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Drug Interactions between aminophylline / ephedrine / guaifenesin / phenobarbital and hydrocortisone

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

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Interactions between your drugs

Moderate

hydrocortisone PHENobarbital

Applies to: hydrocortisone and aminophylline / ephedrine / guaifenesin / phenobarbital

MONITOR: Barbiturates may decrease the plasma concentrations and systemic effects of both endogenous and exogenous corticosteroids. The mechanism is accelerated corticosteroid metabolism due to induction of the CYP450 3A4 enzymatic pathway by barbiturates.

MANAGEMENT: Patients treated concomitantly with a barbiturate may require higher dosages of corticosteroids or adrenocorticotropic agents. Pharmacologic response to these agents should be monitored more closely whenever a barbiturate is added to or withdrawn from therapy in patients stabilized on their existing corticosteroid or adrenocorticotropic regimen, and the dosage(s) adjusted as necessary.

References (10)
  1. Bartoszek M, Brenner AM, Szefler SJ (1987) "Prednisolone and methylprednisolone kinetics in children receiving anticonvulsant therapy." Clin Pharmacol Ther, 42, p. 424-32
  2. Gambertoglio JG, Holford NH, Kapusnik JE, et al. (1984) "Disposition of total and unbound prednisolone in renal transplant patients receiving anticonvulsants." Kidney Int, 25, p. 119-23
  3. Sehgal VN, Srivastava G (1988) "Corticosteroid-unresponsive pemphigus vulgaris following antiepileptic therapy." Int J Dermatol, 27, p. 258
  4. Brooks PM, Buchanan WW, Grove M, Downie WW (1976) "Effects of enzyme induction on metabolism of prednisolone." Ann Rheum Dis, 35, p. 339-43
  5. Hancock KW, Levell MJ (1978) "Primidone/dexamethasone interaction." Lancet, 2, p. 97-8
  6. Young MC, Hughes IA (1991) "Loss of therapeutic control in congenital adrenal hyperplasia due to interaction between dexamethasone and primidone." Acta Paediatr Scand, 80, p. 120-4
  7. Stjernholm MR, Katz FH (1975) "Effects of diphenylhydantoin, phenobarbital, and diazepam on the metabolism of methylprednisolone and its sodium succinate." J Clin Endocrinol Metab, 41, p. 887-93
  8. (2001) "Product Information. Phenobarbital (phenobarbital)." Lilly, Eli and Company
  9. Brooks SM, Werk EE, Ackerman SJ, Sullivan I, Thrasher K (1972) "Adverse effects of phenobarbital on corticosteroid metabolism in patients with bronchial asthma." N Engl J Med, 286, p. 1125-8
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics."
Moderate

hydrocortisone aminophylline

Applies to: hydrocortisone and aminophylline / ephedrine / guaifenesin / phenobarbital

MONITOR: The concomitant use of theophylline and corticosteroids may theoretically increase the risk of hypokalemia due to additive potassium-lowering effects. Additionally, theophylline serum concentrations may be altered. The mechanism is unknown and data have been limited and conflicting; increased, decreased, and unchanged theophylline levels have all been reported.

MANAGEMENT: Monitoring for altered efficacy and safety of theophylline and altered serum potassium and theophylline concentrations is advisable when these drugs are coadministered. Patients should be advised to notify their physician if they experience signs of hypokalemia (e.g., weakness, lethargy, and muscle pains or cramps), worsening respiratory symptoms, or signs of theophylline toxicity (e.g., nausea, vomiting, diarrhea, headache, restlessness, insomnia, or irregular heartbeat).

References (6)
  1. Fergusson RJ, Scott CM, Rafferty P, Gaddie J (1987) "Effect of prednisolone on theophylline pharmacokinetics in patients with chronic airflow obstruction." Thorax, 42, p. 195-8
  2. Anderson JL, Ayres JW, Hall CA (1984) "Potential pharmacokinetic interaction between theophylline and prednisone." Clin Pharm, 3, p. 187-8
  3. Buchanan N, Hurwitz S, Butler P (1979) "Asthma - a possible interaction between hydrocortisone and theophylline." S Afr Med J, 56, p. 1147-8
  4. Elvey SM, Saccar CL, Rocci ML, Mansmann HC, Martynec DM, Kester MB (1986) "The effect of corticosteroids on theophylline metabolim in asthmatic children." Ann Allergy, 56, p. 520
  5. Tatsis G, Orphanidou D, Douratsos D, et al. (1991) "The effect of steroids on theophylline absorption." J Int Med Res, 19, p. 326-9
  6. Leavengood DC, Bunker-Soler AL, Nelson HS (1983) "The effect of corticosteroids on theophylline metabolism." Ann Allergy, 50, p. 249-51
Moderate

PHENobarbital aminophylline

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

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

ePHEDrine aminophylline

Applies to: aminophylline / ephedrine / guaifenesin / phenobarbital and aminophylline / 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 (5)
  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

Drug and food interactions

Major

PHENobarbital food

Applies to: aminophylline / 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 (5)
  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
Moderate

ePHEDrine food

Applies to: aminophylline / 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 (7)
  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
Moderate

aminophylline food

Applies to: aminophylline / 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 (7)
  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

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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