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Drug Interactions between Anafranil and Durlaza

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

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Interactions between your drugs

Moderate

aspirin clomiPRAMINE

Applies to: Durlaza (aspirin) and Anafranil (clomipramine)

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 "Bleeding, a side effect of fluoxetine." Am J Psychiatry 149 (1992): 412
  2. Claire RJ, Servis ME, Cram DL Jr "Potential interaction between warfarin sodium and fluoxetine." Am J Psychiatry 148 (1991): 1604
  3. Yaryura-Tobias JA, Kirschen H, Ninan P, Mosberg HJ "Fluoxetine and bleeding in obsessive-compulsive disorder." Am J Psychiatry 148 (1991): 949
  4. Humphries JE, Wheby MS, VandenBerg SR "Fluoxetine and the bleeding time." Arch Pathol Lab Med 114 (1990): 727-8
  5. Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9
  6. Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol 10 (1990): 213-7
  7. "Product Information. Zoloft (sertraline)." Roerig Division PROD (2001):
  8. Woolfrey S, Gammack NS, Dewar MS, Brown PJ "Fluoxetine-warfarin interaction." BMJ 307 (1993): 241
  9. "Product Information. Prozac (fluoxetine)." Dista Products Company PROD (2001):
  10. "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories PROD (2001):
  11. Bannister SJ, Houser VP, Hulse JD, Kisicki JC, Rasmussen JG "Evaluation of the potential for interactions of paroxetine with diazepam, cimetidine, warfarin, and digoxin." Acta Psychiatr Scand Suppl 350 (1989): 102-6
  12. "Product Information. Paxil (paroxetine)." GlaxoSmithKline PROD (2001):
  13. Messiha FS "Fluoxetine - adverse effects and drug-drug interactions." J Toxicol Clin Toxicol 31 (1993): 603-30
  14. Ottervanger JP, Stricker BH, Huls J, Weeda JN "Bleeding attributed to the intake of paroxetine." Am J Psychiatry 151 (1994): 781-2
  15. "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc PROD (2001):
  16. Krivy J, Wiener J "Sertraline and platelet counts in idiopathic thrombocytopenia purpura." Lancet 345 (1995): 132
  17. Skop BP, Brown TM "Potential vascular and bleeding complications of treatment with selective serotonin reuptake inhibitors." Psychosomatics 37 (1996): 12-6
  18. Pai VB, Kelly MW "Bruising associated with the use of fluoxetine." Ann Pharmacother 30 (1996): 786-8
  19. Alderman CP, Seshadri P, Ben-Tovim DI "Effects of serotonin reuptake inhibitors on hemostasis." Ann Pharmacother 30 (1996): 1232-4
  20. Leung M, Shore R "Fluvoxamine-associated bleeding." Can J Psychiatry 41 (1996): 604-5
  21. Dent LA, Orrock MW "Warfarin-fluoxetine and diazepam-fluoxetine interaction." Pharmacotherapy 17 (1997): 170-2
  22. Ford MA, Anderson ML, Rindone JP, Jaskar DW "Lack of effect of fluoxetine on the hypoprothrombinemic response of warfarin." J Clin Psychopharmacol 17 (1997): 110-2
  23. "Product Information. Celexa (citalopram)." Forest Pharmaceuticals PROD (2001):
  24. de Abajo FJ, Rodriguez LA, Montero D "Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study." BMJ 319 (1999): 1106-9
  25. de Abajo FJ, Jick H, Derby L, Jick S, Schmitz S "Intracranial haemorrhage and use of selective serotonin reuptake inhibitors." Br J Clin Pharmacol 50 (2000): 43-7
  26. Settle EC "Antidepressant drugs: disturbing and potentially dangerous adverse effects." J Clin Psychiatry 59 Suppl 16 (1998): 25-30
  27. Hergovich N, Aigner M, Eichler HG, Entlicher J, Drucker C, Jilma B "Paroxetine decreases platelet serotonin storage and platelet function in human beings." Clin Pharmacol Ther 68 (2000): 435-42
  28. Layton D, Clark DWJ, Pearce GL, Shakir SAW "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 (2001): 167-76
  29. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals (2002):
  30. de Maistre E, Allart C, Lecompte T, Bollaert PE "Severe bleeding associated with use of low molecular weight heparin and selective serotonin reuptake inhibitors." Am J Med 113 (2002): 530-2
  31. Dalton SO, Johansen C, Mellemkjaer L, Norgard B, Sorensen HT, Olsen JH "Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study." Arch Intern Med 163 (2003): 59-64
  32. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):
  33. Tata LJ, Fortun PJ, Hubbard RB, et al. "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 (2005): 175-81
  34. Cerner Multum, Inc. "Australian Product Information." O 0
  35. "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories (2008):
  36. "Product Information. Savella (milnacipran)." Forest Pharmaceuticals (2009):
  37. "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC (2011):
  38. "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals (2013):
  39. "Product Information. Brintellix (vortioxetine)." Takeda Pharmaceuticals America (2013):
View all 39 references

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Drug and food interactions

Moderate

clomiPRAMINE food

Applies to: Anafranil (clomipramine)

MONITOR: Limited data suggest that the administration of clomipramine with grapefruit juice or cranberry juice may significantly increase plasma drug concentrations of clomipramine. Clomipramine is initially demethylated by CYP450 1A2, 3A3 and 3A4 before undergoing further metabolism to 8-hydroxyclomipramine. The increase in clomipramine bioavailability may stem from inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The precise mechanism by which cranberry juice exerts its effects is unknown, but may involve inhibition of CYP450 isoenzymes. This interaction has occasionally been exploited in attempts to improve symptomatic control of obsessive compulsive disorder.

MANAGEMENT: Patients receiving clomipramine therapy who ingest cranberry juice, grapefruits, or grapefruit juice should be monitored for adverse effects and undue fluctuations in plasma drug levels.

References

  1. Oesterheld J, Kallepalli BR "Grapefruit juice and clomipramine: shifting metabolitic ratios." J Clin Psychopharmacol 17 (1997): 62-3
  2. 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 68 (2000): 468-77
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Cerner Multum, Inc. "Australian Product Information." O 0
View all 4 references

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Moderate

aspirin food

Applies to: Durlaza (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. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn PROD (2002):

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Moderate

clomiPRAMINE food

Applies to: Anafranil (clomipramine)

GENERALLY AVOID: The combination of ethanol and a tricyclic antidepressant may result in additive impairment of motor skills, especially driving skills. Also, one study has suggested that clomipramine metabolism is significantly impaired for several weeks or more following discontinuation of chronic alcohol consumption.

MANAGEMENT: Patients should be warned of this interaction and advised to limit their ethanol intake while taking tricyclic antidepressants. Monitoring for TCA toxicity (CNS depression, excessive anticholinergic effects, hypotension, arrhythmias) is recommended during alcohol withdrawal.

References

  1. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther 17 (1975): 515-22
  2. Berlin I, Cournot A, Zimmer R, et al. "Evaluation and comparison of the interaction between alcohol and moclobemide or clomipramine in healthy subjects." Psychopharmacology (Berl) 100 (1990): 40-5
  3. Balant-Gorgia AE, Gay M, Gex-Fabry M, Balant LP "Persistent impairment of clomipramine demethylation in recently detoxified alcoholic patients." Ther Drug Monit 14 (1992): 119-24

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Minor

aspirin food

Applies to: Durlaza (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 "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet 11 (1986): 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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