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Drug Interactions between avapritinib and fluvoxamine

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

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Interactions between your drugs

Moderate

fluvoxaMINE avapritinib

Applies to: fluvoxamine and avapritinib

MONITOR: Serotonin reuptake inhibitors (SRIs) may potentiate the risk of bleeding in patients treated with ulcerogenic agents and agents that affect hemostasis such as anticoagulants, platelet inhibitors, thrombin inhibitors, thrombolytic agents, or agents that commonly cause thrombocytopenia. The tricyclic antidepressant, clomipramine, is also a strong SRI and may interact similarly. Serotonin release by platelets plays an important role in hemostasis, thus SRIs may alter platelet function and induce bleeding. Published case reports have documented the occurrence of bleeding episodes in patients treated with psychotropic agents that interfere with serotonin reuptake. Bleeding events related to SRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Additional epidemiological studies have confirmed the association between use of these agents and the occurrence of upper gastrointestinal bleeding, and concurrent use of NSAIDs or aspirin was found to potentiate the risk. Preliminary data also suggest that there may be a pharmacodynamic interaction between SSRIs and oral anticoagulants that can cause an increased bleeding diathesis. Concomitant administration of paroxetine and warfarin, specifically, has been associated with an increased frequency of bleeding without apparent changes in the disposition of either drug or changes in the prothrombin time. Bleeding has also been reported with fluoxetine and warfarin, while citalopram and sertraline have been reported to prolong the prothrombin time of patients taking warfarin by about 5% to 8%. In the RE-LY study (Randomized Evaluation of Long-term anticoagulant therapy), SRIs were associated with an increased risk of bleeding in all treatment groups.

MANAGEMENT: Caution is advised if SRIs or clomipramine are used in combination with other drugs that affect hemostasis. Close clinical and laboratory observation for hematologic complications is recommended. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

References

  1. Aranth J, Lindberg C (1992) "Bleeding, a side effect of fluoxetine." Am J Psychiatry, 149, p. 412
  2. Claire RJ, Servis ME, Cram DL Jr (1991) "Potential interaction between warfarin sodium and fluoxetine." Am J Psychiatry, 148, p. 1604
  3. Yaryura-Tobias JA, Kirschen H, Ninan P, Mosberg HJ (1991) "Fluoxetine and bleeding in obsessive-compulsive disorder." Am J Psychiatry, 148, p. 949
  4. Humphries JE, Wheby MS, VandenBerg SR (1990) "Fluoxetine and the bleeding time." Arch Pathol Lab Med, 114, p. 727-8
  5. Alderman CP, Moritz CK, Ben-Tovim DI (1992) "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother, 26, p. 1517-9
  6. Ciraulo DA, Shader RI (1990) "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol, 10, p. 213-7
  7. (2001) "Product Information. Zoloft (sertraline)." Roerig Division
  8. Woolfrey S, Gammack NS, Dewar MS, Brown PJ (1993) "Fluoxetine-warfarin interaction." BMJ, 307, p. 241
  9. (2001) "Product Information. Prozac (fluoxetine)." Dista Products Company
  10. (2001) "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories
  11. Bannister SJ, Houser VP, Hulse JD, Kisicki JC, Rasmussen JG (1989) "Evaluation of the potential for interactions of paroxetine with diazepam, cimetidine, warfarin, and digoxin." Acta Psychiatr Scand Suppl, 350, p. 102-6
  12. (2001) "Product Information. Paxil (paroxetine)." GlaxoSmithKline
  13. Messiha FS (1993) "Fluoxetine - adverse effects and drug-drug interactions." J Toxicol Clin Toxicol, 31, p. 603-30
  14. Ottervanger JP, Stricker BH, Huls J, Weeda JN (1994) "Bleeding attributed to the intake of paroxetine." Am J Psychiatry, 151, p. 781-2
  15. (2001) "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc
  16. Krivy J, Wiener J (1995) "Sertraline and platelet counts in idiopathic thrombocytopenia purpura." Lancet, 345, p. 132
  17. Skop BP, Brown TM (1996) "Potential vascular and bleeding complications of treatment with selective serotonin reuptake inhibitors." Psychosomatics, 37, p. 12-6
  18. Pai VB, Kelly MW (1996) "Bruising associated with the use of fluoxetine." Ann Pharmacother, 30, p. 786-8
  19. Alderman CP, Seshadri P, Ben-Tovim DI (1996) "Effects of serotonin reuptake inhibitors on hemostasis." Ann Pharmacother, 30, p. 1232-4
  20. Leung M, Shore R (1996) "Fluvoxamine-associated bleeding." Can J Psychiatry, 41, p. 604-5
  21. Dent LA, Orrock MW (1997) "Warfarin-fluoxetine and diazepam-fluoxetine interaction." Pharmacotherapy, 17, p. 170-2
  22. Ford MA, Anderson ML, Rindone JP, Jaskar DW (1997) "Lack of effect of fluoxetine on the hypoprothrombinemic response of warfarin." J Clin Psychopharmacol, 17, p. 110-2
  23. (2001) "Product Information. Celexa (citalopram)." Forest Pharmaceuticals
  24. de Abajo FJ, Rodriguez LA, Montero D (1999) "Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study." BMJ, 319, p. 1106-9
  25. de Abajo FJ, Jick H, Derby L, Jick S, Schmitz S (2000) "Intracranial haemorrhage and use of selective serotonin reuptake inhibitors." Br J Clin Pharmacol, 50, p. 43-7
  26. Settle EC (1998) "Antidepressant drugs: disturbing and potentially dangerous adverse effects." J Clin Psychiatry, 59 Suppl 16, p. 25-30
  27. Hergovich N, Aigner M, Eichler HG, Entlicher J, Drucker C, Jilma B (2000) "Paroxetine decreases platelet serotonin storage and platelet function in human beings." Clin Pharmacol Ther, 68, p. 435-42
  28. Layton D, Clark DWJ, Pearce GL, Shakir SAW (2001) "Is there an association between selective serotonin reuptake inhibitors and risk of abnormal bleeding? Results from a cohort study based on prescription event monitoring in England." Eur J Clin Pharmacol, 57, p. 167-76
  29. (2002) "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals
  30. de Maistre E, Allart C, Lecompte T, Bollaert PE (2002) "Severe bleeding associated with use of low molecular weight heparin and selective serotonin reuptake inhibitors." Am J Med, 113, p. 530-2
  31. Dalton SO, Johansen C, Mellemkjaer L, Norgard B, Sorensen HT, Olsen JH (2003) "Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study." Arch Intern Med, 163, p. 59-64
  32. (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company
  33. Tata LJ, Fortun PJ, Hubbard RB, et al. (2005) "Does concurrent prescription of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs substantially increase the risk of upper gastrointestinal bleeding?" Aliment Pharmacol Ther, 22, p. 175-81
  34. Cerner Multum, Inc. "Australian Product Information."
  35. (2008) "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories
  36. (2009) "Product Information. Savella (milnacipran)." Forest Pharmaceuticals
  37. (2011) "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC
  38. (2013) "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals
  39. (2013) "Product Information. Brintellix (vortioxetine)." Takeda Pharmaceuticals America
View all 39 references

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Drug and food interactions

Major

avapritinib food

Applies to: avapritinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of avapritinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. Based on pharmacokinetic modeling, administration of avapritinib (300 mg once daily) in combination with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily) is predicted to increase avapritinib systemic exposure (AUC) by 600% at steady state, while administration with the moderate CYP450 3A4 inhibitor fluconazole (200 mg once daily) is predicted to increase avapritinib systemic exposure (AUC) by 210% at steady state. 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. Increased exposure to avapritinib may increase the risk and/or severity of serious adverse effects such as intracranial hemorrhage, cognitive impairment, mood disorders, hallucinations, edema, and decreases in hemoglobin, leukocytes, neutrophils, and platelets.

ADJUST DOSING INTERVAL: Food may increase the oral absorption of avapritinib. When avapritinib was administered with a high-calorie, high-fat meal (approximately 909 calories; 58 g carbohydrate, 56 g fat, 43 g protein), avapritinib Cmax and AUC increased by 59% and 29%, respectively, compared to administration in the fasted state.

MANAGEMENT: Avapritinib should be administered on an empty stomach at least 1 hour before or 2 hours after a meal. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with avapritinib.

References

  1. (2020) "Product Information. Ayvakit (avapritinib)." Blueprint Medicines Corporation

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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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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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