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Drug Interactions between Baycol and Eryzole

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

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Interactions between your drugs

Major

erythromycin cerivastatin

Applies to: Eryzole (erythromycin / sulfisoxazole) and Baycol (cerivastatin)

ADJUST DOSE: Some macrolide antibiotics inhibit CYP450 3A4 and may elevate the plasma concentrations of HMG-CoA reductase inhibitors that are metabolized by the isoenzyme. Macrolides that may significantly inhibit CYP450 3A4 include troleandomycin, erythromycin, and clarithromycin. There have been case reports of patients treated with lovastatin or simvastatin who developed severe myopathy or rhabdomyolysis following the addition of a macrolide, usually erythromycin. Plasma levels of HMG-CoA reductase inhibitory activity were significantly elevated in these patients, up to severalfold in many cases. Similar pharmacokinetic changes have been reported in studies with erythromycin and simvastatin and, to a lesser extent, with clarithromycin or erythromycin and atorvastatin. The interaction was also suspected in a patient treated with atorvastatin (more than 1 year) and esomeprazole (6 weeks) who developed rhabdomyolysis with AV block two days after the addition of clarithromycin. The patient reported experiencing symptoms of increased fatigue, mild chest pain, and shortness of breath that coincided with the initiation of esomeprazole approximately six weeks prior to admission.

MANAGEMENT: The benefits of using HMG-CoA reductase inhibitors that are metabolized by CYP450 3A4 in combination with medications that can inhibit the isoenzyme such as clarithromycin and erythromycin should be carefully weighed against the potentially increased risk of myopathy including rhabdomyolysis. A lower dosage of the HMG-CoA reductase inhibitor should be considered if concomitant use is required. Atorvastatin labeling recommends that the dosage not exceed 20 mg/day when used in combination with clarithromycin. Fluvastatin, pitavastatin, and rosuvastatin may be safer alternatives, since they are not metabolized by CYP450 3A4. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

References

  1. Spach DH, Bauwens JE, Clark CD, Burke WG "Rhabdomyolysis associated with lovastatin and erythromycin use." West J Med 154 (1991): 213-5
  2. Ayanian JZ, Fuchs CS, Stone RM "Lovastatin and rhabdomyolysis." Ann Intern Med 109 (1988): 682-3
  3. Corpier CL, Jones PH, Suki WN, et al. "Rhabdomyolysis and renal injury with lovastatin use. Report of two cases in cardiac transplant recipients." JAMA 260 (1988): 239-41
  4. East C, Alivizatos PA, Grundy SM, Jones PH, Farmer JA "Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation." N Engl J Med 318 (1988): 47-8
  5. "Product Information. Mevacor (lovastatin)." Merck & Co., Inc PROD (2002):
  6. "Product Information. Zocor (simvastatin)." Merck & Co., Inc PROD (2001):
  7. "Product Information. Lipitor (atorvastatin)." Parke-Davis PROD (2001):
  8. "Product Information. Baycol (cerivastatin)." Bayer PROD (2001):
  9. Grunden JW, Fisher KA "Lovastatin-induced rhabdomyolysis possibly associated with clarithromycin and azithromycin." Ann Pharmacother 31 (1997): 859-63
  10. Wong PW, Dillard TA, Kroenke K "Multiple organ toxicity from addition of erythromycin to long-term lovastatin therapy." South Med J 91 (1998): 202-5
  11. Kantola T, Kivisto KT, Neuvonen PJ "Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations." Clin Pharmacol Ther 64 (1998): 177-82
  12. Siedlik PH, Olson SC, Yang BB, Stern RH "Erythromycin coadministration increases plasma atorvastatin concentrations." J Clin Pharmacol 39 (1999): 501-4
  13. Westphal JF "Macrolide - induced clinically relevant drug interactions with cytochrome P-450 (CYP) 3A4: an update focused on clarithromycin, azithromycin, and dirithromycin." Br J Clin Pharmacol 50 (2000): 285-95
  14. Lee AJ, Maddix DS "Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin." Ann Pharmacother 35 (2001): 26-31
  15. Garnett WR "Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors." Am J Health Syst Pharm 52 (1995): 1639-45
  16. Omar MA, Wilson JP "FDA adverse event reports on statin-associated rhabdomyolysis." Ann Pharmacother 36 (2002): 288-95
  17. Amsden GW, Kuye O, Wei GC "A study of the interaction potential of azithromycin and clarithromycin with atorvastatin in healthy volunteers." J Clin Pharmacol 42 (2002): 444-9
  18. Williams D, Feely J "Pharmacokinetic-Pharmacodynamic Drug Interactions with HMG-CoA Reductase Inhibitors." Clin Pharmacokinet 41 (2002): 343-70
  19. Huynh T, Cordato D, Yang F, et al. "HMG coA reductase-inhibitor-related myopathy and the influence of drug interactions." Intern Med J 32(9-10) (2002): 486-90
  20. Sipe BE, Jones RJ, Bokhart GH "Rhabdomyolysis Causing AV Blockade Due to Possible Atorvastatin, Esomeprazole, and Clarithromycin Interaction." Ann Pharmacother 37 (2003): 808-11
  21. Chouhan UM, Chakrabarti S, Millward LJ "Simvastatin interaction with clarithromycin and amiodarone causing myositis." Ann Pharmacother 39 (2005): 1760-1
  22. Neuvonen PJ, Backman JT, Niemi M "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet 47 (2008): 463-74
  23. Cooper JM, Jones AL "Neuroleptic malignant syndrome or a statin drug reaction? A case report." Clin Neuropharmacol 32 (2009): 348-9
View all 23 references

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Drug and food interactions

Moderate

erythromycin food

Applies to: Eryzole (erythromycin / sulfisoxazole)

ADJUST DOSING INTERVAL: Food may variably affect the bioavailability of different oral formulations and salt forms of erythromycin. The individual product package labeling should be consulted regarding the appropriate time of administration in relation to food ingestion. Grapefruit juice may increase the plasma concentrations of orally administered erythromycin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In an open-label, crossover study consisting of six healthy subjects, the coadministration with double-strength grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single dose of erythromycin (400 mg) by 52% and 49%, respectively, compared to water. The half-life was not affected. The clinical significance of this potential interaction is unknown.

MANAGEMENT: In general, optimal serum levels are achieved when erythromycin is taken in the fasting state, one-half to two hours before meals. However, some erythromycin products may be taken without regard to meals.

References

  1. Welling PG, Huang H, Hewitt PF, Lyons LL "Bioavailability of erythromycin stearate: influence of food and fluid volume." J Pharm Sci 67 (1978): 764-6
  2. Welling PG, Elliott RL, Pitterle ME, et al. "Plasma levels following single and repeated doses of erythromycin estolate and erythromycin stearate." J Pharm Sci 68 (1979): 150-5
  3. Welling PG "Influence of food and diet on gastrointestinal drug absorption: a review." J Pharmacokinet Biopharm 5 (1977): 291-334
  4. Coyne TC, Shum S, Chun AH, Jeansonne L, Shirkey HC "Bioavailability of erythromycin ethylsuccinate in pediatric patients." J Clin Pharmacol 18 (1978): 194-202
  5. Malmborg AS "Effect of food on absorption of erythromycin. A study of two derivatives, the stearate and the base." J Antimicrob Chemother 5 (1979): 591-9
  6. Randinitis EJ, Sedman AJ, Welling PG, Kinkel AW "Effect of a high-fat meal on the bioavailability of a polymer-coated erythromycin particle tablet formulation." J Clin Pharmacol 29 (1989): 79-84
  7. Kanazawa S, Ohkubo T, Sugawara K "The effects of grapefruit juice on the pharmacokinetics of erythromycin." Eur J Clin Pharmacol 56 (2001): 799-803
View all 7 references

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Moderate

cerivastatin food

Applies to: Baycol (cerivastatin)

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of atorvastatin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. When a single 40 mg dose of atorvastatin was coadministered with 240 mL of grapefruit juice, atorvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 16% and 37%, respectively. Greater increases in Cmax (up to 71%) and/or AUC (up to 2.5 fold) have been reported with excessive consumption of grapefruit juice (>=750 mL to 1.2 liters per day). Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

ADJUST DOSING INTERVAL: Fibres such as oat bran and pectin may diminish the pharmacologic effects of HMG-CoA reductase inhibitors by interfering with their absorption from the gastrointestinal tract.

MANAGEMENT: Patients receiving therapy with atorvastatin should limit their consumption of grapefruit juice to no more than 1 liter per day. Patients should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. In addition, patients should either refrain from the use of oat bran and pectin or, if concurrent use cannot be avoided, to separate the administration times by at least 2 to 4 hours.

References

  1. Richter WO, Jacob BG, Schwandt P "Interaction between fibre and lovastatin." Lancet 338 (1991): 706
  2. McMillan K "Considerations in the formulary selection of hydroxymethylglutaryl coenzyme a reductase inhibitors." Am J Health Syst Pharm 53 (1996): 2206-14
  3. "Product Information. Lipitor (atorvastatin)." Parke-Davis PROD (2001):
  4. Boberg M, Angerbauer R, Fey P, Kanhai WK, Karl W, Kern A, Ploschke J, Radtke M "Metabolism of cerivastatin by human liver microsomes in vitro. Characterization of primary metabolic pathways and of cytochrome P45 isozymes involved." Drug Metab Dispos 25 (1997): 321-31
  5. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  6. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther 66 (1999): 118-27
  7. Neuvonen PJ, Backman JT, Niemi M "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet 47 (2008): 463-74
View all 7 references

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Minor

erythromycin food

Applies to: Eryzole (erythromycin / sulfisoxazole)

Ethanol, when combined with erythromycin, may delay absorption and therefore the clinical effects of the antibiotic. The mechanism appears to be due to slowed gastric emptying by ethanol. Data is available only for erythromycin ethylsuccinate. Patients should be advised to avoid ethanol while taking erythromycin salts.

References

  1. Morasso MI, Chavez J, Gai MN, Arancibia A "Influence of alcohol consumption on erythromycin ethylsuccinate kinetics." Int J Clin Pharmacol 28 (1990): 426-9

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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

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