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Drug Interactions between Demi-Cof and Sulfatrim Pediatric

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

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Major

trimethoprim potassium iodide

Applies to: Sulfatrim Pediatric (sulfamethoxazole / trimethoprim) and Demi-Cof (chlorpheniramine / codeine / phenylephrine / potassium iodide)

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. "Product Information. Bactrim (sulfamethoxazole-trimethoprim)." Roche Laboratories (2022):
  2. 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
  3. Greenberg S, Reiser IW, Chou SY "Hyperkalemia with high-dose trimethoprim-sulfamethoxazole therapy." Am J Kidney Dis 22 (1993): 603-6
  4. 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
  5. Velazquez H, Perazella MA, Wright FS, Ellison DH "Renal mechanism of trimethoprim-induced hyperkalemia." Ann Intern Med 119 (1993): 296-301
  6. Smith GW, Cohen SB "Hyperkalaemia and non-oliguric renal failure associated with trimethoprim." Br Med J 308 (1994): 454
  7. Modest GA, Price B, Mascoli N "Hyperkalemia in elderly patients receiving standard doses of trimethoprim-sulfamethoxazole." Ann Intern Med 120 (1994): 437
  8. Pennypacker LC, Mintzer J, Pitner J "Hyperkalemia in elderly patients receiving standard doses of trimethoprim-sulfamethoxazole." Ann Intern Med 120 (1994): 437
  9. Canaday DH, Johnson JR "Hyperkalemia in elderly patients receiving standard doses of trimethoprim-sulfamethoxazole." Ann Intern Med 120 (1994): 438
  10. Lawson DH "Adverse reactions to potassium chloride." Q J Med 43 (1974): 433-40
  11. Hsu I, Wordell CJ "Hyperkalemia and high-dose trimethoprim/sulfamethoxazole." Ann Pharmacother 29 (1995): 427-9
  12. Marinella MA "Reversible hyperkalemia associated with trimethoprim-sulfamethoxazole." Am J Med Sci 310 (1995): 115-7
  13. 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
  14. Alappan R, Perazella MA, Buller GK "Hyperkalemia in hospitalized patients treated with trimethoprim-sulfamethoxazole." Ann Intern Med 124 (1996): 316-20
  15. 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
  16. Thomas RJ "Severe hyperkalemia with trimethoprim-quinapril." Ann Pharmacother 30 (1996): 413-4
  17. Eiam-Ong S, Kurtzman NA, Sabatini S "Studies on the mechanism of trimethoprim-induced hyperkalemia." Kidney Int 49 (1996): 1372-8
  18. Perazella MA, Mahnensmith RL "Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication regardless of dose." Clin Nephrol 46 (1996): 187-92
  19. 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
  20. Perazella MA, Alappan R, Buller GK "Hyperkalemia and trimethoprim-sulfamethoxazole." Ann Intern Med 125 (1996): 1015
  21. 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
  22. Marinella MA "Severe hyperkalemia associated with trimethoprim-sulfamethoxazole and spironolactone." Infect Dis Clin Pract 6 (1997): 256-8
  23. 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
  24. Marinella MA "Trimethoprim-sulfamethoxazole associated with hyperkalemia." West J Med 167 (1997): 356-8
  25. 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
  26. 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
  27. Marcy TR, Ripley TL "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm 63 (2006): 49-58
  28. "Prevent-ERR: sulfamethoxazole and trimethoprim-induced hyperkalemia." ISMP Medication Safety Alert! 13(Dec 4) (2008): 3
  29. 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
  30. 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
  31. 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
  32. Perazella MA "Drug-induced hyperkalemia: old culprits and new offenders." Am J Med 109 (2000): 307-14
  33. Perazella MA, Mahnensmith RL "Hyperkalemia in the elderly: drugs exacerbate impaired potassium homeostasis." J Gen Intern Med 12 (1997): 646-56
  34. 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
  35. 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
View all 35 references

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Moderate

codeine chlorpheniramine

Applies to: Demi-Cof (chlorpheniramine / codeine / phenylephrine / potassium iodide) and Demi-Cof (chlorpheniramine / codeine / phenylephrine / potassium iodide)

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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. Hamilton MJ, Bush M, Smith P, Peck AW "The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man." Br J Clin Pharmacol 14 (1982): 791-7
  2. Stambaugh JE, Lane C "Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination." Cancer Invest 1 (1983): 111-7
  3. Sotaniemi EA, Anttila M, Rautio A, et al. "Propranolol and sotalol metabolism after a drinking party." Clin Pharmacol Ther 29 (1981): 705-10
  4. Grabowski BS, Cady WJ, Young WW, Emery JF "Effects of acute alcohol administration on propranolol absorption." Int J Clin Pharmacol Ther Toxicol 18 (1980): 317-9
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF "The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam." Clin Pharmacol Ther 43 (1988): 412-9
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol 11 (1977): 345-9
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl) 73 (1981): 381-3
  8. Naylor GJ, McHarg A "Profound hypothermia on combined lithium carbonate and diazepam treatment." Br Med J 2 (1977): 22
  9. Stovner J, Endresen R "Intravenous anaesthesia with diazepam." Acta Anaesthesiol Scand 24 (1965): 223-7
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF "Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation." J Pharm Pharmacol 36 (1984): 244-7
  11. Feldman SA, Crawley BE "Interaction of diazepam with the muscle-relaxant drugs." Br Med J 1 (1970): 336-8
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B "Propranolol interactions with diazepam, lorazepam and alprazolam." Clin Pharmacol Ther 36 (1984): 451-5
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF "Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic." Psychopharmacology (Berl) 96 (1988): 63-6
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I "Midazolam-morphine sedative interaction in patients." Anesth Analg 68 (1989): 282-5
  15. "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc PROD
  16. Greiff JMC, Rowbotham D "Pharmacokinetic drug interactions with gastrointestinal motility modifying agents." Clin Pharmacokinet 27 (1994): 447-61
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G "The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine." Acta Psychiatr Scand 80 Suppl (1989): 95-8
  18. Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9
  19. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical PROD (2001):
  20. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories PROD (2001):
  21. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) PROD (2001):
  22. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  23. "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company PROD (2001):
  24. "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals PROD (2001):
  25. Miller LG "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med 158 (1998): 2200-11
  26. "Product Information. Precedex (dexmedetomidine)." Abbott Pharmaceutical PROD (2001):
  27. "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals PROD (2001):
  28. Ferslew KE, Hagardorn AN, McCormick WF "A fatal interaction of methocarbamol and ethanol in an accidental poisoning." J Forensic Sci 35 (1990): 477-82
  29. Plushner SL "Valerian: valeriana officinalis." Am J Health Syst Pharm 57 (2000): 328-35
  30. "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc (2002):
  31. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals (2002):
  32. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  33. Cerner Multum, Inc. "Australian Product Information." O 0
  34. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  35. "Product Information. Belsomra (suvorexant)." Merck & Co., Inc (2014):
  36. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
View all 36 references

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Drug and food interactions

Moderate

chlorpheniramine food

Applies to: Demi-Cof (chlorpheniramine / codeine / phenylephrine / potassium iodide)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and 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 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. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
View all 4 references

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Moderate

codeine food

Applies to: Demi-Cof (chlorpheniramine / codeine / phenylephrine / potassium iodide)

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. 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.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

References

  1. Linnoila M, Hakkinen S "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther 15 (1974): 368-73
  2. Sturner WQ, Garriott JC "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA 223 (1973): 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol 41 (1991): 147-52
  4. Levine B, Saady J, Fierro M, Valentour J "A hydromorphone and ethanol fatality." J Forensic Sci 29 (1984): 655-9
  5. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol 19 (1985): 398-401
  6. Carson DJ "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet 1 (1977): 894-7
  7. Rosser WW "The interaction of propoxyphene with other drugs." Can Med Assoc J 122 (1980): 149-50
  8. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM "Distalgesic and ethanol-impaired function." Lancet 2 (1982): 384
  9. Kiplinger GF, Sokol G, Rodda BE "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther 212 (1974): 175-80
View all 9 references

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Moderate

sulfamethoxazole food

Applies to: Sulfatrim Pediatric (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 "Disulfiram-cotrimoxazole reaction." Pharmacotherapy 18 (1998): 869-70
  2. 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

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Moderate

phenylephrine food

Applies to: Demi-Cof (chlorpheniramine / codeine / phenylephrine / potassium iodide)

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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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.