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Drug Interactions between Ami-rax and linezolid

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

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Major

ePHEDrine linezolid

Applies to: Ami-rax (ephedrine / hydroxyzine / theophylline) and linezolid

CONTRAINDICATED: Linezolid may potentiate the pressor response to sympathomimetic agents. Linezolid is a reversible, nonselective monoamine oxidase inhibitor (MAOI) and, as such, may enhance sympathomimetic effect by increasing norepinephrine storage in adrenergic neurons. The interaction may be more likely to occur with indirect- or mixed-acting sympathomimetics such as pseudoephedrine or ephedrine than with direct-acting agents like epinephrine, norepinephrine, and isoproterenol. In healthy normotensive subjects, coadministration of linezolid (600 mg every 12 hours for 3 days) and two doses of pseudoephedrine (60 mg each) or phenylpropanolamine (25 mg each) given 4 hours apart resulted in a mean maximum increase in systolic blood pressure of 32 mmHg and 38 mmHg, respectively, compared to baseline. The mean maximum systolic blood pressure during coadministration was also significantly increased compared to either agent alone. Heart rate was not affected. Maximum blood pressure levels were seen 2 to 3 hours after the second dose of phenylpropanolamine or pseudoephedrine, and returned to baseline 2 to 3 hours after peak.

MANAGEMENT: Unless blood pressure and clinical status can be closely monitored, linezolid should not be administered in combination with direct- or indirect-acting sympathomimetic agents (e.g., pseudoephedrine, phenylpropanolamine), vasopressive agents (e.g., epinephrine, norepinephrine), or dopaminergic agents (e.g., dopamine, dobutamine). If the combination is used, lower initial dosages of adrenergic agents such as dopamine or epinephrine are recommended, with careful titration to the desired response.

References

  1. "Product Information. Zyvox (linezolid)." Pharmacia and Upjohn PROD (2001):
  2. Hendershot PE, Antal EJ, Welshman IR, Batts DH, Hopkins NK "Linezolid: pharmacokinetic and pharmacodynamic evaluation of coadministration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorpan HBr." J Clin Pharmacol 41 (2001): 563-72

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Moderate

hydrOXYzine linezolid

Applies to: Ami-rax (ephedrine / hydroxyzine / theophylline) and linezolid

GENERALLY AVOID: Coadministration of monoamine oxidase inhibitors (MAOIs) and antihistamines may result in additive central nervous system depressant effects. In addition, limited data suggest that MAOIs may potentiate and prolong the anticholinergic effects of antihistamines due to inhibition of catecholamine degradation, which may lead to overstimulation of the sympathetic nervous system. In one published report, a woman who had been on phenelzine 30 mg/day for six months developed irritability and visual hallucinations two months following the addition of cyproheptadine 2 mg at bedtime to treat phenelzine-induced anorgasmia. The hallucinations cleared over 48 hours following the discontinuation of her medications. In another published report, a patient developed delirium with symptoms of aggression, paranoia, and vivid auditory as well as visual hallucinations after two days of receiving diphenhydramine 300 mg/day and linezolid 600 mg every 12 hours. The patient also had tachycardia, very warm skin, and possibly blurred vision (as evidenced by constant squinting). Central anticholinergic intoxication and dopaminergic hyperactivity were suspected. Symptoms subsided over four days following the discontinuation of diphenhydramine, while linezolid was continued with no subsequent sequelae. In a third report, a patient developed visual hallucinations associated with confusion and disorientation after nine days of linezolid and antihistamine therapy, including dexchlorpheniramine and cetirizine for the first four days and hydroxyzine for the next five. Physical examination did not reveal any focal neurological signs, myoclonus or ataxia, and cerebral CT scan and EEG were within normal limits. Symptoms resolved two days after linezolid was discontinued.

MANAGEMENT: Prescribing antihistamines in combination with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, procarbazine) should generally be avoided. If concomitant treatment is unavoidable, patients should be counseled to avoid hazardous activities requiring 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. It may be appropriate to monitor some patients for increased anticholinergic effects (e.g., constipation, urinary retention, fever, heat intolerance, blurred vision, confusion, hallucinations, dizziness, palpitations, arrhythmias, syncope), since certain populations such as the elderly and those with underlying organic brain disease tend to be more sensitive to these effects and may be susceptible to anticholinergic intoxication. It should be noted that the manufacturers of many of the sedating antihistamines (e.g., chlorpheniramine, dexchlorpheniramine, diphenhydramine, pheniramine, promethazine) consider their use within 14 days of MAOIs to be contraindicated.

References

  1. Kahn DA "Possible toxic interaction between cyproheptadine and phenelzine." Am J Psychiatry 144 (1987): 1242-3
  2. "Product Information. Periactin (cyproheptadine)." Merck & Co., Inc PROD (2002):
  3. "Product Information. Benadryl (diphenhydramine)." Parke-Davis PROD (2002):
  4. "Product Information. Matulane (procarbazine)." Roche Laboratories PROD (2001):
  5. Serio RN "Acute delirium associated with combined diphenhydramine and linezolid use." Ann Pharmacother 38 (2004): 62-5
  6. Ferry T, Ponceau B, Simon M, et al. "Possibly linezolid-induced peripheral and central neurotoxicity: report of four cases." Infection 33 (2005): 151-4
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  8. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  9. Cerner Multum, Inc. "Australian Product Information." O 0
View all 9 references

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Minor

theophylline ePHEDrine

Applies to: Ami-rax (ephedrine / hydroxyzine / theophylline) and Ami-rax (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

Major

linezolid food

Applies to: linezolid

CONTRAINDICATED: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase inhibitors (MAOIs). The mechanism is inhibition of MAO-A, the enzyme responsible for metabolizing exogenous amines such as tyramine in the gut and preventing them from being absorbed intact. Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules.

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

MANAGEMENT: In general, patients treated with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, procarbazine) should avoid consumption of products that contain large amounts of amines and protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, salamis, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, sauerkraut, yogurt, papaya products, meat tenderizers, fava bean pods, protein extracts, yeast extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. At least 14 days should elapse following discontinuation of MAOI therapy before these foods may be consumed. Specially designed reference materials and dietary consultation are recommended so that an appropriate and safe diet can be planned. Patients should be advised to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, difficulty thinking, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. Patients should also be counseled not to use MAOIs with alcohol, and to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them.

References

  1. Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7
  2. Goldberg LI "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA 190 (1964): 456-62
  3. Nuessle WF, Norman FC, Miller HE "Pickled herring and tranylcypromine reaction." JAMA 192 (1965): 142-3
  4. Sweet RA, Liebowitz MR, Holt CS, Heimberg RG "Potential interactions between monoamine oxidase inhibitors and prescribed dietary supplements." J Clin Psychopharmacol 11 (1991): 331-2
  5. Walker JI, Davidson J, Zung WWK "Patient compliance with MAO Inhibitor therapy." J Clin Psychiatry 45 (1984): 78-80
  6. Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6
  7. Darcy PF, Griffin JP "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev 14 (1995): 211-31
  8. Maxwell MB "Reexamining the dietary restrictions with procarbazine (an MAOI)." Cancer Nurs 3 (1980): 451-7
  9. "Product Information. Matulane (procarbazine)." Roche Laboratories PROD (2001):
  10. De Vita VT, Hahn MA, Oliverio VT "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med 120 (1965): 561-5
  11. Zetin M, Plon L, DeAntonio M "MAOI reaction with powdered protein dietary supplement." J Clin Psychiatry 48 (1987): 499
  12. Domino EF, Selden EM "Red wine and reactions." J Clin Psychopharmacol 4 (1984): 173-4
  13. Tailor SA, Shulman KI, Walker SE, Moss J, Gardner D "Hypertensive episode associated with phenelzine and tap beer--a reanalysis of the role of pressor amines in beer." J Clin Psychopharmacol 14 (1994): 5-14
  14. Pohl R, Balon R, Berchou R "Reaction to chicken nuggets in a patient taking an MAOI." Am J Psychiatry 145 (1988): 651
  15. "Product Information. Furoxone (furazolidone)." Roberts Pharmaceutical Corporation PROD (2001):
  16. "Product Information. Nardil (phenelzine)." Parke-Davis PROD (2001):
  17. "Product Information. Marplan (isocarboxazid)." Roche Laboratories PROD (2001):
  18. "Product Information. Zyvox (linezolid)." Pharmacia and Upjohn PROD (2001):
  19. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
View all 19 references

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Moderate

theophylline food

Applies to: Ami-rax (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: Ami-rax (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

theophylline food

Applies to: Ami-rax (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: Ami-rax (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.

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