Drug Interactions between methadone and Phanatuss
This report displays the potential drug interactions for the following 2 drugs:
- methadone
- Phanatuss (dextromethorphan/guaifenesin)
Interactions between your drugs
methadone dextromethorphan
Applies to: methadone and Phanatuss (dextromethorphan / guaifenesin)
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
- 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
- Zornberg GL, Bodkin JA, Cohen BM (1991) "Severe adverse interaction between pethidine and selegiline." Lancet, 337, p. 246
- Hansen TE, Dieter K, Keepers GA (1990) "Interaction of fluoxetine and pentazocine." Am J Psychiatry, 147, p. 949-50
- Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
- Noble WH, Baker A (1992) "MAO inhibitors and coronary artery surgery: a patient death." Can J Anaesth, 39, p. 1061-6
- 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
- Mason BJ, Blackburn KH (1997) "Possible serotonin syndrome associated with tramadol and sertraline coadministration." Ann Pharmacother, 31, p. 175-7
- Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
- 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
- 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
- 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
- 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
- Kesavan S, Sobala GM (1999) "Serotonin syndrome with fluoxetine plus tramadol." J R Soc Med, 92, p. 474-5
- 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
- Dougherty JA, Young H, Shafi T (2002) "Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine." Ann Pharmacother, 36, p. 1647-1648
- Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
- Tissot TA (2003) "Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use." Anesthesiology, 98, p. 1511-1512
- Roy S, Fortier LP (2003) "Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafexine." Can J Anaesth, 50, p. 32-5
- Gillman PK (1995) "Possible serotonin syndrome with moclobemide and pethidine." Med J Aust, 162, p. 554
- Houlihan DJ (2004) "Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine." Ann Pharmacother, 38, p. 411-3
- (2004) "Venlafaxine + tramadol: serotonin syndrome." Prescrire Int, 13, p. 57
- Mahlberg R, Kunz D, Sasse J, Kirchheiner J (2004) "Serotonin syndrome with tramadol and citalopram." Am J Psychiatry, 161, p. 1129
- Mittino D, Mula M, Monaco F (2004) "Serotonin syndrome associated with tramadol-sertraline coadministration." Clin Neuropharmacol, 27, p. 150-1
- Lantz MS, Buchalter EN, Giambanco V (1998) "Serotonin syndrome following the administration of tramadol with paroxetine." Int J Geriatr Psychiatry, 13, p. 343-5
- Gillman PK (2005) "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth
- Kitson R, Carr B (2005) "Tramadol and severe serotonin syndrome." Anaesthesia, 60, p. 934-5
- 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
- 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
- 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
- Vizcaychipi MP, Walker S, Palazzo M (2007) "Serotonin syndrome triggered by tramadol." Br J Anaesth, 99, p. 919
- 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
- Rang ST, Field J, Irving C (2008) "Serotonin toxicity caused by an interaction between fentanyl and paroxetine." Can J Anaesth, 55, p. 521-5
- Guo SL, Wu TJ, Liu CC, Ng CC, Chien CC, Sun HL (2009) "Meperidine-induced serotonin syndrome in a susceptible patient." Br J Anaesth
- 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
- 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
- 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
- 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
- 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
- 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
- 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
Drug and food interactions
methadone food
Applies to: methadone
GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of methadone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In 8 study subjects stabilized on methadone maintenance treatment, ingestion of regular strength grapefruit juice (200 mL one-half hour before and 200 mL simultaneously with the daily methadone dose) for five days resulted in an approximately 17% mean increase in methadone peak plasma concentration (Cmax) and systemic exposure (AUC) and a 14% mean decrease in apparent clearance for both the R(+) and S(-) enantiomers. Grapefruit juice did not affect the time to peak level (Tmax), terminal half-life, or apparent volume of distribution of methadone. No signs or symptoms of methadone toxicity or changes in intensity of withdrawal symptoms were reported in the study.
MANAGEMENT: Given the interindividual variability in the pharmacokinetics of methadone, a more significant interaction with grapefruit juice in certain patients cannot be ruled out. Patients treated with methadone should preferably avoid or limit the consumption of grapefruit juice, particularly during the induction of maintenance treatment.
References
- Iribarne C, Berthou F, Baird S, Dreano Y, Picart D, Bail JP, Beaune P, Menez JF (1996) "Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes." Chem Res Toxicol, 9, p. 365-73
- Oda Y, Kharasch ED (2001) "Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation." J Pharmacol Exp Ther, 298, p. 1021-32
- Benmebarek M, Devaud C, Gex-Fabry M, et al. (2004) "Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone." Clin Pharmacol Ther, 76, p. 55-63
- Foster DJ, Somogyi AA, Bochner F (1999) "Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4." Br J Clin Pharmacol, 47, p. 403-12
dextromethorphan food
Applies to: Phanatuss (dextromethorphan / guaifenesin)
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
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- 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.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
methadone food
Applies to: methadone
GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. 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.
MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.
References
- Linnoila M, Hakkinen S (1974) "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther, 15, p. 368-73
- Sturner WQ, Garriott JC (1973) "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA, 223, p. 1125-30
- Girre C, Hirschhorn M, Bertaux L, et al. (1991) "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol, 41, p. 147-52
- Levine B, Saady J, Fierro M, Valentour J (1984) "A hydromorphone and ethanol fatality." J Forensic Sci, 29, p. 655-9
- Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL (1985) "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol, 19, p. 398-401
- Carson DJ (1977) "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet, 1, p. 894-7
- Rosser WW (1980) "The interaction of propoxyphene with other drugs." Can Med Assoc J, 122, p. 149-50
- Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM (1982) "Distalgesic and ethanol-impaired function." Lancet, 2, p. 384
- Kiplinger GF, Sokol G, Rodda BE (1974) "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther, 212, p. 175-80
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.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
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