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Drug Interactions between mycophenolic acid and Robitet 500

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

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Interactions between your drugs

Major

tetracycline mycophenolic acid

Applies to: Robitet 500 (tetracycline) and mycophenolic acid

MONITOR CLOSELY: Antibiotics which affect beta-glucuronidase producing bacteria in the intestine (e.g., aminoglycosides, cephalosporins, fluoroquinolones, and penicillins) may reduce systemic exposure to mycophenolic acid (MPA) products. The exact mechanism is not known; but is thought to be due to interference with enterohepatic recirculation of the active drug, MPA, via alterations in the gastrointestinal flora that are responsible for regenerating MPA from its glucuronide metabolite. One study reviewed 64 kidney transplant patients taking mycophenolate mofetil (MMF) who received either oral ciprofloxacin (500 mg twice daily for 7 days) or amoxicillin plus clavulanic acid (375 mg three times daily for at least 14 days). This study demonstrated approximately 50% reductions in the median trough MPA concentrations from baseline (MMF alone) in 3 days following the start of oral ciprofloxacin or amoxicillin plus clavulanic acid. The reductions in trough MPA concentrations tended to diminish within 14 days of antimicrobial therapy and cease within 3 days of the discontinuation of antibiotics. It is important to note that the trough level may not accurately reflect changes in the overall MPA exposure as the systemic exposure (AUC) was not evaluated in this study. In a study of 11 healthy volunteers who received a single-dose of MMF 1 gram on day 4 of a 5-day course of dual antibiotic therapy with both norfloxacin and metronidazole, the average AUC of MPA was reduced by 33% compared to the administration of MMF alone. However, when MMF was administered with norfloxacin alone or metronidazole alone (as opposed to the combination of MMF with norfloxacin and metronidazole), the reduction in AUC was not statistically significant. In a study of 12 healthy male volunteers, a single dose of MMF 1.5 grams was administered on day 8 of a 10-day course of trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily and no effect on the bioavailability of MPA was observed.

MANAGEMENT: Close clinical and laboratory monitoring for evidence of diminished immunosuppressive effects of mycophenolic acid products is recommended during concomitant therapy and shortly after antibiotic treatment is completed. Advise patients to report any symptoms of transplant rejection such as a decrease in organ function (e.g., reduced urine output for kidney transplant patients, shortness of breath and/or swelling in heart transplant patients, jaundice in liver transplant patients), and/or flu-like symptoms.

References

  1. "Product Information. CellCept (mycophenolate mofetil)." Roche Laboratories PROD (2001):
  2. "Product Information. Myfortic (mycophenolic acid)." Novartis Pharmaceuticals (2004):
  3. gao s, sun r, singh r, et al. "The role of gut microbial beta-glucuronidases (gmGUS) in drug disposition and development. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9717552/" (2023):
  4. "Product Information. Mycophenolate (Pharmacor) (mycophenolate mofetil)." Pharmacor Pty Ltd 00 (2022):
  5. "Product Information. ACH-Mycophenolate (mycophenolate mofetil)." Accord Healthcare (2022):
  6. "Product Information. CellCept (mycophenolate mofetil)." Roche Laboratories (2022):
  7. "Product Information. Myfenax (mycophenolate mofetil)." Teva UK Ltd (2023):
  8. "Product Information. Myfortic (mycophenolic acid)." Novartis Pharmaceuticals Pty Ltd (2022):
  9. "Product Information. Apo-Mycophenolic Acid (mycophenolic acid)." Apotex Incorporated (2022):
  10. "Product Information. Myfortic (mycophenolic acid)." Novartis Pharmaceuticals UK Ltd (2023):
  11. "Product Information. Mycophenolic Acid (mycophenolic acid)." Archis Pharma LLC (2022):
View all 11 references

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Drug and food interactions

Moderate

tetracycline food

Applies to: Robitet 500 (tetracycline)

ADJUST DOSING INTERVAL: Administration with food, particularly dairy products, significantly reduces tetracycline absorption. The calcium content of these foods forms nonabsorbable chelates with tetracycline.

MANAGEMENT: Tetracycline should be administered one hour before or two hours after meals.

References

  1. "Product Information. Achromycin (tetracycline)." Lederle Laboratories PROD (2001):
  2. "Product Information. Declomycin (demeclocycline)." Lederle Laboratories PROD (2001):

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Moderate

mycophenolic acid food

Applies to: mycophenolic acid

ADJUST DOSING INTERVAL: Administration of enteric coated mycophenolic acid with meals may alter its pharmacokinetics relative to administration in the fasting state. When mycophenolic acid 720 mg was administered with a high-fat meal, there was a 33% decrease in the peak plasma concentration (Cmax); a 3.5-hour increase in delay time for the rise of plasma mycophenolic acid; and a 5-hour delay in the time to reach peak plasma concentration (Tmax). However, no effect was observed on the systemic exposure of mycophenolic acid.

MANAGEMENT: To avoid variability in drug absorption between doses, enteric coated formulations of mycophenolic acid should be taken on an empty stomach, one hour before or two hours after food intake. The tablets should be swallowed whole and not crushed, chewed or divided in order to maintain the integrity of the enteric coating.

References

  1. "Product Information. Myfortic (mycophenolic acid)." Novartis Pharmaceuticals (2004):

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Moderate

tetracycline food

Applies to: Robitet 500 (tetracycline)

GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.

MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.

References

  1. Neuvonen PJ "Interactions with the absorption of tetracyclines." Drugs 11 (1976): 45-54
  2. Gothoni G, Neuvonen PJ, Mattila M, Hackman R "Iron-tetracycline interaction: effect of time interval between the drugs." Acta Med Scand 191 (1972): 409-11
  3. Venho VM, Salonen RO, Mattila MJ "Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal." Eur J Clin Pharmacol 14 (1978): 277-80
  4. "Product Information. Minocin (minocycline)." Lederle Laboratories PROD (2002):
  5. Campbell NR, Hasinoff BB "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol 31 (1991): 251-5
  6. Bateman FJ "Effects of tetracyclines." Br Med J 4 (1970): 802
  7. Neuvonen PJ, Gothoni G, Hackman R, Bjorksten K "Interference of iron with the absorption of tetracyclines in man." Br Med J 4 (1970): 532-4
  8. Greenberger NJ "Absorption of tetracyclines: interference by iron." Ann Intern Med 74 (1971): 792-3
  9. Neuvonen PJ, Penttila O "Effect of oral ferrous sulphate on the half-life of doxycycline in man." Eur J Clin Pharmacol 7 (1974): 361-3
  10. "Product Information. Seysara (sarecycline)." Allergan Inc (2018):
  11. "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc. (2018):
View all 11 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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.