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Interactions between Fosfree and Nalidixic acid

1 drug interaction and 15 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

nalidixic acid multivitamins with minerals

Applies to: nalidixic acid and Fosfree (multivitamin with minerals)
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)
  1. "Product Information. Neggram (nalidixic acid)." Sanofi Winthrop Pharmaceuticals

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

nalidixic acid multivitamins with minerals

Applies to: 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)
  1. "Product Information. Neggram (nalidixic acid)." Sanofi Winthrop Pharmaceuticals
Moderate:

nalidixic acid Caffeine

Applies to: 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 (17)
  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

Disease interactions

13 potential interactions Applies to: 13 conditions, including Rheumatoid Arthritis, Peripheral Neuropathy, Diarrhea, Myasthenia Gravis, and Tendonitis.

Central Nervous System Disorders

Major:

nalidixic acid

Nalidixic acid has a major potential interaction with Central Nervous System Disorders.

Quinolones may cause CNS stimulation manifested as tremors, agitation, restlessness, anxiety, confusion, hallucinations, paranoia, insomnia, toxic psychosis, and/or seizures. Benign intracranial hypertension has also been reported. Therapy with quinolones should be administered cautiously in patients with or predisposed to seizures or other CNS abnormalities. In addition, these patients should be advised to avoid the consumption of caffeine-containing products during therapy with some quinolones, most notably ciprofloxacin, enoxacin, and cinoxacin, since these agents can substantially reduce the clearance of caffeine and other methylxanthines, potentially resulting in severe CNS reactions.

Dehydration

Moderate:

nalidixic acid

Nalidixic acid has a moderate potential interaction with Dehydration.

Crystalluria has been reported rarely during quinolone therapy. Although it is not expected to occur under normal circumstances with usual recommended dosages, patients who are dehydrated (e.g., due to severe diarrhea or vomiting) may be at increased risk and should be encouraged to consume additional amounts of liquid or given intravenous fluid to ensure an adequate urinary output. Alkalinity of the urine should be avoided, since it may also increase the risk of crystalluria. Renal function tests should be performed periodically during prolonged therapy (> 2 weeks).

Diabetes Mellitus

Moderate:

nalidixic acid

Nalidixic acid has a moderate potential interaction with Diabetes Mellitus.

The use of certain quinolones has been associated with disturbances in blood glucose homeostasis possibly stemming from effects on pancreatic beta cell ATP-sensitive potassium channels that regulate insulin secretion. Hypoglycemia and, less frequently, hyperglycemia have been reported, although the latter may also occur due to infection alone. Hypoglycemia has usually occurred in patients with diabetes receiving concomitant oral hypoglycemic agents and/or insulin. Administration of ciprofloxacin, levofloxacin, norfloxacin, and especially gatifloxacin in patients treated with sulfonylureas or other oral hypoglycemic agents has resulted in severe, refractory hypoglycemia and hypoglycemic coma. Elderly patients and patients with reduced renal function are particularly susceptible. Blood glucose should be monitored more closely whenever quinolones are prescribed to patients with diabetes. Gatifloxacin has been known to cause hypoglycemic episodes generally within the first 3 days of therapy and sometimes even after the first dose, while hyperglycemia usually occurs 4 to 10 days after initiation of therapy. Patients should be counseled to recognize symptoms of hypoglycemia such as headache, dizziness, drowsiness, nausea, tremor, weakness, hunger, excessive perspiration, and palpitations. If hypo- or hyperglycemia occur during quinolone therapy, patients should initiate appropriate remedial therapy immediately, discontinue the antibiotic, and contact their physician.

Diarrhea

Moderate:

nalidixic acid

Nalidixic acid has a moderate potential interaction with Diarrhea.

Crystalluria has been reported rarely during quinolone therapy. Although it is not expected to occur under normal circumstances with usual recommended dosages, patients who are dehydrated (e.g., due to severe diarrhea or vomiting) may be at increased risk and should be encouraged to consume additional amounts of liquid or given intravenous fluid to ensure an adequate urinary output. Alkalinity of the urine should be avoided, since it may also increase the risk of crystalluria. Renal function tests should be performed periodically during prolonged therapy (> 2 weeks).

Liver Disease

Major:

nalidixic acid

Nalidixic acid has a major potential interaction with Liver Disease.

Nalidixic acid is primarily metabolized by the liver and may accumulate in patients with impaired hepatic function. Therapy with nalidixic acid should be administered cautiously in patients with liver disease.

Myasthenia Gravis

Major:

nalidixic acid

Nalidixic acid has a major potential interaction with Myasthenia Gravis.

Fluoroquinolones have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolones use in persons with myasthenia gravis. Fluoroquinolones should be avoided in patients with history of myasthenia gravis.

Noninfectious Colitis

Major:

nalidixic acid

Nalidixic acid has a major potential interaction with Noninfectious Colitis.

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

Organ Transplant

Major:

nalidixic acid

Nalidixic acid has a major potential interaction with Organ Transplant.

Tendonitis and ruptures of the shoulder, hand, and Achilles tendons have been reported in patients receiving quinolones, both during and after treatment. Avoid the use of these agents in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture. Therapy with quinolones should be administered cautiously in patients with patients with kidney, heart, and lung transplant, since it may delay the recognition or confound the diagnosis of a quinolone-induced musculoskeletal effect. Factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. It is recommended to discontinue these agents if, at any time during therapy, pain, inflammation or rupture of a tendon develops and institute appropriate treatment.

Peripheral Neuropathy

Major:

nalidixic acid

Nalidixic acid has a major potential interaction with Peripheral Neuropathy.

The use of quinolones has been associated with an increased risk of peripheral neuropathy. Monitor closely and discontinue their use in patients experiencing symptoms of peripheral neuropathy. It is recommended to avoid these agents in patients who have previously experienced peripheral neuropathy.

Renal Dysfunction

Major:

nalidixic acid

Nalidixic acid has a major potential interaction with Renal Dysfunction.

Tendonitis and ruptures of the shoulder, hand, and Achilles tendons have been reported in patients receiving quinolones, both during and after treatment. Avoid the use of these agents in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture. Therapy with quinolones should be administered cautiously in patients with patients with kidney, heart, and lung transplant, since it may delay the recognition or confound the diagnosis of a quinolone-induced musculoskeletal effect. Factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. It is recommended to discontinue these agents if, at any time during therapy, pain, inflammation or rupture of a tendon develops and institute appropriate treatment.

Rheumatoid Arthritis

Major:

nalidixic acid

Nalidixic acid has a major potential interaction with Rheumatoid Arthritis.

Tendonitis and ruptures of the shoulder, hand, and Achilles tendons have been reported in patients receiving quinolones, both during and after treatment. Avoid the use of these agents in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture. Therapy with quinolones should be administered cautiously in patients with patients with kidney, heart, and lung transplant, since it may delay the recognition or confound the diagnosis of a quinolone-induced musculoskeletal effect. Factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. It is recommended to discontinue these agents if, at any time during therapy, pain, inflammation or rupture of a tendon develops and institute appropriate treatment.

Tendonitis

Major:

nalidixic acid

Nalidixic acid has a major potential interaction with Tendonitis.

Tendonitis and ruptures of the shoulder, hand, and Achilles tendons have been reported in patients receiving quinolones, both during and after treatment. Avoid the use of these agents in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture. Therapy with quinolones should be administered cautiously in patients with patients with kidney, heart, and lung transplant, since it may delay the recognition or confound the diagnosis of a quinolone-induced musculoskeletal effect. Factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. It is recommended to discontinue these agents if, at any time during therapy, pain, inflammation or rupture of a tendon develops and institute appropriate treatment.

Vomiting

Moderate:

nalidixic acid

Nalidixic acid has a moderate potential interaction with Vomiting.

Crystalluria has been reported rarely during quinolone therapy. Although it is not expected to occur under normal circumstances with usual recommended dosages, patients who are dehydrated (e.g., due to severe diarrhea or vomiting) may be at increased risk and should be encouraged to consume additional amounts of liquid or given intravenous fluid to ensure an adequate urinary output. Alkalinity of the urine should be avoided, since it may also increase the risk of crystalluria. Renal function tests should be performed periodically during prolonged therapy (> 2 weeks).

More resources

Fosfree

A total of 112 drugs are known to interact with Fosfree.

nalidixic acid

A total of 320 drugs are known to interact with nalidixic acid.

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.