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Drug Interactions between dexamethasone / ketorolac / moxifloxacin and ibuprofen / oxycodone

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

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Interactions between your drugs

Major

ibuprofen ketorolac

Applies to: ibuprofen / oxycodone and dexamethasone / ketorolac / moxifloxacin

CONTRAINDICATED: The use of ketorolac in combination with other nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of serious adverse effects such as renal failure and gastrointestinal toxicity including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, or intestines.

MANAGEMENT: Concurrent use of ketorolac with other NSAIDs or aspirin is considered contraindicated.

References

  1. (2002) "Product Information. Toradol (ketorolac)." Roche Laboratories

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Major

dexAMETHasone oxyCODONE

Applies to: dexamethasone / ketorolac / moxifloxacin and ibuprofen / oxycodone

MONITOR CLOSELY: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of opioids that are primarily metabolized by the isoenzyme such as butorphanol, fentanyl, hydrocodone, and oxycodone. Reduced efficacy or withdrawal symptoms may occur in patients maintained on their narcotic pain regimen following the addition of a CYP450 3A4 inducer. Conversely, discontinuation of the inducer may increase opioid plasma concentrations and potentiate the risk of overdose and fatal respiratory depression.

MANAGEMENT: Pharmacologic response to the opioid should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the opioid dosage adjusted as necessary.

References

  1. (2001) "Product Information. Mycobutin (rifabutin)." Pharmacia and Upjohn
  2. (2001) "Product Information. Rifadin (rifampin)." Hoechst Marion Roussel
  3. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  4. (2001) "Product Information. OxyContin (oxycodone)." Purdue Frederick Company
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  6. (2006) "Product Information. Ionsys (fentanyl)." Ortho McNeil Pharmaceutical
  7. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  8. Cerner Multum, Inc. "Australian Product Information."
  9. (2013) "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc
  10. (2017) "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation
View all 10 references

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Major

dexAMETHasone moxifloxacin

Applies to: dexamethasone / ketorolac / moxifloxacin and dexamethasone / ketorolac / moxifloxacin

MONITOR CLOSELY: Concomitant administration of corticosteroids may potentiate the risk of tendinitis and tendon rupture associated with fluoroquinolone treatment. The mechanism is unknown. Tendinitis and tendon rupture have most frequently involved the Achilles tendon, although cases involving the rotator cuff (the shoulder), the hand, the biceps, and the thumb have also been reported. Some have required surgical repair or resulted in prolonged disability. Tendon rupture can occur during or up to several months after completion of fluoroquinolone therapy.

MANAGEMENT: Caution is recommended if fluoroquinolones are prescribed in combination with corticosteroids, particularly in patients with other concomitant risk factors (e.g., age over 60 years; recipient of kidney, heart, and/or lung transplant). Patients should be advised to stop taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact their physician if they experience pain, swelling, or inflammation of a tendon. In general, fluoroquinolones should only be used to treat conditions that are proven or strongly suspected to be caused by bacteria and only if the benefits outweigh the risks.

References

  1. (2002) "Product Information. Cipro (ciprofloxacin)." Bayer
  2. (2001) "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical
  3. (2001) "Product Information. Avelox (moxifloxacin)." Bayer
  4. Khaliq Y, Zhanel GG (2003) "Fluoroquinolone-Associated Tendinopathy: A Critical Review of the Literature." Clin Infect Dis, 36, p. 1404-1410
  5. van der Linden PD, Sturkenboom MC, Herings RM, Leufkens HM, Rowlands S, Stricker BH (2003) "Increased risk of achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids." Arch Intern Med, 163, p. 1801-7
  6. FDA. U.S. Food and Drug Administration (2008) Information for Healthcare Professionals. Fluoroquinolone Antimicrobial Drugs. FDA Alert [7/8/2008]. http://www.fda.gov/cder/drug/InfoSheets/HCP/fluoroquinolonesHCP.htm
  7. (2017) "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc.
View all 7 references

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Moderate

ibuprofen dexAMETHasone

Applies to: ibuprofen / oxycodone and dexamethasone / ketorolac / moxifloxacin

MONITOR: The combined use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the potential for serious gastrointestinal (GI) toxicity, including inflammation, bleeding, ulceration, and perforation. In a large, case-control study of elderly patients, those who used corticosteroids and NSAIDs concurrently had an estimated relative risk (RR) for peptic ulcer disease and GI hemorrhage of 14.6 compared to those who used neither. Corticosteroid use was associated with a doubling of the risk (estimated RR = 2.0), but the risk was confined to those who also used NSAIDs. It is possible that both categories of agents are ulcerogenic and have additive effects on the GI mucosa during coadministration. Some investigators have also suggested that the primary effect of corticosteroids in this interaction is to delay healing of erosions caused by NSAIDs rather than cause de novo ulcerations.

MANAGEMENT: Caution is advised if corticosteroids and NSAIDs are used together, especially in patients with a prior history of peptic ulcer disease or GI bleeding and in elderly and debilitated patients. During concomitant therapy, patients should be advised to take the medications with food and to immediately report signs and symptoms of GI ulceration and bleeding such as severe abdominal pain, dizziness, lightheadedness, and the appearance of black, tarry stools. The selective use of prophylactic anti-ulcer therapy (e.g., antacids, H2-antagonists) may be considered.

References

  1. Stewart JT, Pennington CR, Pringle R (1985) "Anti-inflammatory drugs and bowel perforations and haemorrhage." Br Med J, 290, p. 787-8
  2. Thomas TP (1984) "The complications of systemic corticosteroid therapy in the elderly." Gerontology, 30, p. 60-5
  3. Messer J, Reitman D, Sacks HS, et al. (1983) "Association of adrenocorticosteroid therapy and peptic-ulcer disease." N Engl J Med, 309, p. 21-4
  4. ReMine SG, McIlrath DC (1980) "Bowel perforation in steroid-treated patients." Ann Surg, 192, p. 581-6
  5. Levy M, Miller DR, Kaufman DW, Siskind V, Schwingl P, Rosenberg L, Strom B, Shapiro S (1988) "Major upper gastrointestinal tract bleeding. Relation to the use of aspirin and other nonnarcotic analgesics." Arch Intern Med, 148, p. 281-5
  6. Kaufman DW, Kelly JP, Sheehan JE, Laszlo A, Wiholm BE, Alfredsson L, Koff RS, Shapiro S (1993) "Nonsteroidal anti-inflammatory drug use in relation to major upper gastrointestinal bleeding." Clin Pharmacol Ther, 53, p. 485-94
  7. Wilcox CM, Shalek KA, Cotsonis G (1994) "Striking prevalence of over-the-counter nonsteroidal anti- inflammatory drug use in patients with upper gastrointestinal hemorrhage." Arch Intern Med, 154, p. 42-6
  8. Cantu TG, Lipani JA (1995) "Gastrointestinal ulceration with NSAIDs." Am J Med, 99, p. 440-1
  9. Sacanella E, Munoz F, Cardellach F, Estruch R, Miro O, Urbanomarquez A (1996) "Massive haemorrhage due to colitis secondary to nonsteroidal anti-inflammatory drugs." Postgrad Med J, 72, p. 57-8
  10. Buchman AL, Schwartz MR (1996) "Colonic ulceration associated with the systemic use of nonsteroidal antiinflammatory medication." J Clin Gastroenterol, 22, p. 224-6
  11. Piper JM, Ray WA, Daugherty JR, Griffin MR (1991) "Corticosteroid use and peptic ulcer disease: role of nonsteroidal ani-inflammatory drugs." Ann Intern Med, 114, p. 735-40
View all 11 references

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Moderate

dexAMETHasone ketorolac

Applies to: dexamethasone / ketorolac / moxifloxacin and dexamethasone / ketorolac / moxifloxacin

MONITOR: The combined use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the potential for serious gastrointestinal (GI) toxicity, including inflammation, bleeding, ulceration, and perforation. In a large, case-control study of elderly patients, those who used corticosteroids and NSAIDs concurrently had an estimated relative risk (RR) for peptic ulcer disease and GI hemorrhage of 14.6 compared to those who used neither. Corticosteroid use was associated with a doubling of the risk (estimated RR = 2.0), but the risk was confined to those who also used NSAIDs. It is possible that both categories of agents are ulcerogenic and have additive effects on the GI mucosa during coadministration. Some investigators have also suggested that the primary effect of corticosteroids in this interaction is to delay healing of erosions caused by NSAIDs rather than cause de novo ulcerations.

MANAGEMENT: Caution is advised if corticosteroids and NSAIDs are used together, especially in patients with a prior history of peptic ulcer disease or GI bleeding and in elderly and debilitated patients. During concomitant therapy, patients should be advised to take the medications with food and to immediately report signs and symptoms of GI ulceration and bleeding such as severe abdominal pain, dizziness, lightheadedness, and the appearance of black, tarry stools. The selective use of prophylactic anti-ulcer therapy (e.g., antacids, H2-antagonists) may be considered.

References

  1. Stewart JT, Pennington CR, Pringle R (1985) "Anti-inflammatory drugs and bowel perforations and haemorrhage." Br Med J, 290, p. 787-8
  2. Thomas TP (1984) "The complications of systemic corticosteroid therapy in the elderly." Gerontology, 30, p. 60-5
  3. Messer J, Reitman D, Sacks HS, et al. (1983) "Association of adrenocorticosteroid therapy and peptic-ulcer disease." N Engl J Med, 309, p. 21-4
  4. ReMine SG, McIlrath DC (1980) "Bowel perforation in steroid-treated patients." Ann Surg, 192, p. 581-6
  5. Levy M, Miller DR, Kaufman DW, Siskind V, Schwingl P, Rosenberg L, Strom B, Shapiro S (1988) "Major upper gastrointestinal tract bleeding. Relation to the use of aspirin and other nonnarcotic analgesics." Arch Intern Med, 148, p. 281-5
  6. Kaufman DW, Kelly JP, Sheehan JE, Laszlo A, Wiholm BE, Alfredsson L, Koff RS, Shapiro S (1993) "Nonsteroidal anti-inflammatory drug use in relation to major upper gastrointestinal bleeding." Clin Pharmacol Ther, 53, p. 485-94
  7. Wilcox CM, Shalek KA, Cotsonis G (1994) "Striking prevalence of over-the-counter nonsteroidal anti- inflammatory drug use in patients with upper gastrointestinal hemorrhage." Arch Intern Med, 154, p. 42-6
  8. Cantu TG, Lipani JA (1995) "Gastrointestinal ulceration with NSAIDs." Am J Med, 99, p. 440-1
  9. Sacanella E, Munoz F, Cardellach F, Estruch R, Miro O, Urbanomarquez A (1996) "Massive haemorrhage due to colitis secondary to nonsteroidal anti-inflammatory drugs." Postgrad Med J, 72, p. 57-8
  10. Buchman AL, Schwartz MR (1996) "Colonic ulceration associated with the systemic use of nonsteroidal antiinflammatory medication." J Clin Gastroenterol, 22, p. 224-6
  11. Piper JM, Ray WA, Daugherty JR, Griffin MR (1991) "Corticosteroid use and peptic ulcer disease: role of nonsteroidal ani-inflammatory drugs." Ann Intern Med, 114, p. 735-40
View all 11 references

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Moderate

ibuprofen moxifloxacin

Applies to: ibuprofen / oxycodone and dexamethasone / ketorolac / moxifloxacin

MONITOR: Coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) may potentiate the risk of central nervous system toxicity sometimes associated with fluoroquinolone use. The interaction has been reported most often with enoxacin. It may occur with other fluoroquinolones as well, but is poorly documented. The exact mechanism of interaction is unknown. Some investigators suggest that the piperazine ring of fluoroquinolones may inhibit the binding of gamma-aminobutyric acid (GABA) to brain receptors and that NSAIDs may synergistically add to this effect. Patients with a history of seizures may be at greater risk.

MANAGEMENT: Clinical monitoring for signs of CNS stimulation such as tremors, involuntary muscle movements, hallucinations, or seizures is recommended if fluoroquinolone antibiotics are prescribed in combination with NSAIDs.

References

  1. Ball P (1986) "Ciprofloxacin: an overview of adverse experiences." J Antimicrob Chemother, 18, p. 187-93
  2. Hooper DC, Wolfson JS (1985) "The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans." Antimicrob Agents Chemother, 28, p. 716-21
  3. (2002) "Product Information. Cipro (ciprofloxacin)." Bayer
  4. (2002) "Product Information. Penetrex (enoxacin)." Rhone Poulenc Rorer
  5. (2001) "Product Information. Floxin (ofloxacin)." Ortho McNeil Pharmaceutical
  6. Domagala JM (1994) "Structure-activity and structure-side-effect relationships for the quinolone antibacterials." J Antimicrob Chemother, 33, p. 685-706
  7. (2001) "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical
  8. (2001) "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome
  9. Davey PG (1988) "Overview of drug interactions with the quinolones." J Antimicrob Chemother, 22(suppl c), p. 97-107
  10. Ball P, Tillotson G (1996) "Tolerability of fluoroquinolone antibiotics: past, present and future." Drug Saf, 13, p. 343-8
  11. (2001) "Product Information. Avelox (moxifloxacin)." Bayer
  12. (2001) "Product Information. Tequin (gatifloxacin)." Bristol-Myers Squibb
  13. (2003) "Product Information. Factive (gemifloxacin)." *GeneSoft Inc
  14. Segev S. Rehavi M, Rubinstein E (1988) "Quinolones, theophylline, and diclofenac interactions with the gamma-aminobutyric acid receptor." Antimicrob Agents Chemother, 32, p. 1624-6
View all 14 references

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Moderate

ketorolac moxifloxacin

Applies to: dexamethasone / ketorolac / moxifloxacin and dexamethasone / ketorolac / moxifloxacin

MONITOR: Coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) may potentiate the risk of central nervous system toxicity sometimes associated with fluoroquinolone use. The interaction has been reported most often with enoxacin. It may occur with other fluoroquinolones as well, but is poorly documented. The exact mechanism of interaction is unknown. Some investigators suggest that the piperazine ring of fluoroquinolones may inhibit the binding of gamma-aminobutyric acid (GABA) to brain receptors and that NSAIDs may synergistically add to this effect. Patients with a history of seizures may be at greater risk.

MANAGEMENT: Clinical monitoring for signs of CNS stimulation such as tremors, involuntary muscle movements, hallucinations, or seizures is recommended if fluoroquinolone antibiotics are prescribed in combination with NSAIDs.

References

  1. Ball P (1986) "Ciprofloxacin: an overview of adverse experiences." J Antimicrob Chemother, 18, p. 187-93
  2. Hooper DC, Wolfson JS (1985) "The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans." Antimicrob Agents Chemother, 28, p. 716-21
  3. (2002) "Product Information. Cipro (ciprofloxacin)." Bayer
  4. (2002) "Product Information. Penetrex (enoxacin)." Rhone Poulenc Rorer
  5. (2001) "Product Information. Floxin (ofloxacin)." Ortho McNeil Pharmaceutical
  6. Domagala JM (1994) "Structure-activity and structure-side-effect relationships for the quinolone antibacterials." J Antimicrob Chemother, 33, p. 685-706
  7. (2001) "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical
  8. (2001) "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome
  9. Davey PG (1988) "Overview of drug interactions with the quinolones." J Antimicrob Chemother, 22(suppl c), p. 97-107
  10. Ball P, Tillotson G (1996) "Tolerability of fluoroquinolone antibiotics: past, present and future." Drug Saf, 13, p. 343-8
  11. (2001) "Product Information. Avelox (moxifloxacin)." Bayer
  12. (2001) "Product Information. Tequin (gatifloxacin)." Bristol-Myers Squibb
  13. (2003) "Product Information. Factive (gemifloxacin)." *GeneSoft Inc
  14. Segev S. Rehavi M, Rubinstein E (1988) "Quinolones, theophylline, and diclofenac interactions with the gamma-aminobutyric acid receptor." Antimicrob Agents Chemother, 32, p. 1624-6
View all 14 references

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Drug and food interactions

Major

oxyCODONE food

Applies to: ibuprofen / oxycodone

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including oxycodone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of oxycodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of oxycodone by certain compounds present in grapefruit, resulting in decreased formation of metabolites noroxycodone and noroxymorphone and increased formation of oxymorphone due to a presumed shifting of oxycodone metabolism towards the CYP450 2D6-mediated route. In 12 healthy, nonsmoking volunteers, administration of a single 10 mg oral dose of oxycodone hydrochloride on day 4 of a grapefruit juice treatment phase (200 mL three times a day for 5 days) increased mean oxycodone peak plasma concentration (Cmax), systemic exposure (AUC) and half-life by 48%, 67% and 17% (from 3.5 to 4.1 hours), respectively, compared to administration during an equivalent water treatment phase. Grapefruit juice also decreased the metabolite-to-parent AUC ratio of noroxycodone by 44% and that of noroxymorphone by 45%. In addition, oxymorphone Cmax and AUC increased by 32% and 56%, but the metabolite-to-parent AUC ratio remained unchanged. Pharmacodynamic changes were modest and only self-reported performance was significantly impaired after grapefruit juice. Analgesic effects were not affected.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with oxycodone. Any history of alcohol or illicit drug use should be considered when prescribing oxycodone, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with oxycodone may also want to avoid or limit the consumption of grapefruit and grapefruit juice.

References

  1. Nieminen TH, Hagelberg NM, Saari TI, et al. (2010) "Grapefruit juice enhances the exposure to oral oxycodone." Basic Clin Pharmacol Toxicol, 107, p. 782-8

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Moderate

ibuprofen food

Applies to: ibuprofen / oxycodone

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. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

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Moderate

ketorolac food

Applies to: dexamethasone / ketorolac / moxifloxacin

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. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Nonsteroidal anti-inflammatories

Therapeutic duplication

The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category:

  • dexamethasone/ketorolac/moxifloxacin
  • ibuprofen/oxycodone

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.


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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.