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Drug Interactions between aminophylline / guaifenesin and NegGram

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

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Interactions between your drugs

Moderate

nalidixic acid aminophylline

Applies to: NegGram (nalidixic acid) and aminophylline / guaifenesin

MONITOR: Some fluoroquinolones have been shown to decrease the hepatic metabolism of theophyllines. The mechanism is inhibition of CYP450 1A2 hepatic metabolism. Patients with chronic obstructive pulmonary disease, congestive heart failure, or cirrhosis may have slower theophylline clearance rates; therefore, they may be at greater risk of developing theophylline toxicity. This drug combination may increase the risk of seizures, especially in the elderly. Interpatient variability of this effect makes it prudent to monitor patients who may not tolerate a small increase in theophylline levels during concurrent fluoroquinolone therapy.

MANAGEMENT: Interpatient variability of this effect makes it prudent to monitor patients who may not tolerate a small increase in theophylline levels. Levofloxacin, sparfloxacin, and lomefloxacin have been reported to cause minor or no changes in theophylline levels and may be considered as alternatives. Patients should be advised to report any signs of theophylline toxicity including nausea, vomiting, diarrhea, headache, restlessness, insomnia, seizures, or irregular heartbeat to their physicians.

References

  1. Ball P (1986) "Ciprofloxacin: an overview of adverse experiences." J Antimicrob Chemother, 18, p. 187-93
  2. Raoof S, Wollschlager C, Khan FA (1987) "Ciprofloxacin increases serum levels of theophylline." Am J Med, 82, p. 115-8
  3. Sano M, Yamamoto I, Ueda J, Yoskikawa E, Yamashina H, Goto M (1987) "Comparative pharmacokinetics of theophylline following two fluoroquinolones co-administration." Eur J Clin Pharmacol, 32, p. 431-2
  4. Bowles SK, Popovski Z, Rybak MJ, Beckman HB, Edwards DJ (1988) "Effect of norfloxacin on theophylline pharmacokinetics at steady state." Antimicrob Agents Chemother, 32, p. 510-12
  5. Green L, Clark J (1989) "Fluoroquinolones and theophylline toxicity: norfloxacin." JAMA, 262, p. 2383
  6. Ho G, Tierney MG, Dales RE (1988) "Evaluation of the effect of norfloxacin on the pharmacokinetics of theophylline." Clin Pharmacol Ther, 44, p. 35-8
  7. Davis RL, Kelly HW, Quenzer RW, Standefer J, Steinberg B, Gallegos J (1989) "Effect of norfloxacin on theophyllin metabolism." Antimicrob Agents Chemother, 33, p. 212-4
  8. Wijnands WJ, Vree TB (1988) "Interaction between the fluoroquinolones and the bronchodilator theophylline." J Antimicrob Chemother, 22, p. 109-14
  9. Wijnands WJ, Vree TB, Baars AM, van Herwaarden CL (1987) "Steady-state kinetics of the quinolone derivatives ofloxacin, enoxacin, ciprofloxacin and pefloxacin during maintneance treatment with theophylline." Drugs, 34, p. 159-69
  10. Gregoire SL, Grasela TH Jr, Freer JP, Tack KJ, Schentag JJ (1987) "Inhibition of theophylline clearance by coadministered ofloxacin without alteraction of theophylline effects." Antimicrob Agents Chemother, 31, p. 375-8
  11. Upton RA (1991) "Pharmacokinetic interactions between theophylline and other medication (Part I)." Clin Pharmacokinet, 20, p. 66-80
  12. Hooper DC, Wolfson JS (1985) "The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans." Antimicrob Agents Chemother, 28, p. 716-21
  13. Covelli HD, Knodel AR, Heppner BT (1985) "Predisposing factors to apparent theophylline-induced seizures." Ann Allergy, 54, p. 411-5
  14. Grasela TH, Dreis MW (1992) "An evaluation of the quinolone-theophylline interaction using the Food and Drug Administration spontaneous reporting system." Arch Intern Med, 152, p. 617-21
  15. (2001) "Product Information. Cinobac (cinoxacin)." Oclassen Pharmaceuticals Inc
  16. Segev S. Rehavi M, Rubinstein E (1988) "Quinolones, theophylline, and diclofenac interactions with the gamma-aminobutyric acid receptor." Antimicrob Agents Chemother, 32, p. 1624-6
View all 16 references

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Drug and food interactions

Moderate

nalidixic acid food

Applies to: NegGram (nalidixic acid)

ADJUST DOSING INTERVAL: Oral preparations that contain magnesium, aluminum, or calcium may significantly decrease the gastrointestinal absorption of nalidixic acid. Absorption may also be reduced by sucralfate, which contains aluminum, as well as other polyvalent cations such as iron and zinc. The mechanism is chelation of nalidixic acid by polyvalent cations, forming a complex that is poorly absorbed from the gastrointestinal tract.

MANAGEMENT: When coadministration cannot be avoided, nalidixic acid should be dosed at least 2 hours before or 2 hours after polyvalent cation-containing products to minimize the potential for interaction.

References

  1. "Product Information. Neggram (nalidixic acid)." Sanofi Winthrop Pharmaceuticals

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Moderate

nalidixic acid food

Applies to: NegGram (nalidixic acid)

MONITOR: Coadministration with certain quinolones may increase the plasma concentrations and pharmacologic effects of caffeine due to inhibition of the CYP450 1A2 metabolism of caffeine. Quinolones that may inhibit CYP450 1A2 include ciprofloxacin, enoxacin, grepafloxacin, nalidixic acid, norfloxacin, pipemidic acid, and pefloxacin (not all commercially available). In healthy volunteers, enoxacin (100 to 400 mg twice daily) increased systemic exposure (AUC) of caffeine by 2- to 5-fold and reduced its clearance by approximately 80%. Pipemidic acid (400 to 800 mg twice daily) increased AUC of caffeine by 2- to 3-fold and reduced its clearance by approximately 60%. Ciprofloxacin (250 to 750 mg twice daily) increased AUC and elimination half-life of caffeine by 50% to over 100%, and reduced its clearance by 30% to 50%. Norfloxacin 400 mg twice daily increased caffeine AUC by 16%, while 800 mg twice daily increased caffeine AUC by 52% and reduced its clearance by 35%. Pefloxacin (400 mg twice daily) has been shown to reduce caffeine clearance by 47%.

MANAGEMENT: Patients using caffeine-containing products should be advised that increased adverse effects such as headache, tremor, restlessness, nervousness, insomnia, tachycardia, and blood pressure increases may occur during coadministration with quinolones that inhibit CYP450 1A2. Caffeine intake should be limited when taking high dosages of these quinolones. If an interaction is suspected, other quinolones such as gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, and ofloxacin may be considered, since they are generally believed to have little or no effect on CYP450 1A2 or have been shown not to interact with caffeine.

References

  1. Polk RE (1989) "Drug-drug interactions with ciprofloxacin and other fluoroquinolones." Am J Med, 87, s76-81
  2. Healy DP, Polk RE, Kanawati L, Rock DT, Mooney ML (1989) "Interaction between oral ciprofloxacin and caffeine in normal volunteers." Antimicrob Agents Chemother, 33, p. 474-8
  3. Harder S, Fuhr U, Staib AH, Wolf T (1989) "Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations." Am J Med, 87, p. 89-91
  4. Carbo ML, Segura J, De la Torre R, et al. (1989) "Effect of quinolones on caffeine disposition." Clin Pharmacol Ther, 45, p. 234-40
  5. (1993) "Product Information. Penetrax (enoxacin)." Rhone-Poulenc Rorer, Collegeville, PA.
  6. Mahr G, Sorgel F, Granneman GR, et al. (1992) "Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine." Clin Pharmacokinet, 22, p. 90-7
  7. (2002) "Product Information. Cipro (ciprofloxacin)." Bayer
  8. (2001) "Product Information. Noroxin (norfloxacin)." Merck & Co., Inc
  9. Staib AH, Stille W, Dietlein G, et al. (1987) "Interaction between quinolones and caffeine." Drugs, 34 Suppl 1, p. 170-4
  10. Stille W, Harder S, Micke S, et al. (1987) "Decrease of caffeine elimination in man during co-administration of 4-quinolones." J Antimicrob Chemother, 20, p. 729-34
  11. Harder S, Staib AH, Beer C, Papenburg A, Stille W, Shah PM (1988) "4-Quinolones inhibit biotransformation of caffeine." Eur J Clin Pharmacol, 35, p. 651-6
  12. Nicolau DP, Nightingale CH, Tessier PR, et al. (1995) "The effect of fleroxacin and ciprofloxacin on the pharmacokinetics of multiple dose caffeine." Drugs, 49 Suppl 2, p. 357-9
  13. (2001) "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome
  14. Carrillo JA, Benitez J (2000) "Clinically significant pharmacokinetic interactions between dietary caffeine and medications." Clin Pharmacokinet, 39, p. 127-53
  15. Fuhr U, Wolff T, Harder S, Schymanski P, Staib AH (1990) "Quinolone inhibition of cytochrome P-450 dependent caffeine metabolism in human liver microsomes." Drug Metab Dispos, 18, p. 1005-10
  16. Kinzig-Schippers M, Fuhr U, Zaigler M, et al. (1999) "Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2." Clin Pharmacol Ther, 65, p. 262-74
  17. Healy DP, Schoenle JR, Stotka J, Polk RE (1991) "Lack of interaction between lomefloxacin and caffeine in normal volunteers." Antimicrob Agents Chemother, 35, p. 660-4
View all 17 references

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Moderate

aminophylline food

Applies to: aminophylline / guaifenesin

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 (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
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.

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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