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Drug Interactions between dexamethasone / ketorolac / moxifloxacin and theophylline

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

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Interactions between your drugs

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 (7)
  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.
Moderate

theophylline dexAMETHasone

Applies to: theophylline and dexamethasone / ketorolac / moxifloxacin

MONITOR: The concomitant use of theophylline and corticosteroids may theoretically increase the risk of hypokalemia due to additive potassium-lowering effects. Additionally, theophylline serum concentrations may be altered. The mechanism is unknown and data have been limited and conflicting; increased, decreased, and unchanged theophylline levels have all been reported.

MANAGEMENT: Monitoring for altered efficacy and safety of theophylline and altered serum potassium and theophylline concentrations is advisable when these drugs are coadministered. Patients should be advised to notify their physician if they experience signs of hypokalemia (e.g., weakness, lethargy, and muscle pains or cramps), worsening respiratory symptoms, or signs of theophylline toxicity (e.g., nausea, vomiting, diarrhea, headache, restlessness, insomnia, or irregular heartbeat).

References (6)
  1. Fergusson RJ, Scott CM, Rafferty P, Gaddie J (1987) "Effect of prednisolone on theophylline pharmacokinetics in patients with chronic airflow obstruction." Thorax, 42, p. 195-8
  2. Anderson JL, Ayres JW, Hall CA (1984) "Potential pharmacokinetic interaction between theophylline and prednisone." Clin Pharm, 3, p. 187-8
  3. Buchanan N, Hurwitz S, Butler P (1979) "Asthma - a possible interaction between hydrocortisone and theophylline." S Afr Med J, 56, p. 1147-8
  4. Elvey SM, Saccar CL, Rocci ML, Mansmann HC, Martynec DM, Kester MB (1986) "The effect of corticosteroids on theophylline metabolim in asthmatic children." Ann Allergy, 56, p. 520
  5. Tatsis G, Orphanidou D, Douratsos D, et al. (1991) "The effect of steroids on theophylline absorption." J Int Med Res, 19, p. 326-9
  6. Leavengood DC, Bunker-Soler AL, Nelson HS (1983) "The effect of corticosteroids on theophylline metabolism." Ann Allergy, 50, p. 249-51
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 (11)
  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
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 (14)
  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

Drug and food interactions

Moderate

theophylline food

Applies to: theophylline

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

ADJUST DOSING INTERVAL: Administration of theophylline with continuous enteral nutrition may reduce the serum levels or the rate of absorption of theophylline. The mechanism has not been reported. In one case, theophylline levels decreased by 53% in a patient receiving continuous nasogastric tube feedings and occurred with both theophylline tablet and liquid formulations, but not with intravenous aminophylline.

MANAGEMENT: When administered to patients receiving continuous enteral nutrition , some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of theophylline is given; rapid-release formulations are preferable, and theophylline levels should be monitored.

References (3)
  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
  3. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67
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)
  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn
Moderate

theophylline food

Applies to: theophylline

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

References (2)
  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
Moderate

theophylline food

Applies to: theophylline

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

References (4)
  1. (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
  2. jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
  3. Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
  4. Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38

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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