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Drug Interactions between acetaminophen / aspirin / phenylpropanolamine and Zoloft

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

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Interactions between your drugs

Major

phenylpropanolamine sertraline

Applies to: acetaminophen / aspirin / phenylpropanolamine and Zoloft (sertraline)

GENERALLY AVOID: Several case reports suggest that serotonin reuptake inhibitors may potentiate the pharmacologic response to sympathomimetic agents. The exact mechanism of interaction is unclear. In one case report, a patient experienced jitteriness, racing thoughts, stomach cramps, dry eyes, palpitations, tremors, and restlessness following a single dose of phentermine ingested approximately a week after she had discontinued fluoxetine. Because of the long half-life of fluoxetine and its metabolite, an interaction with fluoxetine is possible. Similar toxic reactions have been reported when fluoxetine was used concomitantly with amphetamine or phenylpropanolamine. Additionally, some sympathomimetic agents such as amphetamines may possess serotonergic activity and should generally not be administered with serotonin reuptake inhibitors because of the additive 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. The interaction was suspected in a patient treated with dexamphetamine who developed symptoms consistent with the serotonin syndrome approximately 2 weeks after the addition of venlafaxine. The medications were discontinued and the patient was given cyproheptadine for suspected serotonin syndrome, whereupon symptoms promptly resolved. A second episode occurred when dexamphetamine was subsequently resumed and citalopram added. The patient improved following cessation of citalopram on his own, and residual symptoms were successfully treated with cyproheptadine.

MANAGEMENT: In general, amphetamines and other sympathomimetic appetite suppressants should not be combined with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Close monitoring for enhanced sympathomimetic effects and possible serotonin syndrome is recommended if these agents must be used together. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucinations, 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.

References

  1. Walters AM "Sympathomimetic-fluoxetine interaction." J Am Acad Child Adolesc Psychiatry 31 (1992): 565-6
  2. Barrett J, Meehan O, Fahy T "SSRI and sympathomimetic interaction." Br J Psychiatry 168 (1996): 253
  3. Bostwick JM, Brown TM "A toxic reaction from combining fluoxetine and phentermine." J Clin Psychopharmacol 16 (1996): 189-90
  4. Braunwald E, Hauser SL, Kasper DL, Fauci AS, Isselbacher KJ, Longo DL, Martin JB, eds., Wilson JD "Harrison's Principles of Internal Medicine." New York, NY: McGraw-Hill Health Professionals Division (1998):
  5. Prior FH, Isbister GK, Dawson AH, Whyte IM "Serotonin toxicity with therapeutic doses of dexamphetamine and venlafaxine." Med J Aust 176 (2002): 240-1
  6. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
View all 6 references

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Moderate

aspirin sertraline

Applies to: acetaminophen / aspirin / phenylpropanolamine and Zoloft (sertraline)

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

Major

acetaminophen food

Applies to: acetaminophen / aspirin / phenylpropanolamine

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

References

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med 145 (1985): 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
  4. Thummel KE, Slattery JT, Nelson SD "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther 245 (1988): 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA 244 (1980): 251-3
  6. Kartsonis A, Reddy KR, Schiff ER "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med 105 (1986): 138-9
  7. Prescott LF, Critchley JA "Drug interactions affecting analgesic toxicity." Am J Med 75 (1983): 113-6
  8. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical PROD (2002):
  9. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50
  10. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  11. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  12. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73
View all 12 references

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Moderate

phenylpropanolamine food

Applies to: acetaminophen / aspirin / phenylpropanolamine

GENERALLY AVOID: Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

MANAGEMENT: Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease. Patients should be counselled 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. Mendelson J, Jones RT, Upton R, Jacob P 3rd "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther 57 (1995): 559-68
  2. "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn PROD (2001):
  3. "Product Information. Suprenza (phentermine)." Akrimax Pharmaceuticals (2012):

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Moderate

sertraline food

Applies to: Zoloft (sertraline)

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
View all 4 references

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Moderate

aspirin food

Applies to: acetaminophen / aspirin / phenylpropanolamine

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

phenylpropanolamine food

Applies to: acetaminophen / aspirin / phenylpropanolamine

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
  3. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  4. "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
  5. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  6. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  7. "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
View all 7 references

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Minor

aspirin food

Applies to: acetaminophen / aspirin / phenylpropanolamine

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.


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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.