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Drug Interactions between doxycycline / salicylic acid topical and mycophenolic acid

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

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Interactions between your drugs

Major

doxycycline mycophenolic acid

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

Drug and food/lifestyle interactions

Moderate

mycophenolic acid food/lifestyle

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

doxycycline food/lifestyle

Applies to: doxycycline / salicylic acid topical

GENERALLY AVOID: The oral bioavailability of quinolone and tetracycline antibiotics may be reduced by concurrent administration of preparations containing polyvalent cations such as aluminum, calcium, iron, magnesium, and zinc. Therapeutic failure may result. The proposed mechanism is chelation of quinolone and tetracycline antibiotics by di- and trivalent cations, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. Reduced gastrointestinal absorption of the cations should also be considered.

MANAGEMENT: Concomitant administration of oral quinolone and tetracycline antibiotics with preparations containing aluminum, calcium, iron, magnesium, and/or zinc salts should generally be avoided. Otherwise, the times of administration should be staggered by as much as possible to minimize the potential for interaction. Quinolones should typically be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation preparations, depending on the quinolone and formulation. Likewise, tetracyclines and polyvalent cation preparations should typically be administered 2 to 4 hours apart. The prescribing information for the antibiotic should be consulted for more specific dosing recommendations.

References (51)
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  2. Nix DE, Watson WA, Lener ME, et al. (1989) "Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin." Clin Pharmacol Ther, 46, p. 700-5
  3. Garrelts JC, Godley PJ, Peterie JD, Gerlach EH, Yakshe CC (1990) "Sucralfate significantly reduces ciprofloxacin concentrations in serum." Antimicrob Agents Chemother, 34, p. 931-3
  4. Frost RW, Lasseter KC, Noe AJ, Shamblen EC, Lettieri JT (1992) "Effects of aluminum hydroxide and calcium carbonate antacids on the bioavailability of ciprofloxacin." Antimicrob Agents Chemother, 36, p. 830-2
  5. Yuk JH (1989) "Ciprofloxacin levels when receiving sucralfate." J Am Geriatr Soc, 262, p. 901
  6. Neuvonen PJ (1976) "Interactions with the absorption of tetracyclines." Drugs, 11, p. 45-54
  7. Deppermann KM, Lode H, Hoffken G, Tschink G, Kalz C, Koeppe P (1989) "Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid." Antimicrob Agents Chemother, 33, p. 1901-7
  8. Nguyen VX, Nix DE, Gillikin S, Schentag JJ (1989) "Effect of oral antacid administration on the pharmacokinetics of intravenous doxycycline." Antimicrob Agents Chemother, 33, p. 434-6
  9. Campbell NR, Kara M, Hasinoff BB, Haddara WM, McKay DW (1992) "Norfloxacin interaction with antacids and minerals." Br J Clin Pharmacol, 33, p. 115-6
  10. Parpia SH, Nix DE, Hejmanowski LG, Goldstein HR, Wilton JH, Schentag JJ (1989) "Sucralfate reduces the gastrointestinal absorption of norfloxacin." Antimicrob Agents Chemother, 33, p. 99-102
  11. Nix DE, Wilton JH, Ronald B, Distlerath L, Williams VC, Norman A (1990) "Inhibition of norfloxacin absorption by antacids." Antimicrob Agents Chemother, 34, p. 432-5
  12. Akerele JO, Okhamafe AO (1991) "Influence of oral co-administered metallic drugs on ofloxacin pharmacokinetics." J Antimicrob Chemother, 28, p. 87-94
  13. Gothoni G, Neuvonen PJ, Mattila M, Hackman R (1972) "Iron-tetracycline interaction: effect of time interval between the drugs." Acta Med Scand, 191, p. 409-11
  14. Garty M, Hurwitz A (1980) "Effect of cimetidine and antacids on gastrointestinal absorption of tetracycline." Clin Pharmacol Ther, 28, p. 203-7
  15. Gotz VP, Ryerson GG (1986) "Evaluation of tetracycline on theophylline disposition in patients with chronic obstructive airways disease." Drug Intell Clin Pharm, 20, p. 694-6
  16. McCormack JP, Reid SE, Lawson LM (1990) "Theophylline toxicity induced by tetracycline." Clin Pharm, 9, p. 546-9
  17. D'Arcy PF, McElnay JC (1987) "Drug-antacid interactions: assessment of clinical importance." Drug Intell Clin Pharm, 21, p. 607-17
  18. Wadworth AN, Goa KL (1991) "Lomefloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use." Drugs, 42, p. 1018-60
  19. Shimada J, Shiba K, Oguma T, et al. (1992) "Effect of antacid on absorption of the quinolone lomefloxacin." Antimicrob Agents Chemother, 36, p. 1219-24
  20. Upton RA (1991) "Pharmacokinetic interactions between theophylline and other medication (Part I)." Clin Pharmacokinet, 20, p. 66-80
  21. Venho VM, Salonen RO, Mattila MJ (1978) "Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal." Eur J Clin Pharmacol, 14, p. 277-80
  22. (2002) "Product Information. Minocin (minocycline)." Lederle Laboratories
  23. Sahai J, Healy DP, Stotka J, Polk RE (1993) "The influence of chronic administration of calcium carbonate on the bioavailability of oral ciprofloxacin." Br J Clin Pharmacol, 35, p. 302-4
  24. (2001) "Product Information. Declomycin (demeclocycline)." Lederle Laboratories
  25. Lehto P, Kivisto KT (1994) "Effect of sucralfate on absorption of norfloxacin and ofloxacin." Antimicrob Agents Chemother, 38, p. 248-51
  26. Noyes M, Polk RE (1988) "Norfloxacin and absorption of magnesium-aluminum." Ann Intern Med, 109, p. 168-9
  27. Grasela TH Jr, Schentag JJ, Sedman AJ, et al. (1989) "Inhibition of enoxacin absorption by antacids or ranitidine." Antimicrob Agents Chemother, 33, p. 615-7
  28. Campbell NR, Hasinoff BB (1991) "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol, 31, p. 251-5
  29. Covington TR, eds., Lawson LC, Young LL (1993) "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association
  30. Lehto P, Kivisto KT (1994) "Different effects of products containing metal ions on the absorption of lomefloxacin." Clin Pharmacol Ther, 56, p. 477-82
  31. Bateman FJ (1970) "Effects of tetracyclines." Br Med J, 4, p. 802
  32. Neuvonen PJ, Gothoni G, Hackman R, Bjorksten K (1970) "Interference of iron with the absorption of tetracyclines in man." Br Med J, 4, p. 532-4
  33. Greenberger NJ (1971) "Absorption of tetracyclines: interference by iron." Ann Intern Med, 74, p. 792-3
  34. Neuvonen PJ, Penttila O (1974) "Effect of oral ferrous sulphate on the half-life of doxycycline in man." Eur J Clin Pharmacol, 7, p. 361-3
  35. Spivey JM, Cummings DM, Pierson NR (1996) "Failure of prostatitis treatment secondary to probable ciprofloxacin-sucralfate drug interaction." Pharmacotherapy, 16, p. 314-6
  36. (2001) "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical
  37. (2001) "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome
  38. (2001) "Product Information. Zagam (sparfloxacin)." Rhone Poulenc Rorer
  39. (2001) "Product Information. Trovan (trovafloxacin)." Pfizer U.S. Pharmaceuticals
  40. Teng R, Dogolo LC, Willavize SA, Friedman HL, Vincent J (1997) "Effect of Maalox and omeprazole on the bioavailability of trovafloxacin." J Antimicrob Chemother, 39 Suppl B, p. 93-7
  41. Zix JA, Geerdes-Fenge HF, Rau M, Vockler J, Borner K, Koeppe P, Lode H (1997) "Pharmacokinetics of sparfloxacin and interaction with cisapride and sucralfate." Antimicrob Agents Chemother, 41, p. 1668-72
  42. Honig PK, Gillespie BK (1998) "Clinical significance of pharmacokinetic drug interactions with over-the-counter (OTC) drugs." Clin Pharmacokinet, 35, p. 167-71
  43. Johnson RD, Dorr MB, Talbot GH, Caille G (1998) "Effect of Maalox on the oral absorption of sparfloxacin." Clin Ther, 20, p. 1149-58
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  45. Allen A, Vousden M, Porter A, Lewis A (1999) "Effect of Maalox((R)) on the bioavailability of oral gemifloxacin in healthy volunteers." Chemotherapy, 45, p. 504-11
  46. Kamberi M, Nakashima H, Ogawa K, Oda N, Nakano S (2000) "The effect of staggered dosing of sucralfate on oral bioavailability of sparfloxacin." Br J Clin Pharmacol, 49, p. 98-103
  47. (2003) "Product Information. Factive (gemifloxacin)." *GeneSoft Inc
  48. (2010) "Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates)." Braintree Laboratories
  49. (2017) "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc.
  50. (2018) "Product Information. Seysara (sarecycline)." Allergan Inc
  51. (2018) "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc.
Minor

doxycycline food/lifestyle

Applies to: doxycycline / salicylic acid topical

Chronic alcohol consumption may enhance the elimination of doxycycline. The mechanism is induction of hepatic microsomal enzymes by alcohol. In one study, the half-life of doxycycline in six alcoholics was 10.5 hours, compared with 14.7 hours in six control patients. In addition, half the alcoholic patients had serum concentrations below what is generally considered the minimum therapeutic concentration (0.5 mcg/mL) at 12 to 24 hours after the dose. The investigators suggest that twice-a-day dosing may be indicated in these patients, especially if additional inducing drugs are used. The elimination of other tetracyclines probably is not affected by alcohol consumption.

References (1)
  1. Neuvonen PJ, Penttila O, Roos M, Tirkkonen J (1976) "Effect of long-term alcohol consumption on the half-life of tetracycline and doxycycline in man." Int J Clin Pharmacol Biopharm, 14, p. 303-7

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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