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Drug Interactions between ampicillin / probenecid and Combiflex ES

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

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Interactions between your drugs

Moderate

probenecid magnesium salicylate

Applies to: ampicillin / probenecid and Combiflex ES (acetaminophen / caffeine / magnesium salicylate / phenyltoloxamine)

GENERALLY AVOID: Large, anti-inflammatory doses of salicylates may inhibit the uricosuric effect of probenecid. The mechanism of interaction has not been established. In contrast, low, daily antiplatelet doses do not seem to interact. In a study of 11 patients with gouty arthritis receiving a stable dosage of probenecid for at least three months, no significant effects on serum levels or 24-hour urinary excretion of uric acid were observed during coadministration with enteric-coated aspirin 325 mg/day, taken simultaneously with probenecid or 6 hours after.

MANAGEMENT: Large doses of salicylates should be avoided in patients who require probenecid for the treatment of hyperuricemia or gout. However, occasional use of low dosages for analgesia or daily use of cardioprotective dosages should generally not be a concern.

References

  1. Diamond JS, Paolino JS "Evidence for a postsecretory reabsorptive site for uric acid in man." J Clin Invest 52 (1973): 1491-9
  2. Regal RE "Aspirin and uricosurics: interaction revisited." Drug Intell Clin Pharm 21 (1987): 219-20
  3. Harris M, Bryant LR, Danaher P, Alloway J "Effect of low dose daily aspirin on serum urate levels and urinary excretion in patients receiving probenecid for gouty arthritis." J Rheumatol 27 (2000): 2873-6
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 4 references

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Minor

ampicillin probenecid

Applies to: ampicillin / probenecid and ampicillin / probenecid

Probenecid may increase the plasma concentrations and half-lives of penicillins. The mechanism is competitive inhibition by probenecid of the renal tubular secretion of penicillins. While this interaction is often exploited to enhance the antibacterial effect of penicillins, toxicity may occur and should be considered if high penicillin dosages are administered intravenously.

References

  1. Sommers DK, Schoeman HS "Drug interactions with urate excretion in man?" Eur J Clin Pharmacol 32 (1987): 499-502
  2. Waller ES, Sharanevych MA, Yakatan GJ "The effect of probenecid on nafcillin disposition." J Clin Pharmacol 22 (1982): 482-9
  3. Shanson DC, McNabb R, Hajipieris P "The effect of probenecid on serum amoxycillin concentrations up to 18 hours after a single 3g oral dose of amoxycillin: possible implications for preventing endocarditis." J Antimicrob Chemother 13 (1984): 629-32
  4. Sutherland R, Croydon EA, Rolinson GN "Amoxycillin: a new semi-synthetic penicillin." Br Med J 3 (1972): 13-6
  5. Allen MB, Fitzpatrick RW, Barratt A, Cole RB "The use of probenecid to increase the serum amoxycillin levels in patients with bronchiectasis." Respir Med 84 (1990): 143-6
  6. Gibaldi M, Schwartz MA "Apparent effect of probenecid on the distribution of penicillins in man." Clin Pharmacol Ther 9 (1968): 345-9
View all 6 references

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Minor

probenecid acetaminophen

Applies to: ampicillin / probenecid and Combiflex ES (acetaminophen / caffeine / magnesium salicylate / phenyltoloxamine)

Probenecid may slightly increase the therapeutic effects of acetaminophen. At usual doses, however, no intervention appears to be necessary.

References

  1. Abernethy DR, Greenblatt DJ, Ameer B, Shader RI "Probenecid impairment of acetaminophen and lorazepam clearance: direct inhibition of ether glucuronide formation." J Pharmacol Exp Ther 234 (1985): 345-9
  2. Kamali F, Fry JR, Bell GD "Salivary excretion of paracetamol in man." J Pharm Pharmacol 39 (1987): 150-2

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Drug and food interactions

Major

acetaminophen food

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

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Moderate

ampicillin food

Applies to: ampicillin / probenecid

ADJUST DOSING INTERVAL: Certain penicillins may exhibit reduced gastrointestinal absorption in the presence of food. The therapeutic effect of the antimicrobial may be reduced.

MANAGEMENT: The interacting penicillin should be administered one hour before or two hours after meals. Penicillin V and amoxicillin are not affected by food and may be given without regard to meals.

References

  1. Neu HC "Antimicrobial activity and human pharmacology of amoxicillin." J Infect Dis 129 (1974): s123-31
  2. Welling PG, Huang H, Koch PA, Madsen PO "Bioavailability of ampicillin and amoxicillin in fasted and nonfasted subjects." J Pharm Sci 66 (1977): 549-52
  3. McCarthy CG, Finland M "Absorption and excretion of four penicillins." N Engl J Med 263 (1960): 315-26
  4. Cronk GA, Wheatley WB, Fellers GF, Albright H "The relationship of food intake to the absorption of potassium alpha-phenoxyethyl penicillin and potassium phenoxymethyl penicillin from the gastrointestinal tract." Am J Med Sci 240 (1960): 219-25
  5. Klein JO, Sabath LD, Finland M "Laboratory studies on oxacillin. I: in vitro activity against staphylococci and some other bacterial pathogens. II: absorption and urinary excretion in normal young." Am J Med Sci 245 (1963): 399-411
  6. Neuvonen PJ, Elonen E, Pentikainen PJ "Comparative effect of food on absorption of ampicillin and pivampicillin." J Int Med Res 5 (1977): 71-6
View all 6 references

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Moderate

phenyltoloxamine food

Applies to: Combiflex ES (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 "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

magnesium salicylate food

Applies to: Combiflex ES (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. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn PROD (2002):

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Minor

caffeine food

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