, dextroamphetamine also had no effect on sleep patterns. Another study found haloperidol to inhibit amphetamine-induced symptoms and may be useful in amphetamine intoxication. As for the reverse interaction, it is uncertain whether CNS stimulants actually antagonize the neuroleptic effect of butyrophenones, since CNS stimulants alone have been reported to cause or aggravate preexisting psychotic symptoms. There has also been a report of acute dystonia occurring in two normal, healthy young women given haloperidol and dexamphetamine as part of a neuropharmacological study. The authors postulated that the reaction was due to a potentiation of dopamine release.

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

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. Casey JF, Hollister LE, Klett CJ, Lasky JJ, Caffey EM "Combined drug therapy of chronic schizophrenics." Am J Psychiatry 177 (1961): 997
  4. Modell W, Hussar AE "Failure of dextroamphetamine sulfate to incluence eating and sleeping patterns in obese schizophrenic patients." JAMA 193 (1965): 275-8
  5. Angrist B, Lee HK, Gershon S "The antagonism of amphetamine-induced symptomatology by a neuroleptic." Am J Psychiatry 131 (1974): 817-9
  6. Cornelius JR, Soloff PH, Reynolds CF, 3d "Paranoia, homicidal behavior, and seizures associated with phenylpropanolamine." Am J Psychiatry 141 (1984): 120-1
  7. Achor MB, Extein I "Diet aids, mania, and affective illness" Am J Psychiatry 138 (1981): 392
  8. Schaffer CB, Pauli MW "Psychotic reaction caused by proprietary oral diet agents." Am J Psychiatry 137 (1980): 1256-7
  9. Grieger TA, Clayton AH, Goyer PF "Affective disorder following use of phenylpropanolamine" Am J Psychiatry 147 (1990): 367-8
  10. Dietz AJ, Jr "Amphetamine-like reactions to phenylpropanolamine." JAMA 245 (1981): 601-2
  11. Norvenius G, Widerlov E, Lonnerholm G "Phenylpropanolamine and mental disturbances" Lancet 2 (1979): 1367-8
  12. Mueller SM "Neurologic complications of phenylpropanolamine use." Neurology 33 (1983): 650-2
  13. 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
  14. Capstick C, Checkley S, Gray J, Dawe S "Dystonia induced by amphetamine and haloperidol." Br J Psychiatry 165 (1994): 276
  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. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  23. "Product Information. Vyvanse (lisdexamfetamine)." Shire US Inc (2007):
View all 23 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

haloperidol food

Applies to: Haldol (haloperidol)

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):
View all 4 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

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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