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Drug Interactions between eplerenone and Septra IV

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

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Major

trimethoprim eplerenone

Applies to: Septra IV (sulfamethoxazole / trimethoprim) and eplerenone

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

  1. (2022) "Product Information. Bactrim (sulfamethoxazole-trimethoprim)." Roche Laboratories
  2. Lawson DH, O'Connor PC, Jick H (1982) "Drug attributed alterations in potassium handling in congestive cardiac failure." Eur J Clin Pharmacol, 23, p. 21-5
  3. Greenberg S, Reiser IW, Chou SY (1993) "Hyperkalemia with high-dose trimethoprim-sulfamethoxazole therapy." Am J Kidney Dis, 22, p. 603-6
  4. Choi MJ, Fernandez PC, Patnaik A, Coupaye-Gerard B, D'Andrea D, Szerlip H, Kleyman TR (1993) "Brief report: trimethoprim-induced hyperkalemia in a patient with AIDS." N Engl J Med, 328, p. 703-6
  5. Velazquez H, Perazella MA, Wright FS, Ellison DH (1993) "Renal mechanism of trimethoprim-induced hyperkalemia." Ann Intern Med, 119, p. 296-301
  6. Smith GW, Cohen SB (1994) "Hyperkalaemia and non-oliguric renal failure associated with trimethoprim." Br Med J, 308, p. 454
  7. Modest GA, Price B, Mascoli N (1994) "Hyperkalemia in elderly patients receiving standard doses of trimethoprim-sulfamethoxazole." Ann Intern Med, 120, p. 437
  8. Pennypacker LC, Mintzer J, Pitner J (1994) "Hyperkalemia in elderly patients receiving standard doses of trimethoprim-sulfamethoxazole." Ann Intern Med, 120, p. 437
  9. Canaday DH, Johnson JR (1994) "Hyperkalemia in elderly patients receiving standard doses of trimethoprim-sulfamethoxazole." Ann Intern Med, 120, p. 438
  10. Lawson DH (1974) "Adverse reactions to potassium chloride." Q J Med, 43, p. 433-40
  11. Hsu I, Wordell CJ (1995) "Hyperkalemia and high-dose trimethoprim/sulfamethoxazole." Ann Pharmacother, 29, p. 427-9
  12. Marinella MA (1995) "Reversible hyperkalemia associated with trimethoprim-sulfamethoxazole." Am J Med Sci, 310, p. 115-7
  13. Mihm LB, Rathbun RC, Resmantargoff BH (1995) "Hyperkalemia associated with high-dose trimethoprim-sulfamethoxazole in a patient with the acquired immunodeficiency syndrome." Pharmacotherapy, 15, p. 793-7
  14. Alappan R, Perazella MA, Buller GK (1996) "Hyperkalemia in hospitalized patients treated with trimethoprim-sulfamethoxazole." Ann Intern Med, 124, p. 316-20
  15. Witt JM, Koo JM, Danielson BD (1996) "Effect of standard-dose trimethoprim/sulfamethoxazole on the serum potassium concentration in elderly men." Ann Pharmacother, 30, p. 347-50
  16. Thomas RJ (1996) "Severe hyperkalemia with trimethoprim-quinapril." Ann Pharmacother, 30, p. 413-4
  17. Eiam-Ong S, Kurtzman NA, Sabatini S (1996) "Studies on the mechanism of trimethoprim-induced hyperkalemia." Kidney Int, 49, p. 1372-8
  18. Perazella MA, Mahnensmith RL (1996) "Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication regardless of dose." Clin Nephrol, 46, p. 187-92
  19. Bugge JF (1996) "Severe hyperkalaemia induced by trimethoprim in combination with an angiotensin-converting enzyme inhibitor in a patient with transplanted lungs." J Intern Med, 240, p. 249-51
  20. Perazella MA, Alappan R, Buller GK (1996) "Hyperkalemia and trimethoprim-sulfamethoxazole." Ann Intern Med, 125, p. 1015
  21. Fouche R, Bernardin G, Roger PM, Corcelle P, Simler JM, Mattei M (1996) "Hyperkaliemia in a patient given high-dose trimethoprim-sulfamethoxazole." Presse Med, 25, p. 2044
  22. Marinella MA (1997) "Severe hyperkalemia associated with trimethoprim-sulfamethoxazole and spironolactone." Infect Dis Clin Pract, 6, p. 256-8
  23. Perlmutter EP, Sweeney D, Herskovits G, Kleiner M (1996) "Case report: severe hyperkalemia in a geriatric patient receiving standard doses of trimethoprim-sulfamethoxazole." Am J Med Sci, 311, p. 84-5
  24. Marinella MA (1997) "Trimethoprim-sulfamethoxazole associated with hyperkalemia." West J Med, 167, p. 356-8
  25. Koc M, Bihorac A, Ozener CI, Kantarci G, Akoglu E (2000) "Severe hyperkalemia in two renal transplant recipients treated with standard dose of trimethoprim-sulfamethoxazole." Am J Kidney Dis, 36, u59-64
  26. Martin J, Mourton S, Nicholls G (2003) "Severe hyperkalaemia with prescription of potassium-retaining agents in an elderly patient." N Z Med J, 116, U542
  27. Marcy TR, Ripley TL (2006) "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm, 63, p. 49-58
  28. (2008) "Prevent-ERR: sulfamethoxazole and trimethoprim-induced hyperkalemia." ISMP Medication Safety Alert!, 13(Dec 4), p. 3
  29. Noto H, Kaneko Y, Takano T, Kurokawa K (1995) "Severe hyponatremia and hyperkalemia induced by trimethoprim-sulfamethoxazole in patients with Pneumocystis carinii pneumonia." Intern Med, 34, p. 96-9
  30. Lin SH, Kuo AA, Yu FC, Lin YF (1997) "Reversible voltage-dependent distal renal tubular acidosis in a patient receiving standaard doses of trimethoprim-sulphamethoxazole." Nephrol Dial Transplant, 12, p. 1031-33
  31. Mori H, Kuroda Y, Imamura S, et al. (2003) "Hyponatremia and/or hyperkalemia in patients treated with the standard dose of trimethoprim-sulfamethoxazole." Intern Med, 42, p. 665-9
  32. Perazella MA (2000) "Drug-induced hyperkalemia: old culprits and new offenders." Am J Med, 109, p. 307-14
  33. Perazella MA, Mahnensmith RL (1997) "Hyperkalemia in the elderly: drugs exacerbate impaired potassium homeostasis." J Gen Intern Med, 12, p. 646-56
  34. Antoniou T, Gomes T, Juurlink DN, Loutfy MR, Glazier RH, Mamdani MM (2010) "Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study." Arch Intern Med, 170, p. 1045-9
  35. Lee SW, Park SW, Kang JM (2014) "Intraoperative hyperkalemia induced by administration of trimethoprim-sulfamethoxazole in a patient receiving angiotensin receptor blockers." J Clin Anesth, 26, p. 427-8
View all 35 references

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Drug and food interactions

Major

eplerenone food

Applies to: eplerenone

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of eplerenone. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In drug interaction studies, administration of a single 100 mg dose of eplerenone in combination with grapefruit juice resulted in a 25% increase in eplerenone systemic exposure (AUC). High blood levels of eplerenone can increase the risk of side effects including hyperkalemia. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with eplerenone.

References

  1. (2002) "Product Information. Inspra (eplerenone)." Searle
  2. (2021) "Product Information. Eplerenone (eplerenone)." MSN Laboratories Europe Ltd
  3. (2023) "Product Information. Eplerenone (Apotex) (eplerenone)." Apotex Pty Ltd

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Moderate

sulfamethoxazole food

Applies to: Septra IV (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

  1. Heelon MW, White M (1998) "Disulfiram-cotrimoxazole reaction." Pharmacotherapy, 18, p. 869-70
  2. Mergenhagen KA, Wattengel BA, Skelly MK, Clark CM, Russo TA (2020) "Fact versus fiction: a review of the evidence behind alcohol and antibiotic interactions." Antimicrob Agents Chemother, 64, e02167-19

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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.

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