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Drug Interaction Report

23 potential interactions and/or warnings found for the following 6 drugs:

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Major

FLUoxetine venlafaxine

Applies to: Prozac (fluoxetine), Effexor XR (venlafaxine)

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

  1. Hansen TE, Dieter K, Keepers GA. Interaction of fluoxetine and pentazocine. Am J Psychiatry. 1990;147:949-50.
  2. Achamallah NS. Visual hallucinations after combining fluoxetine and dextromethorphan . Am J Psychiatry. 1992;149:1406.
  3. Nierenberg DW, Semprebon M. The central nervous system serotonin syndrome. Clin Pharmacol Ther. 1993;53:84-8.
  4. Metz A. Interaction between fluoxetine and buspirone. Can J Psychiatry. 1990;35:722-3.
  5. Goldberg RJ, Huk M. Serotonin syndrome from trazodone and buspirone. Psychosomatics. 1992;33:235-6.
  6. Product Information. D.H.E. 45 (dihydroergotamine). Sandoz Pharmaceuticals Corporation. 2002;PROD.
  7. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991;148:705-13.
  8. Ciraulo DA, Shader RI. Fluoxetine drug-drug interactions. II. J Clin Psychopharmacol. 1990;10:213-7.
  9. Ciraulo DA, Shader RI. Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics. J Clin Psychopharmacol. 1990;10:48-50.
  10. Product Information. Zoloft (sertraline). Roerig Division. 2001;PROD.
  11. Product Information. Prozac (fluoxetine). Dista Products Company. 2001;PROD.
  12. Noble WH, Baker A. MAO inhibitors and coronary artery surgery: a patient death. Can J Anaesth. 1992;39:1061-6.
  13. Insel TR, Roy BF, Cohen RM, Murphy DL. Possible development of the serotonin syndrome in man. Am J Psychiatry. 1982;139:954-5.
  14. Product Information. Effexor (venlafaxine). Wyeth-Ayerst Laboratories. 2001;PROD.
  15. 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.
  16. Product Information. Paxil (paroxetine). GlaxoSmithKline. 2001;PROD.
  17. Product Information. Flexeril (cyclobenzaprine). Merck & Co., Inc. 2001;PROD.
  18. Insler SR, Kraenzler EJ, Licina MG, Savage RM, Starr NJ. Cardiac surgery in a patient taking monoamine oxidase inhibitors - an adverse fentanyl reaction. Anesth Analg. 1994;78:593-7.
  19. Product Information. Imitrex (sumatriptan). Glaxo Wellcome. 2001;PROD.
  20. Ruiz F. Fluoxetine and the serotonin syndrome. Ann Emerg Med. 1994;24:983-5.
  21. Product Information. Luvox (fluvoxamine). Solvay Pharmaceuticals Inc. 2001;PROD.
  22. Reeves RR, Bullen JA. Serotonin syndrome produced by paroxetine and low-dose trazodone. Psychosomatics. 1995;36:159-60.
  23. Harvey AT, Preskorn SH. Interactions of serotonin reuptake inhibitors with tricyclic antidepressants. Arch Gen Psychiatry. 1995;52:783-4.
  24. Baetz M, Malcolm D. Serotonin syndrome from fluvoxamine and buspirone. Can J Psychiatry. 1995;40:428-9.
  25. Fischer P. Serotonin syndrome in the elderly after antidepressive monotherapy. J Clin Psychopharmacol. 1995;15:440-2.
  26. Corkeron MA. Serotonin syndrome - a potentially fatal complication of antidepressant therapy. Med J Aust. 1995;163:481-2.
  27. George TP, Godleski LS. Possible serotonin syndrome with trazodone addition to fluoxetine. Biol Psychiatry. 1996;39:384-5.
  28. Skop BP, Finkelstein JA, Mareth TR, Magoon MR, Brown TM. The serotonin syndrome associated wtih paroxetine, an over-the-counter cold remedy, and vascular disease. Am J Emerg Med. 1994;12:642-4.
  29. Mason BJ, Blackburn KH. Possible serotonin syndrome associated with tramadol and sertraline coadministration. Ann Pharmacother. 1997;31:175-7.
  30. John L, Perreault MM, Tao T, Blew PG. Serotonin syndrome associated with nefazodone and paroxetine. Ann Emerg Med. 1997;29:287-9.
  31. Product Information. Zomig (zolmitriptan). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  32. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  33. Mills KC. Serotonin syndrome: A clinical update. Crit Care Clin. 1997;13:763.
  34. Bhatara VS, Magnus RD, Paul KL, Preskorn SH. Serotonin syndrome induced by venlafaxine and fluoxetine: a case study in polypharmacy and potential pharmacodynamic and pharmacokinetic mechanisms. Ann Pharmacother. 1998;32:432-6.
  35. Product Information. Maxalt (rizatriptan). Merck & Co., Inc. 2001;PROD.
  36. Product Information. Celexa (citalopram). Forest Pharmaceuticals. 2001;PROD.
  37. Gardner DM, Lynd LD. Sumatriptan contraindications and the serotonin syndrome. Ann Pharmacother. 1998;32:33-8.
  38. Mathew NT, Tietjen GE, Lucker C. Serotonin syndrome complicating migraine pharmacotherapy. Cephalalgia. 1996;16:323-7.
  39. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG. Serotonin syndrome resulting from drug interactions. Med J Aust. 1998;169:523-5.
  40. Egberts AC, ter Borg J, Brodie-Meijer CC. Serotonin syndrome attributed to tramadol addition to paroxetine therapy. Int Clin Psychopharmacol. 1997;12:181-2.
  41. Weiner AL. Meperidine as a potential cause of serotonin syndrome in the emergency department. Acad Emerg Med. 1999;6:156-8.
  42. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  43. Gordon JB. SSRI's and St. John's Wort: possible toxicity? Am Fam Physician. 1998;57:950,953.
  44. Lantz MS, Buchalter E, Giambanco V. St. John's wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatr Neurol. 1999;12:7-10.
  45. Fugh-Berman A. Herb-drug interactions. Lancet. 2000;355:134-8.
  46. Product Information. Zyvox (linezolid). Pharmacia and Upjohn. 2001;PROD.
  47. Perry NK. Venlafaxine-induced serotonin syndrome with relapse following amitriptyline. Postgrad Med J. 2000;76:254-6.
  48. Manos GH. Possible serotonin syndrome associated with buspirone added to fluoxetine. Ann Pharmacother. 2000;34:871-4.
  49. Nijhawan PK, Katz G, Winter S. Psychiatric illness and the serotonin syndrome: an emerging adverse drug effect leading to intensive care unit admission. Crit Care Med. 1996;24:1086-9.
  50. Laird LK. Issues in the monopharmacotherapy and polypharmacotherapy of obsessive-compulsive disorder. Psychopharmacol Bull. 1996;32:569-78.
  51. Margolese HC, Chouinard G. Serotonin syndrome from addition of low-dose trazodone to nefazodone. Am J Psychiatry. 2000;157:1022.
  52. Mackay FJ, Dunn NR, Mann RD. Antidepressants and the serotonin syndrome in general practice. Br J Gen Pract. 1999;49:871-4.
  53. Smith DL, Wenegrat BG. A case report of serotonin syndrome associated with combined nefazodone and fluoxetine. J Clin Psychiatry. 2000;61:146.
  54. Rosebraugh CJ, floxkhart DA, Yasuda SU, Woosley RL. Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient. J Clin Pharmacol. 2001;41:224-7.
  55. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs. 2001;61:2163-75.
  56. Duggal HS, Fetchko J. Serotonin syndrome and atypical antipsychotics. Am J Psychiatry. 2002;159:672-3.
  57. Wigen CL, Goetz MB. Serotonin syndrome and linezolid. Clin Infect Dis. 2002;34:1651-2.
  58. Hammerness P, Parada H, Abrams A. Linezolid: MAOI Activity and Potential Drug Interactions. Psychosomatics. 2002;43:248-9.
  59. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  60. Dougherty JA, Young H, Shafi T. Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine. Ann Pharmacother. 2002;36:1647-1648.
  61. Turkel SB, Nadala JG, Wincor MZ. Possible serotonin syndrome in association with 5-HT3 antagonist agents. Psychosomatics. 2001;42:258-60.
  62. Martin TG. Serotonin syndrome. Ann Emerg Med. 1996;28:520-6.
  63. Lavery S, Ravi H, McDaniel WW, Pushkin YR. Linezolid and serotonin syndrome. Psychosomatics. 2001;42:432-4.
  64. Lane R, Baldwin D. Selective serotonin reuptake inhibitor--induced serotonin syndrome: review. J Clin Psychopharmacol. 1997;17:208-21.
  65. Bernard L, Stern R, Lew D, Hoffmeyer P. Serotonin syndrome after concomitant treatment with linezolid and citalopram. Clin Infect Dis. 2003;36:1197.
  66. Dannawi M. Possible serotonin syndrome after combination of buspirone and St John's Wort. J Psychopharmacol. 2002;16:401.
  67. Tissot TA. Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use. Anesthesiology. 2003;98:1511-1512.
  68. Hachem RY, Hicks K, Huen A, Raad I. Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients. Clin Infect Dis. 2003;37:E8-E11.
  69. Gillman PK. Linezolid and serotonin toxicity. Clin Infect Dis. 2003;37:1274-5.
  70. Roy S, Fortier LP. Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafexine. Can J Anaesth. 2003;50:32-5.
  71. Giese SY, Neborsky R. Serotonin syndrome: potential consequences of Meridia combined with Demerol or fentanyl. Plast Reconstr Surg. 2001;107:293-4.
  72. Jones SL, Athan E, O'Brien D. Serotonin syndrome due to co-administration of linezolid and venlafaxine. J Antimicrob Chemother. 2004;54:289-90.
  73. Tahir N. Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram. J Am Med Dir Assoc. 2004;5:111-3.
  74. Product Information. Cymbalta (duloxetine). Lilly, Eli and Company. 2004.
  75. Thomas CR, Rosenberg M, Blythe V, Meyer WJ 3rd. Serotonin syndrome and linezolid. J Am Acad Child Adolesc Psychiatry. 2004;43:790.
  76. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:1112-20.
  77. Bergeron L, Boule M, Perreault S. Serotonin toxicity associated with concomitant use of linezolid. Ann Pharmacother. 2005;39:956-61.
  78. Morales N, Vermette H. Serotonin syndrome associated with linezolid treatment after discontinuation of fluoxetine. Psychosomatics. 2005;46:274-5.
  79. Morales-Molina JA, Mateu-de Antonio J, Marin-Casino M, Grau S. Linezolid-associated serotonin syndrome: what we can learn from cases reported so far. J Antimicrob Chemother. 2005;56:1176-8.
  80. DeBellis RJ, Schaefer OP, Liquori M, Volturo GA. Linezolid-associated serotonin syndrome after concomitant treatment with citalopram and mirtazepine in a critically ill bone marrow transplant recipient. J Intensive Care Med. 2005;20:351-3.
  81. Hunter B, Kleinert MM, Osatnik J, Soria E. Serotonergic syndrome and abnormal ocular movements: worsening of rigidity by remifentanil? Anesth Analg. 2006;102:1589.
  82. Taylor JJ, Wilson JW, Estes LL. Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis. 2006;43:180-7.
  83. Strouse TB, Kerrihard TN, Forscher CA, Zakowski P. Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine. J Clin Psychopharmacol. 2006;26:681-683.
  84. Keegan MT, Brown DR, Rabinstein AA. Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs. Anesth Analg. 2006;103:1466-8.
  85. Paruchuri P, Godkar D, Anandacoomarswamy D, Sheth K, Niranjan S. Rare case of serotonin syndrome with therapeutic doses of paroxetine. Am J Ther. 2006;13:550-552.
  86. Steinberg M, Morin AK. Mild serotonin syndrome associated with concurrent linezolid and fluoxetine. Am J Health Syst Pharm. 2007;64:59-62.
  87. Packer S, Berman SA. Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid. Am J Psychiatry. 2007;164:346-7.
  88. Shapiro RE, Tepper SJ. The serotonin syndrome, triptans, and the potential for drug-drug interactions. Headache. 2007;47:266-9.
  89. Ailawadhi S, Sung KW, Carlson LA, Baer MR. Serotonin syndrome caused by interaction between citalopram and fentanyl. J Clin Pharm Ther. 2007;32:199-202.
  90. Product Information. Pristiq (desvenlafaxine). Wyeth Laboratories. 2008.
  91. Rang ST, Field J, Irving C. Serotonin toxicity caused by an interaction between fentanyl and paroxetine. Can J Anaesth. 2008;55:521-5.
  92. Product Information. Savella (milnacipran). Forest Pharmaceuticals. 2009.
  93. Product Information. Nucynta (tapentadol). PriCara Pharmaceuticals. 2009.
  94. Lee J, Franz L, Goforth HW. Serotonin syndrome in a chronic-pain patient receiving concurrent methadone, ciprofloxacin, and venlafaxine. Psychosomatics. 2009;50:638-9.
  95. Product Information. Viibryd (vilazodone). Trovis Pharmaceuticals LLC. 2011.
  96. Mugele J, Nanagas KA, Tormoehlen LM. Serotonin Syndrome Associated With MDPV Use: A Case Report. Ann Emerg Med. 2012.
  97. Product Information. Oleptro (trazodone). Labopharm Inc. 2012.
  98. Product Information. Fetzima (levomilnacipran). Forest Pharmaceuticals. 2013.
  99. Product Information. Brintellix (vortioxetine). Takeda Pharmaceuticals America. 2013.
  100. Product Information. Exxua (gepirone). Mission Pharmacal Company. 2023;1.
View all 100 references

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Moderate

FLUoxetine risperiDONE

Applies to: Prozac (fluoxetine), Risperdal (risperidone)

MONITOR: Coadministration with fluoxetine may increase the plasma concentrations of certain neuroleptic agents and potentiate the risk of extrapyramidal adverse effects. The proposed mechanism is inhibition of CYP450 2D6 metabolism by fluoxetine and its active metabolite, norfluoxetine. In 10 psychiatric patients stabilized on risperidone therapy (4 to 6 mg/day), the addition of fluoxetine (20 mg/day) led to a mean 4-fold increase in plasma risperidone concentrations and a 75% increase in levels of active moiety (i.e. sum of the concentrations of risperidone and its active 9-hydroxy metabolite). One patient developed severe akathisia and two developed Parkinsonian symptoms within the first two weeks. In contrast, mean plasma concentrations of haloperidol were elevated by just 20% following the addition of fluoxetine (20 mg/day for 7 to 10 days) in eight psychotic patients stabilized on haloperidol, and extrapyramidal side effects did not increase appreciably. However, haloperidol has been implicated clinically in various case reports, as has the phenothiazine fluphenazine. Some believe that a pharmacodynamic interaction may be partially responsible, as fluoxetine alone has been associated with extrapyramidal symptoms, possibly due to serotonergic inhibition of nigrostriatal dopaminergic pathways.

MANAGEMENT: Caution is recommended if fluoxetine is prescribed with phenothiazines or other neuroleptic agents that are thought to be metabolized by CYP450 2D6. Plasma neuroleptic levels and pharmacologic effects should be closely monitored and the dosage(s) adjusted accordingly, particularly following initiation or discontinuation of fluoxetine in patients who are stabilized on their neuroleptic regimen. Patients should be advised to contact their physician if they develop extrapyramidal symptoms such as tremor, shuffling gait, drooling, a mask-like face, tongue stiffness, muscle spasms or rigidity, and involuntary movements. Due to the long half-life of fluoxetine and norfluoxetine, the risk of an interaction may exist for an extended period (up to several weeks) after discontinuation of fluoxetine.

References

  1. Stein MH. Tardive dyskinesia in a patient taking haloperidol and fluoxetine. Am J Psychiatry. 1991;148:683.
  2. Tate JL. Extrapyramidal symptoms in a patient taking haloperidol and fluoxetine. Am J Psychiatry. 1989;146:399-400.
  3. Goff DC, Midha KK, Brotman AW, Waites M, Baldessarini RJ. Elevation of plasma concentrations of haloperidol after the addition of fluoxetine. Am J Psychiatry. 1991;148:790-2.
  4. Fluoxetine and extrapyramidal side effects. Am J Psychiatry. 1989;146:1352-3.
  5. Ketai R. Interaction between fluoxetine and neuroleptics. Am J Psychiatry. 1993;150:836-7.
  6. Baldessarini RJ, Marsh E. Fluoxetine and side effects. Arch Gen Psychiatry. 1990;47:191-2.
  7. Ciraulo DA, Shader RI. Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics. J Clin Psychopharmacol. 1990;10:48-50.
  8. Lock JD, Gwirtsman HE, Targ EF. Possible adverse drug interactions between fluoxetine and other psychotropics. J Clin Psychopharmacol. 1990;10:383-4.
  9. Dsouza DC, Bennett A, Abidargham A, Krystal JH. Precipitation of a psychoneuromotor syndrome by fluoxetine in a haloperidol-treated schizophrenic patient. J Clin Psychopharmacol. 1994;14:361-3.
  10. Avenoso A, Spina E, Campo G, Facciola G, Ferlito M, Zuccaro P, Perucca E, Caputi AP. Interaction between fluoxetine and haloperidol: Pharmacokinetic and clinical implications. Pharmacol Res. 1997;35:335-9.
  11. Tyndale RF, Kalow W, Inaba T. Oxidation of reduced haloperidol to haloperidol: involvement of human P450IID6 (sparteine/debrisoquine monooxygenase). Br J Clin Pharmacol. 1991;31:655-60.
  12. Bork JA, Rogers T, Wedlund PJ, deLeon J. A pilot study on risperidone metabolism: The role of cytochromes P450 2D6 and 3A. J Clin Psychiatry. 1999;60:469-76.
  13. Spina E, Avenoso A, Scordo MG, et al. Inhibition of Risperidone Metabolism by Fluoxetine in Patients With Schizophrenia: A Clinically Relevant Pharmacokinetic Drug Interaction. J Clin Psychopharmacol. 2002;22:419-423.
View all 13 references

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Moderate

risperiDONE venlafaxine

Applies to: Risperdal (risperidone), Effexor XR (venlafaxine)

MONITOR: Theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. The risk of an individual agent or a combination of these agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution and clinical monitoring are recommended if multiple agents associated with QT interval prolongation are prescribed together. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Glassman AH, Bigger JT Jr. Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death. Am J Psychiatry. 2001;158:1774-82.
  2. Witchel HJ, Hancox JC, Nutt DJ. Psychotropic drugs, cardiac arrhythmia, and sudden death. J Clin Psychopharmacol. 2003;23:58-77.
  3. Iannini PB. Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval. Expert Opin Drug Saf. 2002;1:121-8.
  4. Cerner Multum, Inc. UK Summary of Product Characteristics.
  5. Canadian Pharmacists Association. e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink 2006.
  6. Cerner Multum, Inc. Australian Product Information.
  7. EMA. European Medicines Agency. European Union. EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852 2013.
View all 7 references

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Moderate

ethinyl estradiol lamoTRIgine

Applies to: Norinyl 1+35 (ethinyl estradiol / norethindrone), Lamictal (lamotrigine)

MONITOR: Coadministration with estrogens or progestins may decrease the plasma concentrations and pharmacologic effects of lamotrigine due to induction of lamotrigine glucuronidation. One group of investigators cited seven suspected cases of this interaction in women treated with oral contraceptives that contained either ethinyl estradiol in combination with desogestrel or norethindrone or norethindrone alone. The contraceptives reduced plasma levels of lamotrigine by 41% to 64%, and a deterioration in seizure control was observed several days to two months after initiation of contraceptive use, necessitating an increase in lamotrigine dosage or discontinuation of the contraceptive. In some cases, contraceptive discontinuation led to lamotrigine toxicity that required dosage reduction. A pharmacokinetic study also reported similar reductions in lamotrigine plasma levels in patients on combination oral contraceptives, with lamotrigine clearance 2.5 times greater than in controls. The interaction is further supported by the fact that changes in hormone levels are known to influence the pharmacokinetics of glucuronidated drugs in humans, and elimination of lamotrigine is significantly increased during pregnancy. However, a population pharmacokinetics study in patients newly diagnosed with epilepsy and receiving oral lamotrigine monotherapy for up to 48 weeks found no significant effect of oral contraceptive use or dose on the oral clearance of lamotrigine. Lamotrigine also has been shown to have little or no effect on the pharmacokinetics of contraceptive hormones, although measurement of serum FSH, LH, and estradiol has indicated some loss of suppression of the hypothalamic-pituitary-ovarian axis. The clinical significance is unknown. Measurement of serum progesterone indicated no hormonal evidence of ovulation.

MANAGEMENT: Pharmacologic response and plasma lamotrigine levels should be monitored more closely whenever estrogen- and/or progestin-containing drugs are added to or withdrawn from therapy, and the lamotrigine dosage adjusted as necessary. The manufacturer's labeling should be consulted for detailed dosage recommendations. Patients should be advised to contact their physician if they experience loss of seizure control or symptoms of lamotrigine toxicity such as ataxia, nystagmus, increased seizures, irregular heartbeat, and changes in mental status. In patients receiving oral contraceptives, gradual transient increases in lamotrigine levels will occur during the pill-free week for women not also taking an enzyme-inducing drug (e.g., carbamazepine, phenytoin, phenobarbital, primidone, rifampin). The increase in lamotrigine levels will be greater if the dose of lamotrigine is increased in the few days before or during the pill-free week. Although diminished contraceptive efficacy has not been reported, the possibility should be considered. Patients should be instructed to promptly report changes in their menstrual pattern.

References

  1. Product Information. Lamictal (lamotrigine). Glaxo Wellcome. 2001;PROD.
  2. Tomson T, Ohman I, Vitols S. Lamotrigine in pregnancy and lactation: A case report. Epilepsia. 1997;38:1039-41.
  3. Wilbur K, Ensom MHH. Pharmacokinetic drug interactions between oral contraceptives and second-generation anticonvulsants. Clin Pharmacokinet. 2000;38:355-65.
  4. Sabers A, Buchholt JM, Uldall P, Hansen EL. Lamotrigine plasma levels reduced by oral contraceptives. Epilepsy Res. 2001;47:151-4.
  5. Miners JO, Mackenzie PI. Drug glucuronidation in humans. Pharmacol Ther. 1991;51:347-69.
  6. Ohman I, Vitols S, Tomson T. Lamotrigine in pregnancy: pharmacokinetics during delivery, in the neonate, and during lactation. Epilepsia. 2000;41:706-13.
  7. Holdich T, Whiteman P, Orme M, Back D, Ward S. Effect of lamotrigine on the pharmacology of the combined oral contraceptive pill. Epilepsia. 1991;32(Suppl):96.
  8. Hussein Z, Posner J. Population pharmacokinetics of lamotrigine monotherapy in patients with epilepsy: retrospective analysis of routine monitoring data. Br J Clin Pharmacol. 1997;43:457-65.
  9. Sabers A, Ohman I, Christensen J, Tomson T. Oral contraceptives reduce lamotrigine plasma levels. Neurology. 2003;61:570-1.
  10. O'Brien MD, Guillebaud J. Contraception for women with epilepsy. Epilepsia. 2006;47:1419-22.
  11. Product Information. Nextstellis (drospirenone-estetrol). Mayne Pharma. 2021.
View all 11 references

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Moderate

FLUoxetine lamoTRIgine

Applies to: Prozac (fluoxetine), Lamictal (lamotrigine)

MONITOR: The efficacy of anticonvulsants may be diminished during coadministration with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitor (SNRIs). Antidepressants including SSRIs and SNRIs can reduce seizure threshold. In clinical trials, convulsions have typically been reported in 0.1% to 0.3% of patients receiving SSRIs for major depressive disorders. There have been rare reports of prolonged seizures in patients on fluoxetine receiving electroconvulsive therapy (ECT).

MONITOR: Coadministration of SSRIs or SNRIs may potentiate the central nervous system (CNS) adverse effects of anticonvulsants such as somnolence and cognitive and psychomotor impairment.

MONITOR: Coadministration of SSRIs or SNRIs with some anticonvulsants, particularly carbamazepine, eslicarbazepine, oxcarbazepine and valproic acid, may increase the risk of hyponatremia. Treatment with SSRIs or SNRIs has been associated with hyponatremia, which may be due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in many cases. While generally reversible following discontinuation of SSRI/SNRI treatment, cases with serum sodium lower than 110 mmol/L have been reported. Hyponatremia and SIADH may also result from treatment with some anticonvulsants. The risk appears to be dose-related, and elderly patients and patients who are volume depleted (e.g., diuretic use) may be at greater risk.

MANAGEMENT: SSRIs and SNRIs should be avoided in patients with unstable epilepsy, and used cautiously in patients with epilepsy controlled with anticonvulsant medications. Treatment with SSRIs and SNRIs should be discontinued if seizures develop or seizure frequency increases. Patients receiving SSRIs or SNRIs with anticonvulsants, particularly carbamazepine, eslicarbazepine, oxcarbazepine and/or valproic acid, should also have serum sodium levels measured regularly and monitored for development of hyponatremia, particularly when higher dosages of these medications are used. Signs and symptoms of hyponatremia include nausea, vomiting, headache, difficulty concentrating, memory impairment, confusion, malaise, lethargy, muscle weakness or spasms, and unsteadiness. In more severe and/or acute cases, hallucination, syncope, seizure, coma, respiratory arrest, and death may occur. Discontinuation of SSRIs and SNRIs should be considered in patients who develop symptomatic hyponatremia, and appropriate medical intervention instituted. All patients receiving concomitant therapy with SSRIs or SNRIs and anticonvulsants should be counseled against driving, operating machinery, or engaging in potentially 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.

References

  1. Product Information. Tegretol (carbamazepine). Novartis Pharmaceuticals. 2002;PROD.
  2. Product Information. Zoloft (sertraline). Roerig Division. 2001;PROD.
  3. Product Information. Prozac (fluoxetine). Dista Products Company. 2001;PROD.
  4. Product Information. Effexor (venlafaxine). Wyeth-Ayerst Laboratories. 2001;PROD.
  5. Product Information. Paxil (paroxetine). GlaxoSmithKline. 2001;PROD.
  6. Product Information. Luvox (fluvoxamine). Solvay Pharmaceuticals Inc. 2001;PROD.
  7. Product Information. Celexa (citalopram). Forest Pharmaceuticals. 2001;PROD.
  8. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  9. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  10. Product Information. Cymbalta (duloxetine). Lilly, Eli and Company. 2004.
  11. Cerner Multum, Inc. UK Summary of Product Characteristics.
  12. Product Information. Pristiq (desvenlafaxine). Wyeth Laboratories. 2008.
  13. Product Information. Savella (milnacipran). Forest Pharmaceuticals. 2009.
  14. Product Information. Fetzima (levomilnacipran). Forest Pharmaceuticals. 2013.
  15. Product Information. Aptiom (eslicarbazepine). Sunovion Pharmaceuticals Inc. 2013.
  16. Belcastro V, Costa C, Striano P. Levetiracetam-associated hyponatremia. Seizure. 2008;17:389-90.
  17. Bavbek N, Alkan R, Uz E, Kaftan O, Akcay A. Hyponatremia associated with sodium valproate in a 22-year-old male. Nephrol Dial Transplant. 2008;23:epub.
  18. Patel KR, Meesala A, Stanilla JK. Sodium valproate-induced hyponatremia: a case report. Prim Care Companion J Clin Psychiatry. 2010;12:epub.
  19. Gandhi S, McArthur E, Mamdani MM, et al. Antiepileptic drugs and hyponatremia in older adults: Two population-based cohort studies. Epilepsia. 2016;57:2067-79.
  20. Falhammar H, Lindh JD, Calissendorff J, et al. Differences in associations of antiepileptic drugs and hospitalization due to hyponatremia: A population-based case-control study. Seizure. 2018;59:28-33.
View all 20 references

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Moderate

norethindrone lamoTRIgine

Applies to: Norinyl 1+35 (ethinyl estradiol / norethindrone), Lamictal (lamotrigine)

MONITOR: Coadministration with estrogens or progestins may decrease the plasma concentrations and pharmacologic effects of lamotrigine due to induction of lamotrigine glucuronidation. One group of investigators cited seven suspected cases of this interaction in women treated with oral contraceptives that contained either ethinyl estradiol in combination with desogestrel or norethindrone or norethindrone alone. The contraceptives reduced plasma levels of lamotrigine by 41% to 64%, and a deterioration in seizure control was observed several days to two months after initiation of contraceptive use, necessitating an increase in lamotrigine dosage or discontinuation of the contraceptive. In some cases, contraceptive discontinuation led to lamotrigine toxicity that required dosage reduction. A pharmacokinetic study also reported similar reductions in lamotrigine plasma levels in patients on combination oral contraceptives, with lamotrigine clearance 2.5 times greater than in controls. The interaction is further supported by the fact that changes in hormone levels are known to influence the pharmacokinetics of glucuronidated drugs in humans, and elimination of lamotrigine is significantly increased during pregnancy. However, a population pharmacokinetics study in patients newly diagnosed with epilepsy and receiving oral lamotrigine monotherapy for up to 48 weeks found no significant effect of oral contraceptive use or dose on the oral clearance of lamotrigine. Lamotrigine also has been shown to have little or no effect on the pharmacokinetics of contraceptive hormones, although measurement of serum FSH, LH, and estradiol has indicated some loss of suppression of the hypothalamic-pituitary-ovarian axis. The clinical significance is unknown. Measurement of serum progesterone indicated no hormonal evidence of ovulation.

MANAGEMENT: Pharmacologic response and plasma lamotrigine levels should be monitored more closely whenever estrogen- and/or progestin-containing drugs are added to or withdrawn from therapy, and the lamotrigine dosage adjusted as necessary. The manufacturer's labeling should be consulted for detailed dosage recommendations. Patients should be advised to contact their physician if they experience loss of seizure control or symptoms of lamotrigine toxicity such as ataxia, nystagmus, increased seizures, irregular heartbeat, and changes in mental status. In patients receiving oral contraceptives, gradual transient increases in lamotrigine levels will occur during the pill-free week for women not also taking an enzyme-inducing drug (e.g., carbamazepine, phenytoin, phenobarbital, primidone, rifampin). The increase in lamotrigine levels will be greater if the dose of lamotrigine is increased in the few days before or during the pill-free week. Although diminished contraceptive efficacy has not been reported, the possibility should be considered. Patients should be instructed to promptly report changes in their menstrual pattern.

References

  1. Product Information. Lamictal (lamotrigine). Glaxo Wellcome. 2001;PROD.
  2. Tomson T, Ohman I, Vitols S. Lamotrigine in pregnancy and lactation: A case report. Epilepsia. 1997;38:1039-41.
  3. Wilbur K, Ensom MHH. Pharmacokinetic drug interactions between oral contraceptives and second-generation anticonvulsants. Clin Pharmacokinet. 2000;38:355-65.
  4. Sabers A, Buchholt JM, Uldall P, Hansen EL. Lamotrigine plasma levels reduced by oral contraceptives. Epilepsy Res. 2001;47:151-4.
  5. Miners JO, Mackenzie PI. Drug glucuronidation in humans. Pharmacol Ther. 1991;51:347-69.
  6. Ohman I, Vitols S, Tomson T. Lamotrigine in pregnancy: pharmacokinetics during delivery, in the neonate, and during lactation. Epilepsia. 2000;41:706-13.
  7. Holdich T, Whiteman P, Orme M, Back D, Ward S. Effect of lamotrigine on the pharmacology of the combined oral contraceptive pill. Epilepsia. 1991;32(Suppl):96.
  8. Hussein Z, Posner J. Population pharmacokinetics of lamotrigine monotherapy in patients with epilepsy: retrospective analysis of routine monitoring data. Br J Clin Pharmacol. 1997;43:457-65.
  9. Sabers A, Ohman I, Christensen J, Tomson T. Oral contraceptives reduce lamotrigine plasma levels. Neurology. 2003;61:570-1.
  10. O'Brien MD, Guillebaud J. Contraception for women with epilepsy. Epilepsia. 2006;47:1419-22.
  11. Product Information. Nextstellis (drospirenone-estetrol). Mayne Pharma. 2021.
View all 11 references

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Moderate

risperiDONE lamoTRIgine

Applies to: Risperdal (risperidone), Lamictal (lamotrigine)

MONITOR: A case report suggests that lamotrigine may increase the plasma concentrations of risperidone. The mechanism of interaction is unknown. The case patient was a 26-year-old woman with schizophrenia who had been treated with clozapine 550 mg daily for 5 years and risperidone 8 mg daily for 4 weeks. Lamotrigine was added due to inadequate response. The patient's risperidone plasma level was 69 ng/mL while receiving lamotrigine 175 mg/day; 284 ng/mL when lamotrigine was increased to 200 mg/day; and 412 ng/mL at lamotrigine 225 mg/day. The patient complained of dizziness and tiredness. Risperidone dosage was reduced to 2 mg/day and discontinued a week later. Pharmacodynamically, additive central nervous system depression may also occur when these drugs are used in combination, resulting in impairment of judgment, thinking, and/or psychomotor skills.

MANAGEMENT: Until more data are available, caution is advised if risperidone must be used in combination with lamotrigine. Pharmacologic response and serum risperidone levels should be monitored more closely whenever lamotrigine is added to or withdrawn from therapy, and the risperidone dosage adjusted as necessary. Patients should be advised to notify their physician if they experience potential signs and symptoms of risperidone toxicity such as excessive sedation, dizziness, tachycardia, seizures, and extrapyramidal symptoms. Ambulatory patients should also be counseled to avoid activities requiring mental alertness (e.g., driving or operating hazardous machinery) until they know how these agents affect them.

References

  1. Bienentreu SD, Kronmuller KT. Increase in risperidone plasma level with lamotrigine. Am J Psychiatry. 2005;162:811-2.

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Moderate

venlafaxine lamoTRIgine

Applies to: Effexor XR (venlafaxine), Lamictal (lamotrigine)

MONITOR: The efficacy of anticonvulsants may be diminished during coadministration with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitor (SNRIs). Antidepressants including SSRIs and SNRIs can reduce seizure threshold. In clinical trials, convulsions have typically been reported in 0.1% to 0.3% of patients receiving SSRIs for major depressive disorders. There have been rare reports of prolonged seizures in patients on fluoxetine receiving electroconvulsive therapy (ECT).

MONITOR: Coadministration of SSRIs or SNRIs may potentiate the central nervous system (CNS) adverse effects of anticonvulsants such as somnolence and cognitive and psychomotor impairment.

MONITOR: Coadministration of SSRIs or SNRIs with some anticonvulsants, particularly carbamazepine, eslicarbazepine, oxcarbazepine and valproic acid, may increase the risk of hyponatremia. Treatment with SSRIs or SNRIs has been associated with hyponatremia, which may be due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in many cases. While generally reversible following discontinuation of SSRI/SNRI treatment, cases with serum sodium lower than 110 mmol/L have been reported. Hyponatremia and SIADH may also result from treatment with some anticonvulsants. The risk appears to be dose-related, and elderly patients and patients who are volume depleted (e.g., diuretic use) may be at greater risk.

MANAGEMENT: SSRIs and SNRIs should be avoided in patients with unstable epilepsy, and used cautiously in patients with epilepsy controlled with anticonvulsant medications. Treatment with SSRIs and SNRIs should be discontinued if seizures develop or seizure frequency increases. Patients receiving SSRIs or SNRIs with anticonvulsants, particularly carbamazepine, eslicarbazepine, oxcarbazepine and/or valproic acid, should also have serum sodium levels measured regularly and monitored for development of hyponatremia, particularly when higher dosages of these medications are used. Signs and symptoms of hyponatremia include nausea, vomiting, headache, difficulty concentrating, memory impairment, confusion, malaise, lethargy, muscle weakness or spasms, and unsteadiness. In more severe and/or acute cases, hallucination, syncope, seizure, coma, respiratory arrest, and death may occur. Discontinuation of SSRIs and SNRIs should be considered in patients who develop symptomatic hyponatremia, and appropriate medical intervention instituted. All patients receiving concomitant therapy with SSRIs or SNRIs and anticonvulsants should be counseled against driving, operating machinery, or engaging in potentially 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.

References

  1. Product Information. Tegretol (carbamazepine). Novartis Pharmaceuticals. 2002;PROD.
  2. Product Information. Zoloft (sertraline). Roerig Division. 2001;PROD.
  3. Product Information. Prozac (fluoxetine). Dista Products Company. 2001;PROD.
  4. Product Information. Effexor (venlafaxine). Wyeth-Ayerst Laboratories. 2001;PROD.
  5. Product Information. Paxil (paroxetine). GlaxoSmithKline. 2001;PROD.
  6. Product Information. Luvox (fluvoxamine). Solvay Pharmaceuticals Inc. 2001;PROD.
  7. Product Information. Celexa (citalopram). Forest Pharmaceuticals. 2001;PROD.
  8. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  9. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  10. Product Information. Cymbalta (duloxetine). Lilly, Eli and Company. 2004.
  11. Cerner Multum, Inc. UK Summary of Product Characteristics.
  12. Product Information. Pristiq (desvenlafaxine). Wyeth Laboratories. 2008.
  13. Product Information. Savella (milnacipran). Forest Pharmaceuticals. 2009.
  14. Product Information. Fetzima (levomilnacipran). Forest Pharmaceuticals. 2013.
  15. Product Information. Aptiom (eslicarbazepine). Sunovion Pharmaceuticals Inc. 2013.
  16. Belcastro V, Costa C, Striano P. Levetiracetam-associated hyponatremia. Seizure. 2008;17:389-90.
  17. Bavbek N, Alkan R, Uz E, Kaftan O, Akcay A. Hyponatremia associated with sodium valproate in a 22-year-old male. Nephrol Dial Transplant. 2008;23:epub.
  18. Patel KR, Meesala A, Stanilla JK. Sodium valproate-induced hyponatremia: a case report. Prim Care Companion J Clin Psychiatry. 2010;12:epub.
  19. Gandhi S, McArthur E, Mamdani MM, et al. Antiepileptic drugs and hyponatremia in older adults: Two population-based cohort studies. Epilepsia. 2016;57:2067-79.
  20. Falhammar H, Lindh JD, Calissendorff J, et al. Differences in associations of antiepileptic drugs and hospitalization due to hyponatremia: A population-based case-control study. Seizure. 2018;59:28-33.
View all 20 references

Switch to consumer interaction data

Moderate

FLUoxetine cannabis (Schedule I substance)

Applies to: Prozac (fluoxetine), cannabis

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory 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.

References

  1. Hamilton MJ, Bush M, Smith P, Peck AW. The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Br J Clin Pharmacol. 1982;14:791-7.
  2. Stambaugh JE, Lane C. Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination. Cancer Invest. 1983;1:111-7.
  3. Sotaniemi EA, Anttila M, Rautio A, et al. Propranolol and sotalol metabolism after a drinking party. Clin Pharmacol Ther. 1981;29:705-10.
  4. Grabowski BS, Cady WJ, Young WW, Emery JF. Effects of acute alcohol administration on propranolol absorption. Int J Clin Pharmacol Ther Toxicol. 1980;18:317-9.
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther. 1988;43:412-9.
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM. Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol. 1977;11:345-9.
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  8. Naylor GJ, McHarg A. Profound hypothermia on combined lithium carbonate and diazepam treatment. Br Med J. 1977;2:22.
  9. Stovner J, Endresen R. Intravenous anaesthesia with diazepam. Acta Anaesthesiol Scand. 1965;24:223-7.
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF. Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation. J Pharm Pharmacol. 1984;36:244-7.
  11. Feldman SA, Crawley BE. Interaction of diazepam with the muscle-relaxant drugs. Br Med J. 1970;1:336-8.
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam and alprazolam. Clin Pharmacol Ther. 1984;36:451-5.
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology (Berl). 1988;96:63-6.
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I. Midazolam-morphine sedative interaction in patients. Anesth Analg. 1989;68:282-5.
  15. Product Information. Iopidine (apraclonidine ophthalmic). Alcon Laboratories Inc. PROD.
  16. Greiff JMC, Rowbotham D. Pharmacokinetic drug interactions with gastrointestinal motility modifying agents. Clin Pharmacokinet. 1994;27:447-61.
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G. The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine. Acta Psychiatr Scand. 1989;80 Suppl:95-8.
  18. Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother. 1995;29:603-9.
  19. Product Information. Ultram (tramadol). McNeil Pharmaceutical. 2001;PROD.
  20. Product Information. Artane (trihexyphenidyl). Lederle Laboratories. 2001;PROD.
  21. Product Information. Ultiva (remifentanil). Mylan Institutional (formally Bioniche Pharma USA Inc). 2001;PROD.
  22. Product Information. Seroquel (quetiapine). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  23. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  24. Product Information. Tasmar (tolcapone). Valeant Pharmaceuticals. 2001;PROD.
  25. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  26. Product Information. Precedex (dexmedetomidine). Abbott Pharmaceutical. 2001;PROD.
  27. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  28. Ferslew KE, Hagardorn AN, McCormick WF. A fatal interaction of methocarbamol and ethanol in an accidental poisoning. J Forensic Sci. 1990;35:477-82.
  29. Plushner SL. Valerian: valeriana officinalis. Am J Health Syst Pharm. 2000;57:328-35.
  30. Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc. 2002.
  31. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  32. Cerner Multum, Inc. UK Summary of Product Characteristics.
  33. Cerner Multum, Inc. Australian Product Information.
  34. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  35. Product Information. Belsomra (suvorexant). Merck & Co., Inc. 2014.
  36. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 36 references

Switch to consumer interaction data

Moderate

risperiDONE cannabis (Schedule I substance)

Applies to: Risperdal (risperidone), cannabis

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory 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.

References

  1. Hamilton MJ, Bush M, Smith P, Peck AW. The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Br J Clin Pharmacol. 1982;14:791-7.
  2. Stambaugh JE, Lane C. Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination. Cancer Invest. 1983;1:111-7.
  3. Sotaniemi EA, Anttila M, Rautio A, et al. Propranolol and sotalol metabolism after a drinking party. Clin Pharmacol Ther. 1981;29:705-10.
  4. Grabowski BS, Cady WJ, Young WW, Emery JF. Effects of acute alcohol administration on propranolol absorption. Int J Clin Pharmacol Ther Toxicol. 1980;18:317-9.
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther. 1988;43:412-9.
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM. Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol. 1977;11:345-9.
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  8. Naylor GJ, McHarg A. Profound hypothermia on combined lithium carbonate and diazepam treatment. Br Med J. 1977;2:22.
  9. Stovner J, Endresen R. Intravenous anaesthesia with diazepam. Acta Anaesthesiol Scand. 1965;24:223-7.
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF. Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation. J Pharm Pharmacol. 1984;36:244-7.
  11. Feldman SA, Crawley BE. Interaction of diazepam with the muscle-relaxant drugs. Br Med J. 1970;1:336-8.
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam and alprazolam. Clin Pharmacol Ther. 1984;36:451-5.
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology (Berl). 1988;96:63-6.
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I. Midazolam-morphine sedative interaction in patients. Anesth Analg. 1989;68:282-5.
  15. Product Information. Iopidine (apraclonidine ophthalmic). Alcon Laboratories Inc. PROD.
  16. Greiff JMC, Rowbotham D. Pharmacokinetic drug interactions with gastrointestinal motility modifying agents. Clin Pharmacokinet. 1994;27:447-61.
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G. The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine. Acta Psychiatr Scand. 1989;80 Suppl:95-8.
  18. Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother. 1995;29:603-9.
  19. Product Information. Ultram (tramadol). McNeil Pharmaceutical. 2001;PROD.
  20. Product Information. Artane (trihexyphenidyl). Lederle Laboratories. 2001;PROD.
  21. Product Information. Ultiva (remifentanil). Mylan Institutional (formally Bioniche Pharma USA Inc). 2001;PROD.
  22. Product Information. Seroquel (quetiapine). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  23. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  24. Product Information. Tasmar (tolcapone). Valeant Pharmaceuticals. 2001;PROD.
  25. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  26. Product Information. Precedex (dexmedetomidine). Abbott Pharmaceutical. 2001;PROD.
  27. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  28. Ferslew KE, Hagardorn AN, McCormick WF. A fatal interaction of methocarbamol and ethanol in an accidental poisoning. J Forensic Sci. 1990;35:477-82.
  29. Plushner SL. Valerian: valeriana officinalis. Am J Health Syst Pharm. 2000;57:328-35.
  30. Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc. 2002.
  31. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  32. Cerner Multum, Inc. UK Summary of Product Characteristics.
  33. Cerner Multum, Inc. Australian Product Information.
  34. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  35. Product Information. Belsomra (suvorexant). Merck & Co., Inc. 2014.
  36. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 36 references

Switch to consumer interaction data

Moderate

venlafaxine cannabis (Schedule I substance)

Applies to: Effexor XR (venlafaxine), cannabis

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory 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.

References

  1. Hamilton MJ, Bush M, Smith P, Peck AW. The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Br J Clin Pharmacol. 1982;14:791-7.
  2. Stambaugh JE, Lane C. Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination. Cancer Invest. 1983;1:111-7.
  3. Sotaniemi EA, Anttila M, Rautio A, et al. Propranolol and sotalol metabolism after a drinking party. Clin Pharmacol Ther. 1981;29:705-10.
  4. Grabowski BS, Cady WJ, Young WW, Emery JF. Effects of acute alcohol administration on propranolol absorption. Int J Clin Pharmacol Ther Toxicol. 1980;18:317-9.
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther. 1988;43:412-9.
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM. Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol. 1977;11:345-9.
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  8. Naylor GJ, McHarg A. Profound hypothermia on combined lithium carbonate and diazepam treatment. Br Med J. 1977;2:22.
  9. Stovner J, Endresen R. Intravenous anaesthesia with diazepam. Acta Anaesthesiol Scand. 1965;24:223-7.
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF. Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation. J Pharm Pharmacol. 1984;36:244-7.
  11. Feldman SA, Crawley BE. Interaction of diazepam with the muscle-relaxant drugs. Br Med J. 1970;1:336-8.
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam and alprazolam. Clin Pharmacol Ther. 1984;36:451-5.
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology (Berl). 1988;96:63-6.
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I. Midazolam-morphine sedative interaction in patients. Anesth Analg. 1989;68:282-5.
  15. Product Information. Iopidine (apraclonidine ophthalmic). Alcon Laboratories Inc. PROD.
  16. Greiff JMC, Rowbotham D. Pharmacokinetic drug interactions with gastrointestinal motility modifying agents. Clin Pharmacokinet. 1994;27:447-61.
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G. The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine. Acta Psychiatr Scand. 1989;80 Suppl:95-8.
  18. Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother. 1995;29:603-9.
  19. Product Information. Ultram (tramadol). McNeil Pharmaceutical. 2001;PROD.
  20. Product Information. Artane (trihexyphenidyl). Lederle Laboratories. 2001;PROD.
  21. Product Information. Ultiva (remifentanil). Mylan Institutional (formally Bioniche Pharma USA Inc). 2001;PROD.
  22. Product Information. Seroquel (quetiapine). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  23. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  24. Product Information. Tasmar (tolcapone). Valeant Pharmaceuticals. 2001;PROD.
  25. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  26. Product Information. Precedex (dexmedetomidine). Abbott Pharmaceutical. 2001;PROD.
  27. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  28. Ferslew KE, Hagardorn AN, McCormick WF. A fatal interaction of methocarbamol and ethanol in an accidental poisoning. J Forensic Sci. 1990;35:477-82.
  29. Plushner SL. Valerian: valeriana officinalis. Am J Health Syst Pharm. 2000;57:328-35.
  30. Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc. 2002.
  31. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  32. Cerner Multum, Inc. UK Summary of Product Characteristics.
  33. Cerner Multum, Inc. Australian Product Information.
  34. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  35. Product Information. Belsomra (suvorexant). Merck & Co., Inc. 2014.
  36. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 36 references

Switch to consumer interaction data

Moderate

lamoTRIgine cannabis (Schedule I substance)

Applies to: Lamictal (lamotrigine), cannabis

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory 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.

References

  1. Hamilton MJ, Bush M, Smith P, Peck AW. The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Br J Clin Pharmacol. 1982;14:791-7.
  2. Stambaugh JE, Lane C. Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination. Cancer Invest. 1983;1:111-7.
  3. Sotaniemi EA, Anttila M, Rautio A, et al. Propranolol and sotalol metabolism after a drinking party. Clin Pharmacol Ther. 1981;29:705-10.
  4. Grabowski BS, Cady WJ, Young WW, Emery JF. Effects of acute alcohol administration on propranolol absorption. Int J Clin Pharmacol Ther Toxicol. 1980;18:317-9.
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther. 1988;43:412-9.
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM. Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol. 1977;11:345-9.
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  8. Naylor GJ, McHarg A. Profound hypothermia on combined lithium carbonate and diazepam treatment. Br Med J. 1977;2:22.
  9. Stovner J, Endresen R. Intravenous anaesthesia with diazepam. Acta Anaesthesiol Scand. 1965;24:223-7.
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF. Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation. J Pharm Pharmacol. 1984;36:244-7.
  11. Feldman SA, Crawley BE. Interaction of diazepam with the muscle-relaxant drugs. Br Med J. 1970;1:336-8.
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam and alprazolam. Clin Pharmacol Ther. 1984;36:451-5.
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology (Berl). 1988;96:63-6.
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I. Midazolam-morphine sedative interaction in patients. Anesth Analg. 1989;68:282-5.
  15. Product Information. Iopidine (apraclonidine ophthalmic). Alcon Laboratories Inc. PROD.
  16. Greiff JMC, Rowbotham D. Pharmacokinetic drug interactions with gastrointestinal motility modifying agents. Clin Pharmacokinet. 1994;27:447-61.
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G. The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine. Acta Psychiatr Scand. 1989;80 Suppl:95-8.
  18. Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother. 1995;29:603-9.
  19. Product Information. Ultram (tramadol). McNeil Pharmaceutical. 2001;PROD.
  20. Product Information. Artane (trihexyphenidyl). Lederle Laboratories. 2001;PROD.
  21. Product Information. Ultiva (remifentanil). Mylan Institutional (formally Bioniche Pharma USA Inc). 2001;PROD.
  22. Product Information. Seroquel (quetiapine). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  23. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  24. Product Information. Tasmar (tolcapone). Valeant Pharmaceuticals. 2001;PROD.
  25. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  26. Product Information. Precedex (dexmedetomidine). Abbott Pharmaceutical. 2001;PROD.
  27. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  28. Ferslew KE, Hagardorn AN, McCormick WF. A fatal interaction of methocarbamol and ethanol in an accidental poisoning. J Forensic Sci. 1990;35:477-82.
  29. Plushner SL. Valerian: valeriana officinalis. Am J Health Syst Pharm. 2000;57:328-35.
  30. Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc. 2002.
  31. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  32. Cerner Multum, Inc. UK Summary of Product Characteristics.
  33. Cerner Multum, Inc. Australian Product Information.
  34. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  35. Product Information. Belsomra (suvorexant). Merck & Co., Inc. 2014.
  36. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 36 references

Switch to consumer interaction data

No other interactions were found between your selected drugs. However, this does not necessarily mean no other interactions exist. Always consult your healthcare provider.

Drug and food interactions

Moderate

FLUoxetine food

Applies to: Prozac (fluoxetine)

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. 1986;15:31-7.
  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

Switch to consumer interaction data

Moderate

norethindrone food

Applies to: Norinyl 1+35 (ethinyl estradiol / norethindrone)

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

  1. Edgar B, Bailey D, Bergstrand R, et al. Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance. Eur J Clin Pharmacol. 1992;42:313-7.
  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW. The influence of caffeine on the steady-state pharmacokinetics of theophylline. Clin Pharmacol Ther. 1991;49:248-55.
  3. Bailey DG, Arnold JM, Munoz C, Spence JD. Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin. Clin Pharmacol Ther. 1993;53:637-42.
  4. Bailey DG, Arnold JMO, Spence JD. Grapefruit juice and drugs - how significant is the interaction. Clin Pharmacokinet. 1994;26:91-8.
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A. Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation. Pharmazie. 1994;49:522-4.
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD. Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics. Clin Pharmacol Ther. 1993;54:589-94.
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG. Drug-food interactions in clinical practice. J Fam Pract. 1995;40:376-84.
  8. Grapefruit juice interactions with drugs. Med Lett Drugs Ther. 1995;37:73-4.
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ. Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice. Clin Pharmacol Ther. 1995;58:127-31.
  10. Min DI, Ku YM, Geraets DR, Lee HC. Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers. J Clin Pharmacol. 1996;36:469-76.
  11. Majeed A, Kareem A. Effect of grapefruit juice on cyclosporine pharmacokinetics. Pediatr Nephrol. 1996;10:395.
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS. Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice. Br J Clin Pharmacol. 1996;42:p662.
  13. Josefsson M, Zackrisson AL, Ahlner J. Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers. Eur J Clin Pharmacol. 1996;51:189-93.
  14. Kantola T, Kivisto KT, Neuvonen PJ. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther. 1998;63:397-402.
  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A. Interaction between grapefruit juice and diazepam in humans. Eur J Drug Metab Pharmacokinet. 1998;23:55-9.
  16. Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46:101-10.
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans. Clin Pharmacol Ther. 1998;64:248-56.
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK. Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy. Clin Pharmacol Ther. 1998;64:286-8.
  19. Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther. 1998;64:477-83.
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. Grapefruit juice increases oral nimodipine bioavailability. Int J Clin Pharmacol Ther. 1998;36:126-32.
  21. Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther. 1999;66:118-27.
  22. Eagling VA, Profit L, Back DJ. 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. 1999;48:543-52.
  23. Damkier P, Hansen LL, Brosen K. Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine. Br J Clin Pharmacol. 1999;48:829-38.
  24. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC. The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study. Clin Ther. 1999;21:1890-9.
  25. Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000;38:41-57.
  26. Gunston GD, Mehta U. Potentially serious drug interactions with grapefruit juice. S Afr Med J. 2000;90:41.
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model. Br J Clin Pharmacol. 2000;49:49-58.
  28. Libersa CC, Brique SA, Motte KB, et al. Dramatic inhibition of amiodarone metabolism induced by grapefruit juice. Br J Clin Pharmacol. 2000;49:373-8.
  29. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients. Clin Pharmacol Ther. 2000;68:468-77.
  30. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E. Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers. Ther Drug Monit. 2001;23:369-73.
  31. 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. 1993;44:295-8.
  32. Flanagan D. Understanding the grapefruit-drug interaction. Gen Dent. 2005;53:282-5; quiz 286.
View all 32 references

Switch to consumer interaction data

Moderate

risperiDONE food

Applies to: Risperdal (risperidone)

GENERALLY AVOID: Risperidone oral solution is not compatible with either tea or cola. In addition, alcohol may potentiate some of the pharmacologic effects of risperidone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Risperidone oral solution should not be mixed with tea or cola. It may be taken with water, coffee, orange juice, or lowfat milk. Patients should also be advised to avoid consumption of alcohol.

References

  1. Product Information. Risperdal (risperidone). Janssen Pharmaceuticals. 2001;PROD.

Switch to consumer interaction data

Moderate

venlafaxine food

Applies to: Effexor XR (venlafaxine)

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. 1986;15:31-7.
  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

Switch to consumer interaction data

Moderate

lamoTRIgine food

Applies to: Lamictal (lamotrigine)

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. 1986;15:31-7.
  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

Switch to consumer interaction data

Moderate

cannabis (Schedule I substance) food

Applies to: cannabis

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. 1986;15:31-7.
  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

Switch to consumer interaction data

Minor

ethinyl estradiol food

Applies to: Norinyl 1+35 (ethinyl estradiol / norethindrone)

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References

  1. Weber A, Jager R, Borner A, et al. Can grapefruit juice influence ethinyl estradiol bioavailability? Contraception. 1996;53:41-7.
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T. Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol. Eur J Drug Metab Pharmacokinet. 1995;20:219-24.

Switch to consumer interaction data

Minor

ethinyl estradiol food

Applies to: Norinyl 1+35 (ethinyl estradiol / norethindrone)

The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.

References

  1. Hobbes J, Boutagy J, Shenfield GM. Interactions between ethanol and oral contraceptive steroids. Clin Pharmacol Ther. 1985;38:371-80.

Switch to consumer interaction data

Minor

norethindrone food

Applies to: Norinyl 1+35 (ethinyl estradiol / norethindrone)

The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.

References

  1. Hobbes J, Boutagy J, Shenfield GM. Interactions between ethanol and oral contraceptive steroids. Clin Pharmacol Ther. 1985;38:371-80.

Switch to consumer interaction data

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Central Nervous System (CNS) Drugs

Therapeutic duplication

The recommended maximum number of medicines in the 'Central Nervous System (CNS) Drugs' category to be taken concurrently is usually three. Your list includes five medicines belonging to the 'Central Nervous System (CNS) Drugs' category:

  • cannabis
  • Effexor XR (venlafaxine)
  • Lamictal (lamotrigine)
  • Prozac (fluoxetine)
  • Risperdal (risperidone)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

Duplication

Antidepressants

Therapeutic duplication

The recommended maximum number of medicines in the 'antidepressants' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antidepressants' category:

  • Effexor XR (venlafaxine)
  • Prozac (fluoxetine)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.


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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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Further information

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