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Drug Interactions between levofloxacin and Marax

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

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Interactions between your drugs

Moderate

hydrOXYzine levoFLOXacin

Applies to: Marax (ephedrine / hydroxyzine / theophylline) and levofloxacin

MONITOR: Certain quinolones, including levofloxacin, norfloxacin, and ofloxacin, may cause dose-related prolongation of the QT interval in some patients. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. During postmarketing surveillance, rare cases of torsade de pointes and ventricular tachycardia have been reported in patients taking levofloxacin, norfloxacin, and ofloxacin. The levofloxacin cases primarily involved patients with underlying medical conditions or taking concomitant medications that may have been contributory. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Although the risk of a serious interaction is probably low, caution is recommended if levofloxacin, norfloxacin, or ofloxacin is used in combination with other drugs that can prolong the QT interval. Since the magnitude of QTc prolongation increases with increasing plasma concentrations of the quinolone, recommended dosages and intravenous infusion rates should not be exceeded. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. "Product Information. Floxin (ofloxacin)." Ortho McNeil Pharmaceutical PROD (2001):
  2. Thomas M, Maconochie JG, Fletcher E "The dilemma of the prolonged QT interval in early drug studies." Br J Clin Pharmacol 41 (1996): 77-81
  3. "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical PROD (2001):
  4. Samaha FF "QTC interval prolongation and polymorphic ventricular tachycardia in association with levofloxacin." Am J Med 107 (1999): 528-9
  5. Iannini PB, Doddamani S, Byazrova E, Curciumaru I, Kramer H "Risk of torsades de pointes with non-cardiac drugs. Prolongation of QT interval is probably a class effect of fluoroquinolones." Br Med J 322 (2001): 46-7
  6. Owens RC "Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes." Pharmacotherapy 21 (2001): 301-19
  7. Ball P "Quinolone-induced QT interval prolongation: a not-so-unexpected class effect." J Antimicrob Chemother 45 (2000): 557-9
  8. Kang J, Wang L, Chen XL, Triggle DJ, Rampe D "Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG." Mol Pharmacol 59 (2001): 122-6
  9. Kahn JB "Latest industry information on the safety profile of levofloxacin in the US." Chemotherapy 47 Suppl 3 (2001): 32-7
  10. Frothingham R "Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin." Pharmacotherapy 21 (2001): 1468-72
  11. Oliphant CM, Green GM "Quinolones: a comprehensive review." Am Fam Physician 65 (2002): 455-64
  12. Owens RC Jr, Ambrose PG "Torsades de pointes associated with fluoroquinolones." Pharmacotherapy 22 (2002): 663-8; discussion 668-72
  13. Noel GJ, Natarajan J, Chien S, Hunt TL, Goodman DB, Abels R "Effects of three fluoroquinolones on QT interval in healthy adults after single doses." Clin Pharmacol Ther 73 (2003): 292-303
  14. Iannini PB "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf 1 (2002): 121-8
  15. Owens RC "QT Prolongation with Antimicrobial Agents : Understanding the Significance." Drugs 64 (2004): 1091-124
  16. Nykamp DL, Blackmon CL, Schmidt PE, Roberson AG "QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine." Ann Pharmacother 39 (2005): 543-6
  17. Katritsis D, Camm AJ "Quinolones: cardioprotective or cardiotoxic." Pacing Clin Electrophysiol 26 (2003): 2317-20
  18. Stahlmann R "Clinical toxicological aspects of fluoroquinolones." Toxicol Lett 127 (2002): 269-77
  19. Makaryus AN, Byrns K, Makaryus MN, Natarajan U, Singer C, Goldner B "Effect of ciprofloxacin and levofloxacin on the QT interval: is this a significant "clinical" event?" South Med J 99 (2006): 52-6
  20. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  21. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  22. Falagas ME, Rafailidis PI, Rosmarakis ES "Arrhythmias associated with fluoroquinolone therapy." Int J Antimicrob Agents 29 (2007): 374-9
  23. Cerner Multum, Inc. "Australian Product Information." O 0
View all 23 references

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Minor

theophylline ePHEDrine

Applies to: Marax (ephedrine / hydroxyzine / theophylline) and Marax (ephedrine / hydroxyzine / 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

Moderate

theophylline food

Applies to: Marax (ephedrine / hydroxyzine / 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

hydrOXYzine food

Applies to: Marax (ephedrine / hydroxyzine / theophylline)

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

levoFLOXacin food

Applies to: levofloxacin

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of levofloxacin. According to the drug product labeling, administration of levofloxacin 500 mg with food prolonged the time to peak concentration by 1 hour and decreased the Cmax decreased by 25% following administration of the oral solution and by 14% following administration of the oral tablet.

MANAGEMENT: To ensure maximal and consistent oral absorption, levofloxacin oral solution should be taken at least one hour before or two hours after meals. For administration of the oral solution with continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for one hour before and two hours after the dose of levofloxacin. The oral tablets may be taken without regard to food.

References

  1. 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: Marax (ephedrine / hydroxyzine / 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: Marax (ephedrine / hydroxyzine / 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.

Further information

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