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Drug Interactions between nalidixic acid and TheraCys

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

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Major

nalidixic acid BCG

Applies to: nalidixic acid and TheraCys (bcg)

GENERALLY AVOID: Antibiotics may interfere with the anti-tumor activity of intravesical BCG, which contains a live, attenuated strain of Mycobacterium bovis. Some researchers have suggested that antibiotic therapy prior to or concurrently with BCG therapy may affect therapeutic efficacy via changes in the urinary microbiome. It is considered contraindicated to use intravesical BCG in patients with concurrent febrile illness, active tuberculosis, and/or urinary tract infections. Intravesical BCG is sensitive to most antibiotics, particularly those that are routinely used in the treatment of tuberculosis such as streptomycin, para-aminosalicylic acid (PAS), isoniazid (INH), rifampin, and ethambutol. It is reportedly not sensitive to pyrazinamide or cycloserine. Regardless of clinical susceptibility data, however, most antibacterials may still interfere with BCG in the bladder due to their high urinary recovery. One retrospective study in 276 high-risk non-muscle invasive bladder cancer patients receiving intravesical BCG reported a significantly higher 5-year recurrence-free survival rate in patients who did not receive antibiotic therapy than in those treated with long-course (>=7 days) antibiotics (ciprofloxacin, levofloxacin, cefaclor, cefpodoxime, or cefixime).

MANAGEMENT: Intravesical BCG should not be used in individuals with concurrent infections. For patients being treated with antibiotics, intravesical instillations of BCG should generally be postponed until completion of antibiotic therapy. If a bacterial urinary tract infection (UTI) occurs, therapy with intravesical BCG should be postponed or interrupted until complete resolution of the infection (e.g., negative urine culture and completion of antibiotic(s) and/or urinary antiseptic(s)), not only because antimicrobial administration may diminish the anti-tumor efficacy of BCG, but also because the combination of a UTI and BCG-induced cystitis may lead to more severe adverse effects in the genitourinary tract. There are no data to suggest that the acute, local urinary tract toxicity common with intravesical administration of BCG is due to mycobacterial infection, thus antituberculosis drugs should not be used to prevent or treat the local, irritative toxicities of intravesical BCG.

References

  1. Durek C, Rusch-Gerdes S, Jocham D, Bohle A (1999) "Interference of modern antibacterials with bacillus Calmette-Guerin viability." J Urol, 162, p. 1959-62
  2. (2021) "Product Information. OncoTICE (BCG)." Merck Sharp & Dohme (UK) Ltd
  3. (2022) "Product Information. Tice BCG Live (for intravesical use) (BCG)." Merck Sharp & Dohme LLC
  4. (2019) "Product Information. OncoTICE (BCG)." Organon
  5. (2021) "Product Information. Verity-BCG (BCG)." Verity Pharmaceuticals Inc.
  6. Pak S, Kim SY, kim sh, et al. (2023) Association between antibiotic treatment and the efficacy of intravesical BCG therapy in patients with high-risk non-muscle invasive bladder cancer. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051584/
View all 6 references

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Drug and food interactions

Moderate

nalidixic acid food

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

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Moderate

nalidixic acid food

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

  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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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.

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