Drug Interactions between Bactrim DS and Elixophyllin KI
This report displays the potential drug interactions for the following 2 drugs:
- Bactrim DS (sulfamethoxazole/trimethoprim)
- Elixophyllin KI (potassium iodide/theophylline)
Interactions between your drugs
trimethoprim potassium iodide
Applies to: Bactrim DS (sulfamethoxazole / trimethoprim) and Elixophyllin KI (potassium iodide / theophylline)
MONITOR CLOSELY: The use of trimethoprim in combination with other potassium-sparing drugs or potassium salts may increase the risk of hyperkalemia. Trimethoprim inhibits sodium reabsorption and potassium excretion by blocking sodium channels in the renal distal tubules. Studies of patients treated with standard and high dosages of trimethoprim-sulfamethoxazole compared to similar controls treated with other antibiotics indicate that reversible increases in serum potassium are fairly common with trimethoprim use. Although generally asymptomatic, severe hyperkalemia including metabolic acidosis, paralysis, nonoliguric renal failure, and ventricular arrhythmia have been reported. Risk factors for developing hyperkalemia include use of high dosages of trimethoprim (e.g., for the treatment of MRSA skin infections or Pneumocystis jiroveci pneumonia (PCP) in AIDS patients); renal impairment or age-related decline in renal function; aldosterone or adrenal insufficiency; concomitant use of drugs that increase the risk of hyperkalemia (e.g., ACE inhibitors, angiotensin II receptor blockers, aldosterone antagonists; potassium-sparing diuretics); diets with potassium-rich foods (e.g., tomatoes, raisins, figs, baked potatoes, bananas, papayas, pears, cantaloupe, mangoes); and use of potassium salt substitutes.
MANAGEMENT: Serum potassium and sodium levels as well as renal function should be closely monitored during coadministration of trimethoprim with other potassium-sparing drugs or potassium salts, particularly in patients receiving high-dose or long-term trimethoprim treatment and in patients with renal impairment, diabetes, old age, severe or worsening heart failure, or dehydration. A dosage reduction of trimethoprim is recommended in renal dysfunction (50% reduction for CrCl between 15 and 30 mL/min). Patients should be given dietary counseling to avoid excessive intake of potassium-rich foods and salt substitutes, and advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as nausea, vomiting, weakness, listlessness, tingling of the extremities, paralysis, confusion, weak pulse, and a slow or irregular heartbeat. Trimethoprim should be discontinued if hyperkalemia occurs.
References
- "Product Information. Bactrim (sulfamethoxazole-trimethoprim)." Roche Laboratories (2022):
- Lawson DH, O'Connor PC, Jick H "Drug attributed alterations in potassium handling in congestive cardiac failure." Eur J Clin Pharmacol 23 (1982): 21-5
- Greenberg S, Reiser IW, Chou SY "Hyperkalemia with high-dose trimethoprim-sulfamethoxazole therapy." Am J Kidney Dis 22 (1993): 603-6
- Choi MJ, Fernandez PC, Patnaik A, Coupaye-Gerard B, D'Andrea D, Szerlip H, Kleyman TR "Brief report: trimethoprim-induced hyperkalemia in a patient with AIDS." N Engl J Med 328 (1993): 703-6
- Velazquez H, Perazella MA, Wright FS, Ellison DH "Renal mechanism of trimethoprim-induced hyperkalemia." Ann Intern Med 119 (1993): 296-301
- Smith GW, Cohen SB "Hyperkalaemia and non-oliguric renal failure associated with trimethoprim." Br Med J 308 (1994): 454
- Modest GA, Price B, Mascoli N "Hyperkalemia in elderly patients receiving standard doses of trimethoprim-sulfamethoxazole." Ann Intern Med 120 (1994): 437
- Pennypacker LC, Mintzer J, Pitner J "Hyperkalemia in elderly patients receiving standard doses of trimethoprim-sulfamethoxazole." Ann Intern Med 120 (1994): 437
- Canaday DH, Johnson JR "Hyperkalemia in elderly patients receiving standard doses of trimethoprim-sulfamethoxazole." Ann Intern Med 120 (1994): 438
- Lawson DH "Adverse reactions to potassium chloride." Q J Med 43 (1974): 433-40
- Hsu I, Wordell CJ "Hyperkalemia and high-dose trimethoprim/sulfamethoxazole." Ann Pharmacother 29 (1995): 427-9
- Marinella MA "Reversible hyperkalemia associated with trimethoprim-sulfamethoxazole." Am J Med Sci 310 (1995): 115-7
- Mihm LB, Rathbun RC, Resmantargoff BH "Hyperkalemia associated with high-dose trimethoprim-sulfamethoxazole in a patient with the acquired immunodeficiency syndrome." Pharmacotherapy 15 (1995): 793-7
- Alappan R, Perazella MA, Buller GK "Hyperkalemia in hospitalized patients treated with trimethoprim-sulfamethoxazole." Ann Intern Med 124 (1996): 316-20
- Witt JM, Koo JM, Danielson BD "Effect of standard-dose trimethoprim/sulfamethoxazole on the serum potassium concentration in elderly men." Ann Pharmacother 30 (1996): 347-50
- Thomas RJ "Severe hyperkalemia with trimethoprim-quinapril." Ann Pharmacother 30 (1996): 413-4
- Eiam-Ong S, Kurtzman NA, Sabatini S "Studies on the mechanism of trimethoprim-induced hyperkalemia." Kidney Int 49 (1996): 1372-8
- Perazella MA, Mahnensmith RL "Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication regardless of dose." Clin Nephrol 46 (1996): 187-92
- Bugge JF "Severe hyperkalaemia induced by trimethoprim in combination with an angiotensin-converting enzyme inhibitor in a patient with transplanted lungs." J Intern Med 240 (1996): 249-51
- Perazella MA, Alappan R, Buller GK "Hyperkalemia and trimethoprim-sulfamethoxazole." Ann Intern Med 125 (1996): 1015
- Fouche R, Bernardin G, Roger PM, Corcelle P, Simler JM, Mattei M "Hyperkaliemia in a patient given high-dose trimethoprim-sulfamethoxazole." Presse Med 25 (1996): 2044
- Marinella MA "Severe hyperkalemia associated with trimethoprim-sulfamethoxazole and spironolactone." Infect Dis Clin Pract 6 (1997): 256-8
- Perlmutter EP, Sweeney D, Herskovits G, Kleiner M "Case report: severe hyperkalemia in a geriatric patient receiving standard doses of trimethoprim-sulfamethoxazole." Am J Med Sci 311 (1996): 84-5
- Marinella MA "Trimethoprim-sulfamethoxazole associated with hyperkalemia." West J Med 167 (1997): 356-8
- Koc M, Bihorac A, Ozener CI, Kantarci G, Akoglu E "Severe hyperkalemia in two renal transplant recipients treated with standard dose of trimethoprim-sulfamethoxazole." Am J Kidney Dis 36 (2000): u59-64
- Martin J, Mourton S, Nicholls G "Severe hyperkalaemia with prescription of potassium-retaining agents in an elderly patient." N Z Med J 116 (2003): U542
- Marcy TR, Ripley TL "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm 63 (2006): 49-58
- "Prevent-ERR: sulfamethoxazole and trimethoprim-induced hyperkalemia." ISMP Medication Safety Alert! 13(Dec 4) (2008): 3
- Noto H, Kaneko Y, Takano T, Kurokawa K "Severe hyponatremia and hyperkalemia induced by trimethoprim-sulfamethoxazole in patients with Pneumocystis carinii pneumonia." Intern Med 34 (1995): 96-9
- Lin SH, Kuo AA, Yu FC, Lin YF "Reversible voltage-dependent distal renal tubular acidosis in a patient receiving standaard doses of trimethoprim-sulphamethoxazole." Nephrol Dial Transplant 12 (1997): 1031-33
- Mori H, Kuroda Y, Imamura S, et al. "Hyponatremia and/or hyperkalemia in patients treated with the standard dose of trimethoprim-sulfamethoxazole." Intern Med 42 (2003): 665-9
- Perazella MA "Drug-induced hyperkalemia: old culprits and new offenders." Am J Med 109 (2000): 307-14
- Perazella MA, Mahnensmith RL "Hyperkalemia in the elderly: drugs exacerbate impaired potassium homeostasis." J Gen Intern Med 12 (1997): 646-56
- Antoniou T, Gomes T, Juurlink DN, Loutfy MR, Glazier RH, Mamdani MM "Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study." Arch Intern Med 170 (2010): 1045-9
- Lee SW, Park SW, Kang JM "Intraoperative hyperkalemia induced by administration of trimethoprim-sulfamethoxazole in a patient receiving angiotensin receptor blockers." J Clin Anesth 26 (2014): 427-8
Drug and food interactions
theophylline food
Applies to: Elixophyllin KI (potassium iodide / 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
- Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
- Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8
- Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67
sulfamethoxazole food
Applies to: Bactrim DS (sulfamethoxazole / trimethoprim)
MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.
MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.
References
- Heelon MW, White M "Disulfiram-cotrimoxazole reaction." Pharmacotherapy 18 (1998): 869-70
- Mergenhagen KA, Wattengel BA, Skelly MK, Clark CM, Russo TA "Fact versus fiction: a review of the evidence behind alcohol and antibiotic interactions." Antimicrob Agents Chemother 64 (2020): e02167-19
theophylline food
Applies to: Elixophyllin KI (potassium iodide / 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
- Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
- Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8
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.
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
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