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7 Interactions found for:

Cymbalta and hydrochlorothiazide
Interactions Summary
  • 4 Major
  • 3 Moderate
  • 0 Minor
  • Cymbalta
  • hydrochlorothiazide

Drug Interactions

Moderate
Hydrochlorothiazide + Cymbalta

The following applies to the ingredients: Hydrochlorothiazide and Duloxetine (found in Cymbalta)

MONITOR: Coadministration with diuretics may potentiate the risk of hyponatremia associated with the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). The mechanism by which SSRIs and SNRIs produce hyponatremia has not been clearly established. In many cases, the hyponatremia appears to be secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Cases with serum sodium lower than 110 mmol/L have been reported. These events are generally reversible following discontinuation of therapy and/or medical intervention. Elderly patients and patients taking diuretics or who are otherwise volume-depleted may be at greater risk of developing hyponatremia with SSRIs and SNRIs.

MONITOR: Antihypertensive agents such as diuretics may potentiate the orthostatic effect that is occasionally observed upon the initiation of SSRI or SNRI therapy. Syncope and orthostatic hypotension tend to occur within the first week of SNRI/SSRI therapy but can occur at any time during treatment, particularly after a dosage increase. The use of SSRIs or SNRIs may also cause sustained increases in blood pressure and heart rate, which may antagonize the therapeutic effects of antihypertensive medications. Cases of elevated blood pressure requiring immediate treatment have been reported in postmarketing experience.

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. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them. Dose reduction or drug discontinuation should be considered in patients who experience a sustained increase in blood pressure or pulse rate during SSRI or SNRI therapy.

References

  1. Hwang AS, Magraw RM "Syndrome of inappropriate secretion of antidiuretic hormone due to fluoxetine." Am J Psychiatry 146 (1989): 399
  2. Vishwanath BM, Navalgund AA, Cusano W, Navalgund KA "Fluoxetine as a cause of SIADH." Am J Psychiatry 148 (1991): 542-3
  3. Staab JP, Yerkes SA, Cheney EM, Clayton AH "Transient SIADH associated with fluoxetine." Am J Psychiatry 147 (1990): 1569-70
  4. Cohen BJ, Mahelsky M, Adler L "More cases of SIADH with fluoxetine." Am J Psychiatry 147 (1990): 948-9
  5. Spier SA, Frontera MA "Unexpected deaths in depressed medical inpatients treated with fluoxetine." J Clin Psychiatry 52 (1991): 377-82
  6. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  7. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  8. Kazal LA, Jr Hall DL, Miller LG, Noel ML "Fluoxetine-induced SIADH: a geriatric occurrence?" J Fam Pract 36 (1993): 341-3
  9. Crews JR, Potts NL, Schreiber J, Lipper S "Hyponatremia in a patient treated with sertraline." Am J Psychiatry 150 (1993): 1564
  10. Blacksten JV, Birt JA "Syndrome of inappropriate secretion of antidiuretic hormone secondary to fluoxetine." Ann Pharmacother 27 (1993): 723-4
  11. "Product Information. Zoloft (sertraline)." Roerig Division PROD (2001):
  12. "Product Information. Prozac (fluoxetine)." Dista Products Company PROD (2001):
  13. "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories PROD (2001):
  14. Chua TP, Vong SK "Hyponatraemia associated with paroxetine." BMJ 306 (1993): 143
  15. Goddard C, Paton C "Hyponatraemia associated with paroxetine." BMJ 305 (1992): 1332
  16. "Product Information. Paxil (paroxetine)." GlaxoSmithKline PROD (2001):
  17. Doshi D, Borison R "Association of transient SIADH with sertraline." Am J Psychiatry 151 (1994): 779-80
  18. Baliga RR, McHardy KC "Syndrome of inappropriate antidiuretic hormone secretion due to fluvoxamine therapy [published erratum appears in Br J Clin Pract 1993 May-Jun;47(3):119]." Br J Clin Pract 47 (1993): 62-3
  19. "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc PROD (2001):
  20. Llorente MD, Gorelick M, Silverman MA "Sertraline as the cause of inappropriate antidiuretic hormone secretion." J Clin Psychiatry 55 (1994): 543-4
  21. Thornton SL, Resch DS "SIADH associated with sertraline therapy." Am J Psychiatry 152 (1995): 809
  22. Jackson C, Carson W, Markowitz J, Mintzer J "SIADH associated with fluoxetine and sertraline therapy." Am J Psychiatry 152 (1995): 809-10
  23. Ayonrinde OT, Reutens SG, Sanfilippo FM "Paroxetine-induced SIADH." Med J Aust 163 (1995): 390
  24. Kessler J, Samuels SC "Sertraline and hyponatremia." N Engl J Med 335 (1996): 524
  25. 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
  26. "Selective serotonin reuptake inhibitors and SIADH." Med J Aust 164 (1996): 562
  27. Robinson D, Brooks J, Mahler E, Sheikh JI "SIADH--compulsive drinking or SSRI influence?" Ann Pharmacother 30 (1996): 885
  28. Schattner A, Skurnik Y "Fluoxetine-induced SIADH." J Am Geriatr Soc 44 (1996): 1413
  29. van Campen JP, Voets AJ "SIADH caused by paroxetine." Ann Pharmacother 30 (1996): 1499
  30. Woo MH, Smythe MA "Association of SIADH with selective serotonin reuptake inhibitors." Ann Pharmacother 31 (1997): 108-10
  31. 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
  32. Bouman WP, Johnson H, TrescoliSerrano C, Jones RG "Recurrent hyponatremia associated with sertraline and lofepramine." Am J Psychiatry 154 (1997): 580
  33. 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
  34. Ayonrinde OT, Sanfilippo FM "SSRI antidepressants and SIADH." Aust N Z J Psychiatry 31 (1997): 306-7
  35. "Product Information. Celexa (citalopram)." Forest Pharmaceuticals PROD (2001):
  36. Madhusoodanan S, Brenner R, Brafman I, Bogunovic O "Hyponatremia associated with paroxetine use." South Med J 92 (1999): 843
  37. Odeh M, Seligmann H, Oliven A "Severe life-threatening hyponatremia during paroxetine therapy." J Clin Pharmacol 39 (1999): 1290-1
  38. Odeh M, Beny A, Oliven A "Severe symptomatic hyponatremia during citalopram therapy." Am J Med Sci 321 (2001): 159-60
  39. 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
  40. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals (2002):
  41. Barclay TS, Lee AJ "Citalopram-associated SIADH." Ann Pharmacother 36 (2002): 1558-63
  42. 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
  43. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):
  44. Jacob S, Spinler SA "Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults." Ann Pharmacother 40 (2006): 1618-22
  45. Covyeou JA, Jackson CW "Hyponatremia associated with escitalopram." N Engl J Med 356 (2007): 94-5
  46. "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories (2008):
  47. Fitzgerald MA "Hyponatremia associated with SSRI use in a 65-year-old woman." Nurse Pract 33 (2008): 11-2
  48. 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
  49. "Product Information. Savella (milnacipran)." Forest Pharmaceuticals (2009):
  50. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  51. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595
  52. "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC (2011):
  53. "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals (2013):
  54. "Product Information. Brintellix (vortioxetine)." Takeda Pharmaceuticals America (2013):

Drug and Food Interactions

Moderate
Cymbalta + Food

The following applies to the ingredients: Duloxetine (found in Cymbalta)

GENERALLY AVOID: Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

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

References

  1. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):

Moderate
Hydrochlorothiazide + Food

The following applies to the ingredients: Hydrochlorothiazide

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. 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
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595

Drug and Pregnancy Interactions

The following applies to the ingredients: Hydrochlorothiazide

The manufacturer recommends that hydrochlorothiazide should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.

AU TGA pregnancy category: C
US FDA pregnancy category: B

The routine use of diuretics during pregnancy is not indicated or recommended.

Animal studies have failed to reveal evidence of fetal harm. There are no data from controlled human studies, but retrospective reviews have shown an increased risk of malformations associated with thiazide diuretics. In addition, use of thiazide diuretics during pregnancy has been associated with fetal or neonatal electrolyte abnormalities, jaundice, and/or thrombocytopenia.

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, of whom 233 were exposed to thiazide or related diuretics during the first trimester. An increased risk of malformations was found for thiazide diuretics. Use of thiazides after the first trimester does not seem to carry this risk. Thiazide diuretics may, however pose metabolic risks to the mother and fetus (hyponatremia, hypokalemia, thrombocytopenia, hyperglycemia), and may have a direct effect on smooth muscle, resulting in inhibition of labour.

Data from the U.S. Michigan Medicaid Birth Defects Study has revealed an association between the use of hydrochlorothiazide and congenital abnormalities. This was a retrospective study of 229,101 completed pregnancies between 1985 and 1992, of which 567 were exposed to hydrochlorothiazide at some time during the first trimester, and 1,173 were exposed to the drug at any time during pregnancy. Of the 567 pregnancies, there were 24 total and 7 cardiovascular birth defects (22 and 6 were expected, respectively). There were no observations of cleft palate, spina bifida, limb reduction, or hypospadias. The one instance of polydactyly did not achieve statistical significance. These data are consistent with an association between the use of hydrochlorothiazide and birth defects, although other factors, including underlying disease(s) of the mother are not accounted for.

Cases of neonatal thrombocytopenia associated with antepartum administration of thiazide diuretics have been reported.

AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

References

  1. Heinonen O, Shapiro S; Kaufman DW ed., Slone D "Birth Defects and Drugs in Pregnancy." Littleton, MA: Publishing Sciences Group, Inc. (1977): 297
  2. Rodriguez SU, Sanford LL, Hiller MC "Neonatal thrombocytopenia associated with ante-partum administration of thiazide drugs." N Engl J Med 270 (1964): 881-4
  3. Lindheimer MD, Katz AI "Sodiuim and diuretics in pregnancy." N Engl J Med 288 (1973): 891-4
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  5. Pharmaceutical Society of Australia "APPGuide online. Australian prescription products guide online. http://www.appco.com.au/appguide/default.asp" (2006):
  6. Cerner Multum, Inc. "Australian Product Information." O 0

The following applies to the ingredients: Duloxetine (found in Cymbalta)

This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus.

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned.

Risk summary: Observational study data have not produced clear drug-associated risks regarding adverse events or major birth defects.

Comments:
-A pregnancy exposure registry is available.
-Neonates exposed to this drug late in the third trimester may require respiratory support, tube feeding, and/or prolonged hospitalization.
-Exposed neonates should be monitored after delivery for direct toxic effects of this drug, drug discontinuation syndrome, and serotonin syndrome.
-Women who discontinued antidepressant use during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant use.

Animal studies have revealed increased perinatal toxicity and fetotoxicity at doses potentially correlated with maternal toxicity. There are no controlled data in human pregnancy.

Some neonates exposed to SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), or SSRIs (Selective Serotonin Reuptake Inhibitors) late in the third trimester had clinical findings including respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. This clinical picture is consistent with either direct toxic effect of SSRIs and SNRIs, drug discontinuation syndrome, or serotonin syndrome.

A less than 2-fold increase in postpartum hemorrhage was determined by observational data in patients exposed to the drug within 1 month before birth.

A study of women with a history of major depression who were euthymic at the beginning of pregnancy, showed women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication.

To monitor maternal-fetal outcomes of pregnant women exposed to antidepressant therapy, a National Pregnancy Registry for Antidepressants has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/

Healthcare providers are encouraged to register patients receiving Cymbalta by calling the Cymbalta Pregnancy Registry at 1-866-814-6975 or by visiting www.cymbaltapregnancyregistry.com.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

References

  1. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0

Drug and Breastfeeding Interactions

The following applies to the ingredients: Hydrochlorothiazide

Manufacturer recommendation: Use is not recommended and a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Excreted into human milk: Yes

According to LactMed this drug has been used without apparent harmful effects in the nursing infant at doses of 50 mg daily or less. Large doses may cause intense diuresis resulting in a decrease in breastmilk production.

References

  1. "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc PROD (2002):
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. United States National Library of Medicine "Toxnet. Toxicology Data Network. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT" (2013):

The following applies to the ingredients: Duloxetine (found in Cymbalta)

Use is not recommended and a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Excreted into human milk: Yes

Comments:
-Some experts state that a more thoroughly studied alternative agent (e.g., nortriptyline, paroxetine, sertraline) may be preferred while breastfeeding premature or neonates.
-The American Academy of Pediatrics classifies other antidepressants as agents for which the effect on nursing infants is unknown but may be of concern.
-Exposed infants should be monitored for developmental milestones, feeding, sedation, weight gain, especially in younger infants who are exclusively breastfed and/or when breastfed infants are exposed to multiple antipsychotropic agents.

The estimated neonatal dose is approximately 0.1% to 0.3% of the maternal dose.

References

  1. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. United States National Library of Medicine "Toxnet. Toxicology Data Network. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT" (2013):
  5. Briggs GG, Freeman RK. "Drugs in Pregnancy and Lactation." Philadelphia, PA: Wolters Kluwer Health (2015):
  6. National Library of Medicine (US) "Drugs and Lactation Database (LactMed) https://www.ncbi.nlm.nih.gov/books/NBK501922/" (2019):

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.

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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.

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