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7 Interactions found for:

trazodone and Zoloft
Interactions Summary
  • 5 Major
  • 2 Moderate
  • 0 Minor
  • trazodone
  • Zoloft

Drug Interactions

Major
Trazodone + Zoloft

The following applies to the ingredients: Trazodone and Sertraline (found in Zoloft)

MONITOR CLOSELY: Concomitant use of agents with serotonergic activity such as serotonin reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, 5-HT1 receptor agonists, ergot alkaloids, cyclobenzaprine, lithium, St. John's wort, phenylpiperidine opioids, dextromethorphan, and tryptophan may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: In general, the concomitant use of multiple serotonergic agents should be avoided if possible, or otherwise approached with caution if potential benefit is deemed to outweigh the risk. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. The potential risk for serotonin syndrome should be considered even when administering serotonergic agents sequentially, as some agents may demonstrate a prolonged elimination half-life. For example, some experts suggest a 5-week washout period following use of fluoxetine and 3 weeks following the use of vortioxetine before administering another serotonergic agent. Individual product labeling for washout periods should be consulted for current recommendations. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures.

References

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  51. Margolese HC, Chouinard G "Serotonin syndrome from addition of low-dose trazodone to nefazodone." Am J Psychiatry 157 (2000): 1022
  52. Mackay FJ, Dunn NR, Mann RD "Antidepressants and the serotonin syndrome in general practice." Br J Gen Pract 49 (1999): 871-4
  53. Smith DL, Wenegrat BG "A case report of serotonin syndrome associated with combined nefazodone and fluoxetine." J Clin Psychiatry 61 (2000): 146
  54. Rosebraugh CJ, floxkhart DA, Yasuda SU, Woosley RL "Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient." J Clin Pharmacol 41 (2001): 224-7
  55. Izzo AA, Ernst E "Interactions between herbal medicines and prescribed drugs: a systematic review." Drugs 61 (2001): 2163-75
  56. Duggal HS, Fetchko J "Serotonin syndrome and atypical antipsychotics." Am J Psychiatry 159 (2002): 672-3
  57. Wigen CL, Goetz MB "Serotonin syndrome and linezolid." Clin Infect Dis 34 (2002): 1651-2
  58. Hammerness P, Parada H, Abrams A "Linezolid: MAOI Activity and Potential Drug Interactions." Psychosomatics 43 (2002): 248-9
  59. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals (2002):
  60. Dougherty JA, Young H, Shafi T "Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine." Ann Pharmacother 36 (2002): 1647-1648
  61. Turkel SB, Nadala JG, Wincor MZ "Possible serotonin syndrome in association with 5-HT3 antagonist agents." Psychosomatics 42 (2001): 258-60
  62. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  63. Lavery S, Ravi H, McDaniel WW, Pushkin YR "Linezolid and serotonin syndrome." Psychosomatics 42 (2001): 432-4
  64. Lane R, Baldwin D "Selective serotonin reuptake inhibitor--induced serotonin syndrome: review." J Clin Psychopharmacol 17 (1997): 208-21
  65. Bernard L, Stern R, Lew D, Hoffmeyer P "Serotonin syndrome after concomitant treatment with linezolid and citalopram." Clin Infect Dis 36 (2003): 1197
  66. Dannawi M "Possible serotonin syndrome after combination of buspirone and St John's Wort." J Psychopharmacol 16 (2002): 401
  67. Tissot TA "Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use." Anesthesiology 98 (2003): 1511-1512
  68. Hachem RY, Hicks K, Huen A, Raad I "Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients." Clin Infect Dis 37 (2003): E8-E11
  69. Gillman PK "Linezolid and serotonin toxicity." Clin Infect Dis 37 (2003): 1274-5
  70. Roy S, Fortier LP "Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafexine." Can J Anaesth 50 (2003): 32-5
  71. Giese SY, Neborsky R "Serotonin syndrome: potential consequences of Meridia combined with Demerol or fentanyl." Plast Reconstr Surg 107 (2001): 293-4
  72. Jones SL, Athan E, O'Brien D "Serotonin syndrome due to co-administration of linezolid and venlafaxine." J Antimicrob Chemother 54 (2004): 289-90
  73. Tahir N "Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram." J Am Med Dir Assoc 5 (2004): 111-3
  74. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):
  75. Thomas CR, Rosenberg M, Blythe V, Meyer WJ 3rd "Serotonin syndrome and linezolid." J Am Acad Child Adolesc Psychiatry 43 (2004): 790
  76. Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20
  77. Bergeron L, Boule M, Perreault S "Serotonin toxicity associated with concomitant use of linezolid." Ann Pharmacother 39 (2005): 956-61
  78. Morales N, Vermette H "Serotonin syndrome associated with linezolid treatment after discontinuation of fluoxetine." Psychosomatics 46 (2005): 274-5
  79. Morales-Molina JA, Mateu-de Antonio J, Marin-Casino M, Grau S "Linezolid-associated serotonin syndrome: what we can learn from cases reported so far." J Antimicrob Chemother 56 (2005): 1176-8
  80. DeBellis RJ, Schaefer OP, Liquori M, Volturo GA "Linezolid-associated serotonin syndrome after concomitant treatment with citalopram and mirtazepine in a critically ill bone marrow transplant recipient." J Intensive Care Med 20 (2005): 351-3
  81. Hunter B, Kleinert MM, Osatnik J, Soria E "Serotonergic syndrome and abnormal ocular movements: worsening of rigidity by remifentanil?" Anesth Analg 102 (2006): 1589
  82. Taylor JJ, Wilson JW, Estes LL "Linezolid and serotonergic drug interactions: a retrospective survey." Clin Infect Dis 43 (2006): 180-7
  83. Strouse TB, Kerrihard TN, Forscher CA, Zakowski P "Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine." J Clin Psychopharmacol 26 (2006): 681-683
  84. Keegan MT, Brown DR, Rabinstein AA "Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs." Anesth Analg 103 (2006): 1466-8
  85. Paruchuri P, Godkar D, Anandacoomarswamy D, Sheth K, Niranjan S "Rare case of serotonin syndrome with therapeutic doses of paroxetine." Am J Ther 13 (2006): 550-552
  86. Steinberg M, Morin AK "Mild serotonin syndrome associated with concurrent linezolid and fluoxetine." Am J Health Syst Pharm 64 (2007): 59-62
  87. Packer S, Berman SA "Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid." Am J Psychiatry 164 (2007): 346-7
  88. Shapiro RE, Tepper SJ "The serotonin syndrome, triptans, and the potential for drug-drug interactions." Headache 47 (2007): 266-9
  89. Ailawadhi S, Sung KW, Carlson LA, Baer MR "Serotonin syndrome caused by interaction between citalopram and fentanyl." J Clin Pharm Ther 32 (2007): 199-202
  90. "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories (2008):
  91. Rang ST, Field J, Irving C "Serotonin toxicity caused by an interaction between fentanyl and paroxetine." Can J Anaesth 55 (2008): 521-5
  92. "Product Information. Savella (milnacipran)." Forest Pharmaceuticals (2009):
  93. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):
  94. Lee J, Franz L, Goforth HW "Serotonin syndrome in a chronic-pain patient receiving concurrent methadone, ciprofloxacin, and venlafaxine." Psychosomatics 50 (2009): 638-9
  95. "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC (2011):
  96. Mugele J, Nanagas KA, Tormoehlen LM "Serotonin Syndrome Associated With MDPV Use: A Case Report." Ann Emerg Med (2012):
  97. "Product Information. Oleptro (trazodone)." Labopharm Inc (2012):
  98. "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals (2013):
  99. "Product Information. Brintellix (vortioxetine)." Takeda Pharmaceuticals America (2013):
  100. "Product Information. Exxua (gepirone)." Mission Pharmacal Company 1 (2023):

Drug and Food Interactions

Moderate
Trazodone + Food

The following applies to the ingredients: Trazodone

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 "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):

Moderate
Zoloft + Food

The following applies to the ingredients: Sertraline (found in Zoloft)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of sertraline. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, limited clinical data suggest that consumption of grapefruit juice during treatment with sertraline may result in increased plasma concentrations of sertraline. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit. An in-vitro study demonstrated that grapefruit juice dose-dependently inhibits the conversion of sertraline to its metabolite, desmethylsertraline. In a study with eight Japanese subjects, mean plasma levels of sertraline increased by approximately 100% and maximum plasma concentrations increased by 66% after the ingestion of three 250 mL glasses of grapefruit juice per day for 5 days and administration of a single dose of sertraline 75 mg on the sixth day. In another small study with 5 patients, mean sertraline trough levels increased by 47% after taking sertraline for at least 6 weeks, then taking sertraline with 240 mL grapefruit juice daily for 1 week. The clinical significance is unknown; however, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. The possibility of significant interaction in some patients should be considered.

MANAGEMENT: Patients receiving sertraline should be 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 sertraline affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Some authorities recommend that consumption of grapefruit juice should be avoided during sertraline therapy.

References

  1. "Product Information. Zoloft (sertraline)." Roerig Division PROD (2001):
  2. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther 21 (1999): 1890-9
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Ueda N, Yoshimura R, Umene-Nakano W, et al. "Grapefruit juice alters plasma sertraline levels after single ingestion of sertraline in healthy volunteers." World J Biol Psychiatry 10(4 Pt 3) (2009): 832-5

Drug and Pregnancy Interactions

The following applies to the ingredients: Trazodone

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.
-Some experts recommend: Use with caution; use should be avoided during the first trimester of pregnancy.

US FDA pregnancy category: C

Comment: When this drug is used until delivery, newborns should be monitored for the occurrence of withdrawal symptoms.

Animal studies have revealed evidence of increased fetal resorption and congenital anomalies in adolescents. Other animal models have failed to reveal evidence of adverse effects on embryofetal development, parturition, or postnatal development when given at therapeutic doses. There are no controlled data in human pregnancy.

US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

References

  1. "Product Information. Desyrel (trazodone)." Bristol-Myers Squibb PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

The following applies to the ingredients: Sertraline (found in Zoloft)

This drug should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus, taking into account the risks of untreated depression.
-Oral concentrate and solution formulations containing alcohol: Not recommended.

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

Risk summary: Malformative risk is unlikely when given during the first trimester. There is inconclusive data on use of this drug in the third trimester to inform of a drug-related risk.

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 (e.g., respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo/hypertonia, hyperreflexia, tremor, jitteriness, irritability, constant crying).

Animal studies have failed to reveal evidence of teratogenicity; however, there was evidence of delayed ossification and effects on reproduction attributed to maternal toxicity. Decreased neonatal survival following maternal administration at exposures similar to or slightly greater than the maximum recommended human dose of 200 mg was also observed; the clinical significance is unknown. There are no controlled data in human pregnancy.

The results of several studies suggest that the use of SSRIs in the first trimester of pregnancy may be associated with an increased risk of cardiovascular and/or other congenital malformations; however, this association has not been clearly established. The association appears to be strongest for another SSRI, paroxetine.

Use of sertraline during pregnancy has been reported to cause symptoms compatible with withdrawal reactions in neonates whose mothers had taken sertraline. Neonates exposed to SSRIs and SNRIs late in the third trimester have uncommonly reported clinical findings including respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These effects have mostly occurred either at birth or within a few days of birth. These features are consistent with either a direct toxic effect of SSRIs and SNRIs, or possibly a drug discontinuation syndrome; in some cases, the clinical picture is consistent with serotonin syndrome. The results of a cohort study indicate that 30% of neonates who had prolonged exposure to SSRIs in utero experience symptoms, in a dose-response manner, of a neonatal abstinence syndrome after birth. The authors suggest that infants exposed to SSRIs should be closely monitored for a minimum of 48 hours after birth.

Epidemiological data have suggested that the use of SSRIs, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn. Data are not available for SNRIs.

One study compared 267 women exposed to an SSRI - either fluvoxamine, paroxetine, or sertraline, to 267 controls. Exposure to SSRIs was not associated with either increased risk for major malformations, higher rates of miscarriage, stillbirth, or prematurity. Mean birth weights among SSRI users were similar to controls as were the gestational ages. The study concluded that the SSRIs fluvoxamine, paroxetine, and sertraline did not appear to increase teratogenic risk when used in their recommended doses.

Animal data with sertraline have not shown an effect on fertility. Human case reports from some SSRIs have shown an effect on sperm quality that is reversible. As yet, the impact of this on human fertility has not been observed.

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/

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 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. Zoloft (sertraline)." Roerig Division PROD (2001):
  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: Trazodone

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.
-Some experts recommend: Caution is recommended.

Excreted into human milk: Yes

Comments:
-The effects in the nursing infant are unknown.
-The American Academy of Pediatrics considers this agent a drug for which the effect on nursing infants is unknown but may be of concern.

References

  1. "Product Information. Desyrel (trazodone)." Bristol-Myers Squibb PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Briggs GG, Freeman RK. "Drugs in Pregnancy and Lactation." Philadelphia, PA: Wolters Kluwer Health (2015):

The following applies to the ingredients: Sertraline (found in Zoloft)

Use is not recommended; benefit to the mother should outweigh risk to the infant.

Excreted into human milk: Yes

Comments:
-This drug has been considered one of the preferred antidepressants during breastfeeding.
-Accumulation of the drug may occur in preterm infants with impaired metabolic activity; effects similar to neonatal abstinence may rarely present in these infants.
-Mothers taking an SSRI during pregnancy and postpartum may have difficulty breastfeeding and may require additional breastfeeding support.

Benign neonatal sleep myoclonus in a 4-month-old infant and agitation in that spontaneously resolved in another infant was reported to the Australian Adverse Drug Reaction Advisory Committee and may be related to the presence of sertraline in breastmilk.

Levels of sertraline in breastmilk are reported to be low; the weakly active metabolite desmethylsertraline may be detectable in low levels. In a study of 26 breastfeeding women who were, on average, 15.8 weeks postpartum and receiving an average of 124 mg sertraline daily for at least 14 days for severe depression, complete sets of milk sample data were available for 15 mothers. Analysis of these samples led the study authors to estimate that an exclusively breastfed infant would receive an average of 0.54% of the maternal weight-adjusted dosage. Pumping and discarding milk 8 to 9 hours after the mother's dose would decrease the infant's daily dosage by 17%.

Amounts of sertraline ingested by breastfed infants are reported to be small. There was an analysis of 30 breastfed infants aged 6 to 13 weeks, of which 19 were exclusively breastfed and 11 breastfed at least half the time. Serum sertraline levels were below 1 mcg/L in 22 infants. The other 8 infants had an average serum sertraline level of 7.9 mcg/L; their mothers were taking a average of 109 mg sertraline daily, with an average serum level of 52.8 mcg/L.

The data from one study on three breast-fed infants suggested that sertraline and/or its almost inactive metabolite norsertraline may be present at very low concentrations in the plasma of breast-fed infants. No adverse effects were noted in the infants.

A pooled analysis of 53 mother-infant pairs from published and unpublished cases found that infants had an average of 2% of the sertraline plasma levels of the mothers'; three of the infants had a plasma level greater than 10% of the mothers'.

A study of fourteen mother-infant pairs reported that while mothers receiving clinical doses of sertraline experienced substantial blockade of the platelet 5-HT transporter, platelet 5-HT uptake in nursing infants of treated mothers was unaltered.

Another study of twelve breast-feeding mothers reported that both sertraline and desmethylsertraline were present in all breast milk samples. Detectable levels of sertraline were reported in three nursing infants and detectable levels of desmethylsertraline were reported in six infants.

A case study of a mother breast-feeding while receiving sertraline therapy has also been reported. The drug was found to be present in the mother's milk. However, no sertraline was detected in the infant's serum and no abnormal occurrences were noted in the development of this infant either.

References

  1. "Product Information. Zoloft (sertraline)." Roerig Division PROD (2001):
  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):

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.

Switch to: Consumer Interactions

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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