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Drug Interactions between fluvoxamine and nebivolol / valsartan

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

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Interactions between your drugs

Moderate

fluvoxaMINE nebivolol

Applies to: fluvoxamine and nebivolol / valsartan

MONITOR: Limited clinical data suggest that selective serotonin reuptake inhibitors (SSRIs) may potentiate the pharmacologic effects of some beta-blockers. There have been case reports of patients stabilized on beta-blocker therapy who developed bradycardia, hypotension, and complete heart block following the addition of a SSRI, subsequently requiring discontinuation of one or both agents and/or institution of a permanent pacemaker. The interaction is also corroborated by data from in vitro and clinical studies involving paroxetine and metoprolol conducted by one group of investigators. The proposed mechanism is SSRI inhibition (competitive and/or noncompetitive) of CYP450 2D6, the isoenzyme responsible for the metabolic clearance of beta-blockers such as carvedilol, labetalol, metoprolol, nebivolol, propranolol, and timolol. Paroxetine and norfluoxetine (the active metabolite of fluoxetine), in particular, are potent inhibitors of CYP450 2D6 and may be more likely than other SSRIs to cause the interaction. On the other hand, fluvoxamine is a potent inhibitor of CYP450 1A2 and may significantly interact with propranolol, which is a substrate of both CYP450 2D6 and 1A2.

MANAGEMENT: During concomitant therapy with SSRIs, a lower initial dosage and more cautious titration of the beta-blocker may be appropriate. Cardiac function should be closely monitored and the beta-blocker dosage adjusted accordingly, particularly following initiation, discontinuation or change of dosage of SSRI in patients who are stabilized on their beta-blocker regimen. Due to the long half-life of fluoxetine and its active metabolite, norfluoxetine, the risk of an interaction may exist for an extended period (up to several weeks) after discontinuation of fluoxetine. To avoid the interaction, use of beta-blockers that are primarily eliminated by the kidney such as atenolol, acebutolol, betaxolol, carteolol, and nadolol may be considered.

References

  1. Walley T, Pirmohamed M, Proudlove C, Maxwell D (1993) "Interaction of metoprolol and fluoxetine." Lancet, 341, p. 967-8
  2. Otton SV, Wu D, Joffe RT, Cheung SW, Sellers EM (1993) "Inhibition by fluoxetine of cytochrome P450 2D6 activity." Clin Pharmacol Ther, 53, p. 401-9
  3. Brosen K, Skjelbo E, Rasmussen BB, Poulsen HE, Loft S (1993) "Fluvoxamine is a potent inhibitor of cytochrome P4501A2." Biochem Pharmacol, 45, p. 1211-4
  4. 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.
  5. Drake WM, Gordon GD (1994) "Heart block in a patient on propranolol and fluoxetine." Lancet, 343, p. 425-6
  6. Perucca E, Gatti G, Spina E (1994) "Clinical pharmacokinetics of fluvoxamine." Clin Pharmacokinet, 27, p. 175-90
  7. Crewe HK, Lennard MS, Tucker GT, Woods FR, Haddock RE (1992) "The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes." Br J Clin Pharmacol, 34, p. 262-5
  8. (2001) "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc
  9. Riesenman C (1995) "Antidepressant drug interactions and the cytochrome p450 system: a critical appraisal." Pharmacotherapy, 15, s84-99
  10. Nemeroff CB, Devane CL, Pollock BG (1996) "Newer antidepressants and the cytochrome p450 system." Am J Psychiatry, 153, p. 311-20
  11. Ereshefsky L (1996) "Treating depression: potential drug-drug interactions: commentary." J Clin Psychopharmacol, 16 (suppl, s50-3
  12. Richelson E (1998) "Pharmacokinetic interactions of antidepressants." J Clin Psychiatry, 59, p. 22-6
  13. Kashuba ADM, Nafziger AN, Kearns GL, Leeder JS, Gotschall R, Rocci ML, Kulawy RW, Beck DJ, Bertino JS (1998) "Effect of fluvoxamine therapy on the activities of CYP1A2, CYP2D6, and CYP3A as determined by phenotyping." Clin Pharmacol Ther, 64, p. 257-68
  14. Hemeryck A, Lefebvre RA, DeVriendt C, Belpaire FM (2000) "Paroxetine affects metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers." Clin Pharmacol Ther, 67, p. 283-91
  15. Amchin J, Ereshefsky L, Zarycranski W, Taylor K, Albano D, Klockowski PM (2001) "Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan, a CYP2D6 probe." J Clin Pharmacol, 41, p. 443-51
  16. Hemeryck A, DeVriendt CA, Belpaire FM (2001) "Metoprolol-paroxetine interaction in human liver microsomes: Stereoselective aspects and prediction of the in vivo interaction." Drug Metab Disposition, 29, p. 656-63
View all 16 references

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Moderate

valsartan nebivolol

Applies to: nebivolol / valsartan and nebivolol / valsartan

GENERALLY AVOID: In the Valsartan Heart Failure Trial, the combination of valsartan with a beta-blocker and an ACE inhibitor was associated with unfavorable outcomes on morbidity and mortality in heart failure patients. The mechanism is unknown.

MANAGEMENT: The manufacturer recommends that the triple combination of valsartan with a beta-blocker and an ACE inhibitor be avoided in heart failure patients.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."

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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

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

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Moderate

valsartan food

Applies to: nebivolol / valsartan

GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

References

  1. (2001) "Product Information. Cozaar (losartan)." Merck & Co., Inc
  2. (2001) "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

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

See also

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Drug Interaction Classification

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

Further information

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

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