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Drug Interactions between Equetro and Tedrigen

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

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Interactions between your drugs

Moderate

carBAMazepine theophylline

Applies to: Equetro (carbamazepine) and Tedrigen (ephedrine / phenobarbital / theophylline)

MONITOR: Carbamazepine may decrease theophylline serum levels. Also, theophyllines may decrease serum levels and effects of carbamazepine. The mechanisms may be related to induction of hepatic CYP450 metabolism.

MANAGEMENT: Close observation for clinical and laboratory evidence of altered effects is recommended for both agents. Patients should be advised to notify their physician if they experience loss of therapeutic effects.

References

  1. Upton RA "Pharmacokinetic interactions between theophylline and other medication (Part I)." Clin Pharmacokinet 20 (1991): 66-80
  2. Rosenberry KR, Defusco CJ, Mansmann HC, McGeady SJ "Reduced theophylline half-life induced by carbamazepine therapy." J Pediatr 102 (1983): 472-4
  3. Mitchell EA "Interaction between carbamazinepine and theophylline." N Z Med J 1 (1986): 69-70

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Moderate

theophylline PHENobarbital

Applies to: Tedrigen (ephedrine / phenobarbital / theophylline) and Tedrigen (ephedrine / phenobarbital / 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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Minor

carBAMazepine PHENobarbital

Applies to: Equetro (carbamazepine) and Tedrigen (ephedrine / phenobarbital / theophylline)

Coadministration with a barbiturate may decrease the plasma concentrations of carbamazepine and increase concentrations of its active 10,11-epoxide metabolite. The mechanism is barbiturate induction of CYP450 3A4, the isoenzyme responsible for the metabolism of carbamazepine to carbamazepine-10,11-epoxide (CBZ-E). In clinical and pharmacokinetic studies, carbamazepine levels were typically lower when the drug was administered with phenobarbital than when administered alone, and CBZ-E levels generally higher. However, one study reported an increased clearance and reduced half-life of single-dose CBZ-E in six epileptic patients who were receiving phenobarbital compared to six drug-free healthy volunteers, which would seem to suggest an induction of CBZ-E metabolism also. The clinical significance of these changes are unknown, particularly since the anticonvulsant activity of CBZ-E relative to the parent compound has not been established. Until more data are available, it may be reasonable to monitor serum carbamazepine levels more closely whenever a barbiturate (if used for more than a few days) is added to or withdrawn from therapy.

References

  1. Dam M, Jensen A, Christiansen J "Plasma level and effect of carbamazepine in grand mal and psychomotor epilepsy." Acta Neurol Scand S75 (1975): 33-8
  2. Eichelbaum M, Kothe KW, Hoffmann F, von Unruh GE "Kinetics and metabolism of carbamazepine during combined antiepileptic drug therapy." Clin Pharmacol Ther 26 (1979): 366-71
  3. Ramsay RE, McManus DQ, Guterman A, et al. "Carbamazepine metabolism in humans: effect of concurrent anticonvulsant therapy." Ther Drug Monit 12 (1990): 235-41
  4. Cereghino JJ, Brock JT, Van Meter JC, et al. "The efficacy of carbamazepine combinations in epilepsy." Clin Pharmacol Ther 18 (1975): 733-41
  5. Spina E, Martines C, Fazio A, Trio R, Pisani F, Tomson T "Effect of phenobarbital on the pharmacokinetics of carbamazepine-10, 11-epoxide, an active metabolite of carbamazepine." Ther Drug Monit 13 (1991): 109-12
  6. "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals PROD (2002):
  7. Tomson T, Spina E, Wedlund JE "Minor additive inducing effects of phenobarbital on carbamazepine clearance in patients on combined carbamazepine-phenytoin therapy." Ther Drug Monit 9 (1987): 117-9
  8. Benetello P, Furlanut M "Primidone-carbamazepine interaction: clinical consequences." Int J Clin Pharmacol Res 7 (1987): 165-8
  9. Liu H, Delgado MR "Interactions of phenobarbital and phenytoin with carbamazepine and its metabolites' concentrations, concentration ratios, and level dose ratios in epileptic children." Epilepsia 36 (1995): 249-54
View all 9 references

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Minor

theophylline ePHEDrine

Applies to: Tedrigen (ephedrine / phenobarbital / theophylline) and Tedrigen (ephedrine / phenobarbital / 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: Tedrigen (ephedrine / phenobarbital / 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

carBAMazepine food

Applies to: Equetro (carbamazepine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

References

  1. "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals PROD (2002):
  2. Garg SK, Kumar N, Bhargava VK, Prabhakar SK "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther 64 (1998): 286-8
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77

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Moderate

theophylline food

Applies to: Tedrigen (ephedrine / phenobarbital / 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: Tedrigen (ephedrine / phenobarbital / 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: Tedrigen (ephedrine / phenobarbital / 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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