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Drug Interactions between Bufferin Arthritis Strength and Savella

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

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Interactions between your drugs

Moderate

aspirin milnacipran

Applies to: Bufferin Arthritis Strength (aspirin) and Savella (milnacipran)

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

Moderate

milnacipran food

Applies to: Savella (milnacipran)

GENERALLY AVOID: Use of milnacipran in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Milnacipran alone can increase serum transaminase levels. In placebo-controlled fibromyalgia trials, increases in ALT were more frequently observed in patients treated with milnacipran 100 mg/day (6%) and 200 mg/day (7%) compared to patients treated with placebo (3%). One patient receiving milnacipran 100 mg/day (0.2%) had an increase in ALT greater than 5 times the upper limit of normal (ULN) but did not exceed 10 times the ULN. Increases in AST were also more frequently observed in patients treated with milnacipran 100 mg/day (3%) and 200 mg/day (5%) than in patients treated with placebo (2%). There have been reported cases of increased liver enzymes and severe liver injury, including fulminant hepatitis, from foreign postmarketing experience with milnacipran. Significant underlying clinical conditions and/or use of multiple concomitant medications were present in the cases of severe liver injury.

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

References

  1. (2009) "Product Information. Savella (milnacipran)." Forest Pharmaceuticals

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Moderate

aspirin food

Applies to: Bufferin Arthritis Strength (aspirin)

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

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Minor

aspirin food

Applies to: Bufferin Arthritis Strength (aspirin)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6

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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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