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Drug Interactions between Folvite and Tedrigen

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

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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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Moderate

folic acid PHENobarbital

Applies to: Folvite (folic acid) and Tedrigen (ephedrine / phenobarbital / theophylline)

MONITOR: Anticonvulsants including, but not limited to, carbamazepine, lamotrigine, phenobarbital, phenytoin, primidone, and valproic acid have been shown to impair folate absorption and increase the metabolism of circulating folate. The precise mechanism of interaction has not been established.

MONITOR: Coadministration with folate therapy may reduce the anticonvulsant effects of phenytoin, phenobarbital, primidone, and succinimides. The exact mechanism of interaction is unknown. Available data pertain primarily to phenytoin. Some investigators suggest that folic acid may serve as a cofactor in the metabolism of phenytoin, thus clearance is increased in the presence of folic acid. In one study, administration of folic acid for 14 days reduced the serum levels of phenytoin in normal subjects without significantly altering the bound fraction. Urinary excretion of phenytoin and its metabolite, meta-hydroxydiphenylhydantoin, was increased. In another study, three of four folate-deficient male patients receiving phenytoin monotherapy for epilepsy demonstrated a 7.5% to 47.6% decrease in total phenytoin plasma concentration following the addition of folic acid 1 mg/day for 180 or 300 days. Ratios of urinary metabolites to parent drug increased in these patients, suggesting an increase in phenytoin oxidative metabolism. The interaction is further supported by case reports describing subtherapeutic phenytoin levels and/or breakthrough seizures following the addition of folate therapy, including one case involving folinic acid (leucovorin). Limited data are available for phenobarbital and primidone. In one study, the addition of folic acid 15 mg/day increased the frequency and severity of seizures in 13 of 26 folate-deficient epileptic patients receiving two or more anticonvulsant drugs, including phenytoin, phenobarbital, and primidone. Nine of them required discontinuation of folic acid therapy. No data are available for other hydantoins.

MANAGEMENT: Caution is advised when folate therapy is coadministered with anticonvulsants. Close monitoring for clinical and laboratory evidence of diminished therapeutic response to both treatments is recommended. Patients should be advised to notify their physician if they experience loss of seizure control.

References

  1. Furlanut M, Benetello P, Avogaro A, Dainese R "Effects of folic acid on phenytoin kinetics in healthy subjects." Clin Pharmacol Ther 24 (1978): 294-7
  2. Carl GF, Smith ML "Phenytoin-folate interactions: differing effects of the sodium salt and the free acid of phenytoin." Epilepsia 33 (1992): 372-5
  3. Berg MJ, Fincham RW, Ebert BE, Schottelius DD "Phenytoin pharmacokinetics: before and after folic acid administration." Epilepsia 33 (1992): 712-20
  4. MacCosbe PE, Toomey K "Interaction of phenytoin and folic acid." Clin Pharm 2 (1983): 362-9
  5. Robenberg IH "Drugs and folic acid absorption." Gastroenterology 63 (1972): 353-7
  6. Ch'ien LT, Krumdieck CL, Scott CW Jr, Butterworth CE Jr "Harmful effect of megadoses of vitamins: electroencephalogram abnormalities and seizures induced by intravenous folate in drug- treated epileptics." Am J Clin Nutr 28 (1975): 51-8
  7. Katz M "Potential danger of self-medication with folic acid." N Engl J Med 289 (1973): 1095
  8. Yuen GJ "Interaction of phenytoin and folic acid: an alternative explanation." Clin Pharm 3 (1984): 116,119
  9. Berg MJ, Rivey MP, Vern BA, Fischer LJ, Schottelius DD "Phenytoin and folic acid: individualized drug-drug interaction." Ther Drug Monit 5 (1983): 395-9
  10. Berg MJ, Fischer LJ, Rivey MP, Vern BA, Lantz RK, Schottelius DD "Phenytoin and folic acid interaction: a preliminary report." Ther Drug Monit 5 (1983): 389-94
  11. Berg MJ, Stumbo PJ, Chenard CA, Fincham RW, Schneider PJ, Schottelius D "Folic acid improves phenytoin pharmacokinetics." J Am Diet Assoc 95 (1995): 352-6
  12. Lewis DP, Van Dyke DC, Willhite LA, Stumbo PJ, Berg MJ "Phenytoin-folic acid interaction." Ann Pharmacother 29 (1995): 726-35
  13. "Product Information. Wellcovorin (leucovorin)." Glaxo Wellcome, Research Triangle Park, NC.
  14. Seligmann H, Potasman I, Weller B, Schwartz M, Prokocimer M "Phenytoin-folic acid interaction: A lesson to be learned." Clin Neuropharmacol 22 (1999): 268-72
  15. Veldhorst-Janssen NM, Boersma HH, de Krom MC, van Rijswijk RE "Oral tegafur/folinic acid chemotherapy decreases phenytoin efficacy." Br J Cancer 90 (2004): 745
  16. Steinweg DL, Bentley ML "Seizures following reduction in phenytoin level after orally administered folic acid." Neurology 64 (2005): 1982
  17. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  18. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  19. Cerner Multum, Inc. "Australian Product Information." O 0
  20. "Product Information. Levoleucovorin (levoleucovorin)." Spectrum Chemical (2008):
  21. 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):
  22. "Product Information. L-Methylfolate Calcium (l-methylfolate)." Virtus Pharmaceuticals LLC (2018):
View all 22 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

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

folic acid food

Applies to: Folvite (folic acid)

MONITOR: Ethanol may increase folic acid elimination and folic acid absorption is decreased in chronic alcoholics. Excessive alcohol consumption may lead to folate deficiency.

MANAGEMENT: Monitoring of patient response to folic acid supplementation if they also consume alcohol regularly may be recommended.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. 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):
  4. Cerner Multum, Inc "ANVISA Bulário Eletrônico." O 0 (2015):
  5. "Product Information. Folic Acid (folic acid)." Method Pharmaceuticals, LLC (2017):
View all 5 references

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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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