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Drug Interactions between duloxetine and KG-Tuss HD

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

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Interactions between your drugs

Moderate

pseudoephedrine DULoxetine

Applies to: KG-Tuss HD (guaifenesin / hydrocodone / pseudoephedrine) and duloxetine

MONITOR: Additive or synergistic effects on blood pressure and heart rate may occur when serotonin-norepinephrine reuptake inhibitors (SNRIs) are combined with sympathomimetic agents such as nasal decongestants, adrenergic bronchodilators, ophthalmic vasoconstrictors, and systemic vasopressors. The use of SNRIs alone has been associated with sustained increases in blood pressure and heart rate, and cases of elevated blood pressure requiring immediate treatment have been reported in postmarketing experience.

MANAGEMENT: Caution is advised if SNRIs are used with other drugs that can increase blood pressure and/or heart rate. Blood pressure and pulse should be measured prior to initiating SNRI therapy and monitored at regular intervals thereafter. Dose reduction or discontinuation of the SNRI should be considered in patients who experience a sustained increase in blood pressure or pulse rate.

References

  1. (2001) "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories
  2. (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company
  3. (2008) "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories
  4. (2009) "Product Information. Savella (milnacipran)." Forest Pharmaceuticals
  5. (2009) "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals
  6. (2013) "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals
View all 6 references

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Moderate

HYDROcodone DULoxetine

Applies to: KG-Tuss HD (guaifenesin / hydrocodone / pseudoephedrine) and duloxetine

MONITOR: Opioids may potentiate the effects of serotonergic agents and increase the risk of serotonin syndrome. The interaction has primarily been reported with the phenylpiperidine opioids (e.g., meperidine, fentanyl) and tramadol, which are known to possess some serotonergic activity, although a few cases have involved other opioids such as oxycodone, methadone, morphine, hydromorphone, codeine, and buprenorphine. Serotonin syndrome 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, 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. Since many serotonergic agents can also cause central nervous system depression, concomitant use with opioids may result in increased sedation and impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Caution is advised when opioids are used concomitantly with serotonergic agents such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), other antidepressants/psychotropic agents (e.g., amoxapine, buspirone, lithium, maprotiline, mirtazepine, nefazodone, trazodone, vilazodone), 5-HT1 receptor agonists (triptans), 5-HT3 receptor antagonists, cyclobenzaprine, dextromethorphan, 5-hydroxytryptophan, and St. John's wort. Patients should be monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. 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. Patients should also be advised of potentially additive central nervous system effects from these agents and to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them.

References

  1. Meyer D, Halfin V (1981) "Toxicity secondary to meperidine in patients on monoamine oxidase inhibitors: a case report and critical review." J Clin Psychopharmacol, 1, p. 319-21
  2. Zornberg GL, Bodkin JA, Cohen BM (1991) "Severe adverse interaction between pethidine and selegiline." Lancet, 337, p. 246
  3. Hansen TE, Dieter K, Keepers GA (1990) "Interaction of fluoxetine and pentazocine." Am J Psychiatry, 147, p. 949-50
  4. Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
  5. Noble WH, Baker A (1992) "MAO inhibitors and coronary artery surgery: a patient death." Can J Anaesth, 39, p. 1061-6
  6. Insler SR, Kraenzler EJ, Licina MG, Savage RM, Starr NJ (1994) "Cardiac surgery in a patient taking monoamine oxidase inhibitors - an adverse fentanyl reaction." Anesth Analg, 78, p. 593-7
  7. Mason BJ, Blackburn KH (1997) "Possible serotonin syndrome associated with tramadol and sertraline coadministration." Ann Pharmacother, 31, p. 175-7
  8. Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
  9. 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
  10. Egberts AC, ter Borg J, Brodie-Meijer CC (1997) "Serotonin syndrome attributed to tramadol addition to paroxetine therapy." Int Clin Psychopharmacol, 12, p. 181-2
  11. Rosebraugh CJ, floxkhart DA, Yasuda SU, Woosley RL (2001) "Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient." J Clin Pharmacol, 41, p. 224-7
  12. Lange-Asschenfeldt C, Weigmann H, Hiemke C, Mann K (2002) "Serotonin syndrome as a result of fluoxetine in a patient with tramadol abuse: plasma level-correlated symptomatology." J Clin Psychopharmacol, 22, p. 440-1
  13. Kesavan S, Sobala GM (1999) "Serotonin syndrome with fluoxetine plus tramadol." J R Soc Med, 92, p. 474-5
  14. Gonzalez-Pinto A, Imaz H, De Heredia JL, Gutierrez M, Mico JA (2001) "Mania and tramadol-fluoxetine combination." Am J Psychiatry, 158, p. 964-5
  15. Dougherty JA, Young H, Shafi T (2002) "Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine." Ann Pharmacother, 36, p. 1647-1648
  16. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
  17. Tissot TA (2003) "Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use." Anesthesiology, 98, p. 1511-1512
  18. Roy S, Fortier LP (2003) "Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafexine." Can J Anaesth, 50, p. 32-5
  19. Gillman PK (1995) "Possible serotonin syndrome with moclobemide and pethidine." Med J Aust, 162, p. 554
  20. Houlihan DJ (2004) "Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine." Ann Pharmacother, 38, p. 411-3
  21. (2004) "Venlafaxine + tramadol: serotonin syndrome." Prescrire Int, 13, p. 57
  22. Mahlberg R, Kunz D, Sasse J, Kirchheiner J (2004) "Serotonin syndrome with tramadol and citalopram." Am J Psychiatry, 161, p. 1129
  23. Mittino D, Mula M, Monaco F (2004) "Serotonin syndrome associated with tramadol-sertraline coadministration." Clin Neuropharmacol, 27, p. 150-1
  24. Lantz MS, Buchalter EN, Giambanco V (1998) "Serotonin syndrome following the administration of tramadol with paroxetine." Int J Geriatr Psychiatry, 13, p. 343-5
  25. Gillman PK (2005) "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth
  26. Kitson R, Carr B (2005) "Tramadol and severe serotonin syndrome." Anaesthesia, 60, p. 934-5
  27. Gnanadesigan N, Espinoza RT, Smith R, Israel M, Reuben DB (2005) "Interaction of serotonergic antidepressants and opioid analgesics: Is serotonin syndrome going undetected?" J Am Med Dir Assoc, 6, p. 265-9
  28. 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
  29. Ailawadhi S, Sung KW, Carlson LA, Baer MR (2007) "Serotonin syndrome caused by interaction between citalopram and fentanyl." J Clin Pharm Ther, 32, p. 199-202
  30. Vizcaychipi MP, Walker S, Palazzo M (2007) "Serotonin syndrome triggered by tramadol." Br J Anaesth, 99, p. 919
  31. Das PK, Warkentin DI, Hewko R, Forrest DL (2008) "Serotonin syndrome after concomitant treatment with linezolid and meperidine." Clin Infect Dis, 46, p. 264-5
  32. Rang ST, Field J, Irving C (2008) "Serotonin toxicity caused by an interaction between fentanyl and paroxetine." Can J Anaesth, 55, p. 521-5
  33. Guo SL, Wu TJ, Liu CC, Ng CC, Chien CC, Sun HL (2009) "Meperidine-induced serotonin syndrome in a susceptible patient." Br J Anaesth
  34. Davis JJ, Buck NS, Swenson JD, Johnson KB, Greis PE (2013) "Serotonin syndrome manifesting as patient movement during total intravenous anesthesia with propofol and remifentanil." J Clin Anesth, 25, p. 52-4
  35. Hillman AD, Witenko CJ, Sultan SM, Gala G (2015) "Serotonin syndrome caused by fentanyl and methadone in a burn injury." Pharmacotherapy, 35, p. 112-7
  36. Mateo-Carrasco H, Munoz-Aguilera EM, Garcia-Torrecillas JM, Abu Al-Robb H (2015) "Serotonin syndrome probably triggered by a morphine-phenelzine interaction." Pharmacotherapy, 35, e102-5
  37. Abadie D, Rousseau V, Logerot S, Cottin J, Montastruc JL, Montastruc F (2015) "Serotonin Syndrome: Analysis of Cases Registered in the French Pharmacovigilance Database." J Clin Psychopharmacol
  38. Shakoor M, Ayub S, Ahad A, Ayub Z (2014) "Transient serotonin syndrome caused by concurrent use of tramadol and selective serotonin reuptake inhibitor." Am J Case Rep, 15, p. 562-4
  39. Larson KJ, Wittwer ED, Nicholson WT, Weingarten TN, Price DL, Sprung J (2015) "Myoclonus in patient on fluoxetine after receiving fentanyl and low-dose methylene blue during sentinel lymph node biopsy." J Clin Anesth, 27, p. 247-51
  40. US Food and Drug Administration (FDA) (2018) FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM491302.pdf
View all 40 references

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Drug and food interactions

Major

HYDROcodone food

Applies to: KG-Tuss HD (guaifenesin / hydrocodone / pseudoephedrine)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including hydrocodone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Consumption of alcohol while taking some sustained-release formulations of hydrocodone may cause rapid release of the drug, resulting in high systemic levels of hydrocodone that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. In study subjects, the rate of absorption of hydrocodone from an extended-release formulation was found to be affected by coadministration with 40% alcohol in the fasted state, as demonstrated by an average 2.4-fold (up to 3.9-fold in one subject) increase in hydrocodone peak plasma concentration and a decrease in the time to peak concentration. Alcohol also increased the extent of absorption by an average of 1.2-fold (up to 1.7-fold in one subject).

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of hydrocodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of hydrocodone by certain compounds present in grapefruit. Increased hydrocodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.

MANAGEMENT: Patients taking sustained-release formulations of hydrocodone should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as hydrocodone should not be combined with alcohol. Patients should also avoid consumption of grapefruit or grapefruit juice during treatment with hydrocodone.

References

  1. (2013) "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc

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Moderate

DULoxetine food

Applies to: duloxetine

GENERALLY AVOID: Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

MANAGEMENT: Due to the risk of liver injury, patients prescribed duloxetine should be counseled to avoid excessive use of alcohol. Duloxetine should generally not be prescribed to patients with substantial alcohol use.

References

  1. (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company

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Moderate

pseudoephedrine food

Applies to: KG-Tuss HD (guaifenesin / hydrocodone / pseudoephedrine)

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.