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Drug Interactions between acetaminophen / caffeine / magnesium salicylate / phenyltoloxamine and kanamycin

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

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Interactions between your drugs

Moderate

kanamycin magnesium salicylate

Applies to: kanamycin and acetaminophen / caffeine / magnesium salicylate / phenyltoloxamine

MONITOR: The nephrotoxic effect of aminoglycosides may be potentiated by nonsteroidal anti-inflammatory drugs (NSAIDs), particularly if the latter had been given in high dosages for prolonged periods. Four children with cystic fibrosis who had been receiving chronic ibuprofen developed acute renal insufficiency shortly after initiation of IV aminoglycoside therapy for pulmonary exacerbations. An adolescent with CF who received intermittent, standard-dose ibuprofen during treatment with IV gentamicin also developed renal failure in addition to severe vestibular toxicity. Animal models suggest that renal prostaglandins may play a role in maintaining normal renal blood flow and glomerular filtration rate during the development of aminoglycoside nephrotoxicity, thus inhibition of their production by NSAIDs may worsen the renal damage.

MANAGEMENT: Whenever feasible, NSAID use should preferably be discontinued prior to initiating IV aminoglycoside therapy. If concomitant administration is necessary, hydration status as well as renal and vestibular functions should be closely monitored.

MONITOR: In premature infants, NSAIDs may increase the plasma concentrations of aminoglycosides. The proposed mechanism is decreased aminoglycoside clearance due to NSAID reduction of glomerular filtration rate, which is already low in premature infants. In a study of 20 preterm infants who had been given at least three days of amikacin or gentamicin therapy, mean peak plasma concentration increased by 17% and 33%, and mean trough concentration increased by 29% and 48%, respectively, on day 1 following administration of IV indomethacin for patent ductus arteriosus. Serum creatinine increased by 17%, while urine output and serum sodium decreased. Six patients developed hyponatremia.

MANAGEMENT: It may be advisable to consider reducing the dosage of aminoglycoside prior to initiation of NSAID therapy in infants. During coadministration, plasma antibiotic concentrations and renal function should be closely monitored, and the antibiotic dosage further adjusted as necessary.

References

  1. Zarfin Y, Koren G, Maresky D, et al. (1985) "Clinical and laboratory observations: possible indomethacin-aminoglycoside interaction in preterm infants." J Pediatr, 106, p. 511-3
  2. Scott CS, RetschBogart GZ, Henry MM (2001) "Renal failure and vestibular toxicity in an adolescent with cystic fibrosis receiving gentamicin and standard-dose ibuprofen." Pediat Pulm, 31, p. 314-6
  3. Kovesi TA, Swartz R, MacDonald N (1998) "Transient renal failure due to simultaneous ibuprofen and aminoglycoside therapy in children with cystic fibrosis." N Engl J Med, 338, p. 65-6
  4. Gagliardi L (1985) "Possible indomethacin-aminoglycoside interaction in preterm infants." J Pediatr, 107, p. 991-2
  5. Farag MM, Mikhail MR, Abdel-Meguid E, Abdel-Tawab S (1996) "Assessment of gentamicin-induced nephrotoxicity in rats treated with low doses of ibuprofen and diclofenac sodium." Clin Sci, 91, p. 187-91
  6. Assael BM, Chiabrando C, Gagliardi L, Noseda A, Bamonte F, Salmona M (1985) "Prostaglandins and aminoglycoside nephrotoxicity." Toxicol Appl Pharmacol, 78, p. 386-94
View all 6 references

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Drug and food interactions

Major

acetaminophen food

Applies to: acetaminophen / caffeine / magnesium salicylate / phenyltoloxamine

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

References

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA (1985) "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med, 145, p. 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA (1986) "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA, 255, p. 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB (1986) "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med, 104, p. 399-404
  4. Thummel KE, Slattery JT, Nelson SD (1988) "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther, 245, p. 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL (1980) "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA, 244, p. 251-3
  6. Kartsonis A, Reddy KR, Schiff ER (1986) "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med, 105, p. 138-9
  7. Prescott LF, Critchley JA (1983) "Drug interactions affecting analgesic toxicity." Am J Med, 75, p. 113-6
  8. (2002) "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical
  9. Whitcomb DC, Block GD (1994) "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA, 272, p. 1845-50
  10. Bonkovsky HL (1995) "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA, 274, p. 301
  11. Nelson EB, Temple AR (1995) "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA, 274, p. 301
  12. Zimmerman HJ, Maddrey WC (1995) "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology, 22, p. 767-73
View all 12 references

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Moderate

phenyltoloxamine food

Applies to: acetaminophen / caffeine / magnesium salicylate / phenyltoloxamine

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 (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

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Moderate

magnesium salicylate food

Applies to: acetaminophen / caffeine / magnesium salicylate / phenyltoloxamine

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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Minor

caffeine food

Applies to: acetaminophen / caffeine / magnesium salicylate / phenyltoloxamine

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

References

  1. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR (1996) "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy, 16, p. 1046-52

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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.

See also

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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.

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