Drug General Information (ID: DDISD1GYF4)
  Drug Name Fluoxetine Drug Info Acetazolamide Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Anticonvulsants
  Structure

 Mechanism of Fluoxetine-Acetazolamide Interaction (Severity Level: Moderate)
     Increased risk of hyponatremia Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Fluoxetine Acetazolamide
      Mechanism Hyponatremia Hyponatremia
      Key Mechanism Factor 1
Factor Name Hyponatremia
Factor Description Hyponatremia is a condition in which the amount of sodium in the blood is lower than normal. Symptoms of hyponatremia may include: nausea and vomiting, fatigue, headache or confusion, muscle cramps, weakness, irritability and restlessness.
      Mechanism Description
  • Increased risk of hyponatremia by the combination of Fluoxetine and Acetazolamide 

Recommended Action
      Management Caution is recommended if SSRIs or SNRIs are prescribed in combination with diuretics, particularly in the elderly. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hyponatremia such as nausea, vomiting, headache, malaise, lethargy, irritability, difficulty concentrating, memory impairment, confusion, weakness, muscle spasm, and unsteadiness (which may lead to falls). More severe and/or acute cases may include hallucination, syncope, seizure, coma, respiratory arrest, and death. Discontinuation of SSRI/SNRI therapy should be considered in patients who develop symptomatic hyponatremia, and appropriate medical intervention instituted as necessary. Patients should also have their blood pressure and pulse monitored before and during SSRI/SNRI therapy, especially during the first few weeks and following a dosage increase. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their doctor if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References
1 Product Information. Savella (milnacipran). Forest Pharmaceuticals, St. Louis, MO.
2 Jackson C, Carson W, Markowitz J, Mintzer J "SIADH associated with fluoxetine and sertraline therapy." Am J Psychiatry 152 (1995): 809-10. [PMID: 7726326]
3 Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6. [PMID: 2211552]
4 Kessler J, Samuels SC "Sertraline and hyponatremia." N Engl J Med 335 (1996): 524. [PMID: 8676965]
5 Robinson D, Brooks J, Mahler E, Sheikh JI "SIADH--compulsive drinking or SSRI influence?" Ann Pharmacother 30 (1996): 885. [PMID: 8826582]
6 Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139. [PMID: 2005082]
7 Odeh M, Beny A, Oliven A "Severe symptomatic hyponatremia during citalopram therapy." Am J Med Sci 321 (2001): 159-60. [PMID: 11217819]
8 Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40. [PMID: 11477329]
9 Jacob S, Spinler SA "Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults." Ann Pharmacother 40 (2006): 1618-22. [PMID: 16896026]
10 Vishwanath BM, Navalgund AA, Cusano W, Navalgund KA "Fluoxetine as a cause of SIADH." Am J Psychiatry 148 (1991): 542-3. [PMID: 2006703]
11 Fitzgerald MA "Hyponatremia associated with SSRI use in a 65-year-old woman." Nurse Pract 33 (2008): 11-2. [PMID: 18300778]
12 Product Information. Effexor (venlafaxine). Wyeth-Ayerst Laboratories, Philadelphia, PA.
13 Barclay TS, Lee AJ "Citalopram-associated SIADH." Ann Pharmacother 36 (2002): 1558-63. [PMID: 12243606]
14 Product Information. Cymbalta (duloxetine). Lilly, Eli and Company, Indianapolis, IN.
15 Product Information. Viibryd (vilazodone). Trovis Pharmaceuticals LLC, New Haven, CT.
16 van Campen JP, Voets AJ "SIADH caused by paroxetine." Ann Pharmacother 30 (1996): 1499. [PMID: 8968470]
17 Product Information. Celexa (citalopram). Forest Pharmaceuticals, St. Louis, MO.
18 Baliga RR, McHardy KC. Syndrome of inappropriate antidiuretic hormone secretion due to fluvoxamine therapy [published correction appears in Br J Clin Pract 1993 May-Jun;47(3):119].?Br J Clin Pract. 1993;47(2):62-63. [PMID: 8334062]
19 Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75. [PMID: 15320756]
20 Spigset O, hedenmalm K "Hyponatremia in relation to treatment with antidepressants: a survey of reports in the World Health Organization data base for spontaneous reporting of adverse drug reactions." Pharmacotherapy 17 (1997): 348-52. [PMID: 9085327]
21 Crews JR, Potts NL, Schreiber J, Lipper S "Hyponatremia in a patient treated with sertraline." Am J Psychiatry 150 (1993): 1564. [PMID: 8379571]
22 Staab JP, Yerkes SA, Cheney EM, Clayton AH "Transient SIADH associated with fluoxetine." Am J Psychiatry 147 (1990): 1569-70. [PMID: 2221175]
23 Odeh M, Seligmann H, Oliven A "Severe life-threatening hyponatremia during paroxetine therapy." J Clin Pharmacol 39 (1999): 1290-1. [PMID: 10586396]
24 Bouman WP, Johnson H, TrescoliSerrano C, Jones RG "Recurrent hyponatremia associated with sertraline and lofepramine." Am J Psychiatry 154 (1997): 580. [PMID: 9090354]
25 Girault C, Richard JC, Chevron V, Goulle JP, Droy JM, Bonmarchand G, Leroy J "Syndrome of inappropriate secretion of antidiuretic hormone in two elderly women with elevated serum fluoxetine." J Toxicol Clin Toxicol 35 (1997): 93-5. [PMID: 9022659]
26 Product Information. Lexapro (escitalopram). Forest Pharmaceuticals, St. Louis, MO.
27 Bradley ME, Foote EF, Lee EN, Merkle L "Sertraline-associated syndrome of inappropriate antidiuretic hormone: case report and review of the literature." Pharmacotherapy 16 (1996): 680-3. [PMID: 8840376]
28 Hwang AS, Magraw RM "Syndrome of inappropriate secretion of antidiuretic hormone due to fluoxetine." Am J Psychiatry 146 (1989): 399. [PMID: 2784038]
29 Ayonrinde OT, Sanfilippo FM "SSRI antidepressants and SIADH." Aust N Z J Psychiatry 31 (1997): 306-7. [PMID: 9140643]
30 Product Information. Fetzima (levomilnacipran). Forest Pharmaceuticals, St. Louis, MO.
31 Thornton SL, Resch DS "SIADH associated with sertraline therapy." Am J Psychiatry 152 (1995): 809. [PMID: 7726325]
32 Kazal LA, Jr Hall DL, Miller LG, Noel ML "Fluoxetine-induced SIADH: a geriatric occurrence?" J Fam Pract 36 (1993): 341-3. [PMID: 8454983]
33 Cohen BJ, Mahelsky M, Adler L "More cases of SIADH with fluoxetine." Am J Psychiatry 147 (1990): 948-9. [PMID: 2356883]
34 Ayonrinde OT, Reutens SG, Sanfilippo FM "Paroxetine-induced SIADH." Med J Aust 163 (1995): 390. [PMID: 7565274]
35 Chua TP, Vong SK "Hyponatraemia associated with paroxetine." BMJ 306 (1993): 143. [PMID: 8435627]
36 Product Information. Paxil (paroxetine). GlaxoSmithKline, Research Triangle Park, NC.
37 Selective serotonin reuptake inhibitors and SIADH. Med J Aust 164 (1996): 562. [PMID: 8649298]
38 Goddard C, Paton C "Hyponatraemia associated with paroxetine." BMJ 305 (1992): 1332. [PMID: 1483080]
39 Product Information. Brintellix (vortioxetine). Takeda Pharmaceuticals America, Lincolnshire, IL.
40 Covyeou JA, Jackson CW "Hyponatremia associated with escitalopram." N Engl J Med 356 (2007): 94-5. [PMID: 17202465]
41 Woo MH, Smythe MA "Association of SIADH with selective serotonin reuptake inhibitors." Ann Pharmacother 31 (1997): 108-10. [PMID: 8997475]
42 Llorente MD, Gorelick M, Silverman MA "Sertraline as the cause of inappropriate antidiuretic hormone secretion." J Clin Psychiatry 55 (1994): 543-4. [PMID: 7814351]
43 Product Information. Luvox (fluvoxamine). Solvay Pharmaceuticals Inc, Marietta, GA.
44 Blacksten JV, Birt JA "Syndrome of inappropriate secretion of antidiuretic hormone secondary to fluoxetine." Ann Pharmacother 27 (1993): 723-4. [PMID: 8329791]
45 Schattner A, Skurnik Y "Fluoxetine-induced SIADH." J Am Geriatr Soc 44 (1996): 1413. [PMID: 8909370]
46 Product Information. Prozac (fluoxetine). Dista Products Company, Indianapolis, IN.
47 Product Information. Pristiq (desvenlafaxine). Wyeth Laboratories, Philadelphia, PA.
48 Rosner MH "Severe hyponatremia associated with the combined use of thiazide diuretics and selective serotonin reuptake inhibitors." Am J Med Sci 327 (2004): 109-11. [PMID: 14770031]
49 Doshi D, Borison R "Association of transient SIADH with sertraline." Am J Psychiatry 151 (1994): 779-80. [PMID: 8166325]
50 Product Information. Zoloft (sertraline). Roerig Division, New York, NY.
51 Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595. [PMID: 9518913]
52 Esposito P, Rampino T, Gregorini M, et al. "Severe symptomatic hyponatremia during sibutramine therapy: a case report." Am J Kidney Dis 52 (2008): 137-9. [PMID: 18487000]
53 Madhusoodanan S, Brenner R, Brafman I, Bogunovic O "Hyponatremia associated with paroxetine use." South Med J 92 (1999): 843. [PMID: 10456732]
54 Spier SA, Frontera MA "Unexpected deaths in depressed medical inpatients treated with fluoxetine." J Clin Psychiatry 52 (1991): 377-82. [PMID: 1894590]