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Drug Interactions between dihydroergotamine and G-Tusicof

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

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Major

dextromethorphan dihydroergotamine

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

MONITOR CLOSELY: Concomitant use of agents with serotonergic activity such as serotonin reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, 5-HT1 receptor agonists, ergot alkaloids, cyclobenzaprine, lithium, St. John's wort, phenylpiperidine opioids, dextromethorphan, and tryptophan may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, 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.

MANAGEMENT: In general, the concomitant use of multiple serotonergic agents should be avoided if possible, or otherwise approached with caution if potential benefit is deemed to outweigh the risk. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. The potential risk for serotonin syndrome should be considered even when administering serotonergic agents sequentially, as some agents may demonstrate a prolonged elimination half-life. For example, some experts suggest a 5-week washout period following use of fluoxetine and 3 weeks following the use of vortioxetine before administering another serotonergic agent. Individual product labeling for washout periods should be consulted for current recommendations. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures.

References

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  53. Smith DL, Wenegrat BG (2000) "A case report of serotonin syndrome associated with combined nefazodone and fluoxetine." J Clin Psychiatry, 61, p. 146
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  56. Duggal HS, Fetchko J (2002) "Serotonin syndrome and atypical antipsychotics." Am J Psychiatry, 159, p. 672-3
  57. Wigen CL, Goetz MB (2002) "Serotonin syndrome and linezolid." Clin Infect Dis, 34, p. 1651-2
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  64. Lane R, Baldwin D (1997) "Selective serotonin reuptake inhibitor--induced serotonin syndrome: review." J Clin Psychopharmacol, 17, p. 208-21
  65. Bernard L, Stern R, Lew D, Hoffmeyer P (2003) "Serotonin syndrome after concomitant treatment with linezolid and citalopram." Clin Infect Dis, 36, p. 1197
  66. Dannawi M (2002) "Possible serotonin syndrome after combination of buspirone and St John's Wort." J Psychopharmacol, 16, p. 401
  67. Tissot TA (2003) "Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use." Anesthesiology, 98, p. 1511-1512
  68. 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
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  70. Roy S, Fortier LP (2003) "Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafexine." Can J Anaesth, 50, p. 32-5
  71. Giese SY, Neborsky R (2001) "Serotonin syndrome: potential consequences of Meridia combined with Demerol or fentanyl." Plast Reconstr Surg, 107, p. 293-4
  72. 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
  73. 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
  74. (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company
  75. Thomas CR, Rosenberg M, Blythe V, Meyer WJ 3rd (2004) "Serotonin syndrome and linezolid." J Am Acad Child Adolesc Psychiatry, 43, p. 790
  76. Boyer EW, Shannon M (2005) "The serotonin syndrome." N Engl J Med, 352, p. 1112-20
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  78. Morales N, Vermette H (2005) "Serotonin syndrome associated with linezolid treatment after discontinuation of fluoxetine." Psychosomatics, 46, p. 274-5
  79. Morales-Molina JA, Mateu-de Antonio J, Marin-Casino M, Grau S (2005) "Linezolid-associated serotonin syndrome: what we can learn from cases reported so far." J Antimicrob Chemother, 56, p. 1176-8
  80. DeBellis RJ, Schaefer OP, Liquori M, Volturo GA (2005) "Linezolid-associated serotonin syndrome after concomitant treatment with citalopram and mirtazepine in a critically ill bone marrow transplant recipient." J Intensive Care Med, 20, p. 351-3
  81. Hunter B, Kleinert MM, Osatnik J, Soria E (2006) "Serotonergic syndrome and abnormal ocular movements: worsening of rigidity by remifentanil?" Anesth Analg, 102, p. 1589
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  83. Strouse TB, Kerrihard TN, Forscher CA, Zakowski P (2006) "Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine." J Clin Psychopharmacol, 26, p. 681-683
  84. Keegan MT, Brown DR, Rabinstein AA (2006) "Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs." Anesth Analg, 103, p. 1466-8
  85. Paruchuri P, Godkar D, Anandacoomarswamy D, Sheth K, Niranjan S (2006) "Rare case of serotonin syndrome with therapeutic doses of paroxetine." Am J Ther, 13, p. 550-552
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  87. Packer S, Berman SA (2007) "Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid." Am J Psychiatry, 164, p. 346-7
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  91. Rang ST, Field J, Irving C (2008) "Serotonin toxicity caused by an interaction between fentanyl and paroxetine." Can J Anaesth, 55, p. 521-5
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  93. (2009) "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals
  94. Lee J, Franz L, Goforth HW (2009) "Serotonin syndrome in a chronic-pain patient receiving concurrent methadone, ciprofloxacin, and venlafaxine." Psychosomatics, 50, p. 638-9
  95. (2011) "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC
  96. Mugele J, Nanagas KA, Tormoehlen LM (2012) "Serotonin Syndrome Associated With MDPV Use: A Case Report." Ann Emerg Med
  97. (2012) "Product Information. Oleptro (trazodone)." Labopharm Inc
  98. (2013) "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals
  99. (2013) "Product Information. Brintellix (vortioxetine)." Takeda Pharmaceuticals America
  100. (2023) "Product Information. Exxua (gepirone)." Mission Pharmacal Company, 1
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Major

dihydroergotamine phenylephrine

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

CONTRAINDICATED: Additive or synergistic increases in blood pressure and/or ischemic response may occur when ergot alkaloids are combined with peripheral or central vasoconstrictors. Ergot alkaloids produce arterial vasoconstriction by stimulating alpha-adrenergic and serotonin receptors and inhibiting endothelial-derived relaxation factor release. There have been isolated case reports of gangrene in patients treated with intravenous ergonovine followed shortly by dopamine or norepinephrine.

MANAGEMENT: Concomitant use of dihydroergotamine with other vasoconstrictive agents is considered contraindicated by the manufacturer. Patients treated with dihydroergotamine should be advised to seek immediate medical attention if they experience potential symptoms of ischemia such as coldness, pallor, cyanosis, numbness, tingling, or pain in the extremities; muscle weakness; severe or worsening headache; visual disturbances; severe abdominal pain; chest pain; and shortness of breath.

References

  1. Buchanan N, Cane RD, Miller M (1977) "Symmetrical gangrene of the extremities associated with the use of dopamine subsequent to ergometrine administration." Intensive Care Med, 3, p. 55-6
  2. Barthel W, Glusa E, Koth W (1987) "Interactions of dihydroergotamine with etilefrine in human leg veins in vitro and in situ." Int J Clin Pharmacol Ther Toxicol, 25, p. 63-9
  3. (2002) "Product Information. D.H.E. 45 (dihydroergotamine)." Sandoz Pharmaceuticals Corporation
  4. Chuang SS (2003) "Finger ischemia secondary to the synergistic agonist effect of norepinephrine and ergonovine and in a burn patient." Burns, 29, p. 92-4
View all 4 references

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Drug and food interactions

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

dihydroergotamine food

Applies to: dihydroergotamine

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References

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  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  3. Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
  4. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  8. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  10. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  11. Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  13. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  14. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  19. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
  21. Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
  22. Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
  23. Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
  24. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
  25. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  26. Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
  28. Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
  29. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  30. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
  31. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
  32. Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
View all 32 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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Moderate

dihydroergotamine food

Applies to: dihydroergotamine

MONITOR: Nicotine may cause vasoconstriction in some patients and potentiate the ischemic response to ergot alkaloids.

MANAGEMENT: Caution may be advisable when ergot alkaloids are used in combination with nicotine products. Patients should be advised to seek immediate medical attention if they experience potential symptoms of ischemia such as coldness, pallor, cyanosis, numbness, tingling, or pain in the extremities; muscle weakness; severe or worsening headache; visual disturbances; severe abdominal pain; chest pain; and shortness of breath.

References

  1. (2001) "Product Information. Migranal (dihydroergotamine nasal)." Novartis Pharmaceuticals
  2. (2004) "Product Information. Cafergot (caffeine-ergotamine)." Novartis Pharmaceuticals
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."
View all 4 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.