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Drug Interactions between G-Tusicof and linezolid

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

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Major

dextromethorphan linezolid

Applies to: G-Tusicof (dextromethorphan / guaifenesin / phenylephrine) and linezolid

CONTRAINDICATED: Coadministration of dextromethorphan with linezolid may increase the risk of serotonin syndrome, a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Dextromethorphan is a weak serotonin reuptake inhibitor whose serotonergic activity may be enhanced by monoamine oxidase inhibitors (MAOIs). Serious and fatal reactions have been reported, primarily with the antidepressant MAOIs. The risk should be lower with linezolid, a relatively weak, reversible MAOI. When linezolid (600 mg orally every 12 hours for 6 days) and dextromethorphan (20 mg orally twice, 4 hours apart, on days 4 and 6 of linezolid administration) were given to 14 healthy volunteers, no changes in mental status (sedation, performance testing) or autonomic function (blood pressure, heart rate, body temperature) were observed relative to administration of either linezolid or dextromethorphan alone. The conversion of dextromethorphan to its primary metabolite was reduced by linezolid, as evidenced by an approximately 30% decrease in dextrorphan peak plasma concentration (Cmax) and systemic exposure (AUC) during coadministration, but clinical significance is unknown. The investigators concluded that linezolid may be prescribed with dextromethorphan without restrictions. There have been no published reports of serotonin syndrome with the concomitant use of dextromethorphan and linezolid, although known cases have been associated individually with each during coadministration with other serotonergic agents. The British labeling for linezolid describes a postmarketing report of a patient experiencing serotonin syndrome-like effects during concurrent use of dextromethorphan that resolved upon discontinuation of both drugs.

MANAGEMENT: Due to the risk of serotonin syndrome, concomitant use of dextromethorphan with MAOIs is considered contraindicated by manufacturers of dextromethorphan-containing products. If coadministration with linezolid is required, patients should be monitored for the development of serotonin syndrome. Symptoms may include mental status changes such as irritability, altered consciousness, confusion, hallucinations, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

References

  1. Achamallah NS (1992) "Visual hallucinations after combining fluoxetine and dextromethorphan ." Am J Psychiatry, 149, p. 1406
  2. Bem JL, Peck R (1992) "Dextromethorphan. An overview of safety issues." Drug Saf, 7, p. 190-9
  3. Nierenberg DW, Semprebon M (1993) "The central nervous system serotonin syndrome." Clin Pharmacol Ther, 53, p. 84-8
  4. Rivers N, Horner B (1970) "Possible lethal reaction between nardil and dextromethorphan." Can Med Assoc J, 103, p. 85
  5. Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
  6. Cetaruk EW, Aaron CK (1994) "Hazards of nonprescription medications." Emerg Med Clin North Am, 12, p. 483-510
  7. Corkeron MA (1995) "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust, 163, p. 481-2
  8. Skop BP, Finkelstein JA, Mareth TR, Magoon MR, Brown TM (1994) "The serotonin syndrome associated wtih paroxetine, an over-the-counter cold remedy, and vascular disease." Am J Emerg Med, 12, p. 642-4
  9. Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
  10. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG (1998) "Serotonin syndrome resulting from drug interactions." Med J Aust, 169, p. 523-5
  11. (2001) "Product Information. Zyvox (linezolid)." Pharmacia and Upjohn
  12. Bernard SA, Bruera E (2000) "Drug interactions in palliative care." J Clin Oncol, 18, p. 1780-99
  13. Mackay FJ, Dunn NR, Mann RD (1999) "Antidepressants and the serotonin syndrome in general practice." Br J Gen Pract, 49, p. 871-4
  14. Hendershot PE, Antal EJ, Welshman IR, Batts DH, Hopkins NK (2001) "Linezolid: pharmacokinetic and pharmacodynamic evaluation of coadministration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorpan HBr." J Clin Pharmacol, 41, p. 563-72
  15. Wigen CL, Goetz MB (2002) "Serotonin syndrome and linezolid." Clin Infect Dis, 34, p. 1651-2
  16. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
  17. Lavery S, Ravi H, McDaniel WW, Pushkin YR (2001) "Linezolid and serotonin syndrome." Psychosomatics, 42, p. 432-4
  18. Bernard L, Stern R, Lew D, Hoffmeyer P (2003) "Serotonin syndrome after concomitant treatment with linezolid and citalopram." Clin Infect Dis, 36, p. 1197
  19. Hachem RY, Hicks K, Huen A, Raad I (2003) "Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients." Clin Infect Dis, 37, E8-E11
  20. Jones SL, Athan E, O'Brien D (2004) "Serotonin syndrome due to co-administration of linezolid and venlafaxine." J Antimicrob Chemother, 54, p. 289-90
  21. Tahir N (2004) "Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram." J Am Med Dir Assoc, 5, p. 111-3
  22. Cerner Multum, Inc. "UK Summary of Product Characteristics."
View all 22 references

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Major

phenylephrine linezolid

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

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

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Moderate

dextromethorphan food

Applies to: G-Tusicof (dextromethorphan / guaifenesin / phenylephrine)

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 (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

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Moderate

phenylephrine food

Applies to: G-Tusicof (dextromethorphan / guaifenesin / phenylephrine)

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 (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
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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.