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Drug Interactions between duloxetine and fluvoxamine

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

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Interactions between your drugs

Major

fluvoxaMINE DULoxetine

Applies to: fluvoxamine and duloxetine

GENERALLY AVOID: Coadministration with fluvoxamine may significantly increase the plasma concentrations of duloxetine. The mechanism is fluvoxamine inhibition of duloxetine metabolism via CYP450 1A2. In 14 male study subjects, fluvoxamine caused a 2.5-fold increase in duloxetine peak plasma concentration (Cmax), a nearly 6-fold increase in duloxetine systemic exposure (AUC), and an approximately 3-fold increase in duloxetine half-life. High plasma levels of duloxetine may increase the risk of serious cardiovascular effects such as hypertension, hypertensive crisis, increased heart rate, orthostatic hypotension, and syncope. In addition, the risk of serotonin syndrome may be potentiated, not just due to elevated levels of duloxetine but also because of additive serotonergic effects from coadministration with fluvoxamine, an SSRI. Serotonin syndrome is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms may include mental status changes such as irritability, altered consciousness, confusion, hallucinations, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: Concomitant use of duloxetine with fluvoxamine should be avoided.

References (10)
  1. Nierenberg DW, Semprebon M (1993) "The central nervous system serotonin syndrome." Clin Pharmacol Ther, 53, p. 84-8
  2. Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
  3. Insel TR, Roy BF, Cohen RM, Murphy DL (1982) "Possible development of the serotonin syndrome in man." Am J Psychiatry, 139, p. 954-5
  4. Fischer P (1995) "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol, 15, p. 440-2
  5. Corkeron MA (1995) "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust, 163, p. 481-2
  6. Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
  7. Nijhawan PK, Katz G, Winter S (1996) "Psychiatric illness and the serotonin syndrome: an emerging adverse drug effect leading to intensive care unit admission." Crit Care Med, 24, p. 1086-9
  8. Mackay FJ, Dunn NR, Mann RD (1999) "Antidepressants and the serotonin syndrome in general practice." Br J Gen Pract, 49, p. 871-4
  9. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
  10. (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company

Drug and food interactions

Moderate

fluvoxaMINE food

Applies to: fluvoxamine

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

DULoxetine food

Applies to: duloxetine

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

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

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

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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