Skip to main content

Drug Interactions between Cipro I.V. and simvastatin

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

ciprofloxacin simvastatin

Applies to: Cipro I.V. (ciprofloxacin) and simvastatin

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of HMG-CoA reductase inhibitors (i.e., statins) that are metabolized by the isoenzyme. Lovastatin and simvastatin are particularly susceptible because of their low oral bioavailability, but others such as atorvastatin and cerivastatin may also be affected. 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. Clinically significant interactions have been reported with potent CYP450 3A4 inhibitors such as macrolide antibiotics, azole antifungals, protease inhibitors and nefazodone, and moderate inhibitors such as amiodarone, cyclosporine, danazol, diltiazem and verapamil.

MANAGEMENT: Caution is recommended if atorvastatin, cerivastatin, lovastatin, simvastatin, or red yeast rice (which contains lovastatin) is prescribed with a CYP450 3A4 inhibitor. It is advisable to monitor lipid levels and use the lowest effective statin dose. 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. Fluvastatin, pravastatin, and rosuvastatin are not expected to interact with CYP450 3A4 inhibitors.

References

  1. Spach DH, Bauwens JE, Clark CD, Burke WG (1991) "Rhabdomyolysis associated with lovastatin and erythromycin use." West J Med, 154, p. 213-5
  2. Ayanian JZ, Fuchs CS, Stone RM (1988) "Lovastatin and rhabdomyolysis." Ann Intern Med, 109, p. 682-3
  3. Corpier CL, Jones PH, Suki WN, et al. (1988) "Rhabdomyolysis and renal injury with lovastatin use. Report of two cases in cardiac transplant recipients." JAMA, 260, p. 239-41
  4. East C, Alivizatos PA, Grundy SM, Jones PH, Farmer JA (1988) "Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation." N Engl J Med, 318, p. 47-8
  5. Norman DJ, Illingworth DR, Munson J, Hosenpud J (1988) "Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin." N Engl J Med, 318, p. 46-7
  6. (2002) "Product Information. Mevacor (lovastatin)." Merck & Co., Inc
  7. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  8. Dallaire M, Chamberland M (1994) "Severe rhabdomyolysis in a patient receiving lovastatin, danazol and doxycycline." Can Med Assoc J, 150, p. 1991-4
  9. Campana C, Iacona I, Regassi MB, et al. (1995) "Efficacy and pharmacokinetics of simvastatin in heart transplant recipients." Ann Pharmacother, 29, p. 235-9
  10. Lees RS, Lees AM (1995) "Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole." N Engl J Med, 333, p. 664-5
  11. Zhou LX, Finley DK, Hassell AE, Holtzman JL (1995) "Pharmacokinetic interaction between isradipine and lovastatin in normal, female and male volunteers." J Pharmacol Exp Ther, 273, p. 121-7
  12. Neuvonen PJ, Jalava KM (1996) "Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 60, p. 54-61
  13. Horn M (1996) "Coadministration of itraconazole with hypolipidemic agents may induce rhabdomyolysis in healthy individuals." Arch Dermatol, 132, p. 1254
  14. (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
  15. Jacobson RH, Wang P, Glueck CJ (1997) "Myositis and rhabdomyolysis associated with concurrent use of simvastatin and nefazodone." JAMA, 277, p. 296
  16. Jody DN (1997) "Myositis and rhabdomyolysis associated with concurrent use of simvastatin and nefazodone." JAMA, 277, p. 296-7
  17. (2001) "Product Information. Baycol (cerivastatin)." Bayer
  18. Grunden JW, Fisher KA (1997) "Lovastatin-induced rhabdomyolysis possibly associated with clarithromycin and azithromycin." Ann Pharmacother, 31, p. 859-63
  19. Wong PW, Dillard TA, Kroenke K (1998) "Multiple organ toxicity from addition of erythromycin to long-term lovastatin therapy." South Med J, 91, p. 202-5
  20. Neuvonen PJ, Kantola T, Kivisto KT (1998) "Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole." Clin Pharmacol Ther, 63, p. 332-41
  21. Agbin NE, Brater DC, Hall SD (1997) "Interaction of diltiazem with lovastatin and pravastatin." Clin Pharmacol Ther, 61, p. 201
  22. Kivisto KT, Kantola T, Neuvonen PJ (1998) "Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin." Br J Clin Pharmacol, 46, p. 49-53
  23. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Effect of itraconazole on the pharmacokinetics of atorvastatin." Clin Pharmacol Ther, 64, p. 58-65
  24. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations." Clin Pharmacol Ther, 64, p. 177-82
  25. Azie NE, Brater DC, Becker PA, Jones DR, Hall SD (1998) "The interaction of diltiazem with lovastatin and pravastatin." Clin Pharmacol Ther, 64, p. 369-77
  26. Lomaestro BM, Piatek MA (1998) "Update on drug interactions with azole antifungal agents." Ann Pharmacother, 32, p. 915-28
  27. Kantola T, Kivisto KT, Neuvonen PJ (1999) "Effect of itraconazole on cerivastatin pharmacokinetics." Eur J Clin Pharmacol, 54, p. 851-5
  28. Malaty LI, Kuper JJ (1999) "Drug interactions of HIV protease inhibitors." Drug Safety, 20, p. 147-69
  29. Siedlik PH, Olson SC, Yang BB, Stern RH (1999) "Erythromycin coadministration increases plasma atorvastatin concentrations." J Clin Pharmacol, 39, p. 501-4
  30. Barry M, Mulcahy F, Merry C, Gibbons S, Back D (1999) "Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection." Clin Pharmacokinet, 36, p. 289-304
  31. Rodriguez JA, CrespoLeiro MG, Paniagua MJ, Cuenca JJ, Hermida LF, Juffe A, CastroBeiras A (1999) "Rhabdomyolysis in heart transplant patients on HMG-CoA reductase inhibitors and cyclosporine." Transplant Proc, 31, p. 2522-3
  32. Gruer PJK, Vega JM, Mercuri MF, Dobrinska MR, Tobert JA (1999) "Concomitant use of cytochrome P450 3A4 inhibitors and simvastatin." Am J Cardiol, 84, p. 811-5
  33. Gilad R, Lampl Y (1999) "Rhabdomyolysis induced by simvastatin and ketoconazole treatment." Clin Neuropharmacol, 22, p. 295-7
  34. Gullestad L, Nordal KP, Berg KJ, Cheng H, Schwartz MS, Simonsen S (1999) "Interaction between lovastatin and cyclosporine A after heart and kidney transplantation." Transplant Proc, 31, p. 2163-5
  35. Yeo KR, Yeo WW, Wallis EJ, Ramsay LE (1999) "Enhanced cholesterol reduction by simvastatin in diltiazem-treated patients." Br J Clin Pharmacol, 48, p. 610-5
  36. Maltz HC, Balog DL, Cheigh JS (1999) "Rhabdomyolysis associated with concomitant use of atorvastatin and cyclosporine." Ann Pharmacother, 33, p. 1176-9
  37. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  38. Jardine A, Holdaas H (1999) "Fluvastatin in combination with cyclosporin in renal transplant recipients: a review of clinical and safety experience." J Clin Pharm Ther, 24, p. 397-408
  39. Mousa O, Brater DC, Sundblad KJ, Hall SD (2000) "The interaction of diltiazem with simvastatin." Clin Pharmacol Ther, 67, p. 267-74
  40. Westphal JF (2000) "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, p. 285-95
  41. Kusus M, Stapleton DD, Lertora JJL, Simon EE, Dreisbach AW (2000) "Rhabdomyolysis and acute renal failure in a cardiac transplant recipient due to multiple drug interactions." Am J Med Sci, 320, p. 394-7
  42. Lee AJ, Maddix DS (2001) "Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin." Ann Pharmacother, 35, p. 26-31
  43. Yeo KR, Yeo WW (2001) "Inhibitory effects of verapamil and diltiazem on simvastatin metabolism in human liver microsomes." Br J Clin Pharmacol, 51, p. 461-70
  44. Arnadottir M, Eriksson LO, Thysell H, Karkas JD (1993) "Plasma concentration profiles of simvastatin 3-hydroxy- 3-methylglutaryl-coenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin." Nephron, 65, p. 410-3
  45. Corsini A, Bellosta S, Baetta R, Fumagalli R, Paoletti R, Bernini F (1999) "New insights into the pharmacodynamic and pharmacokinetic properties of statins." Pharmacol Ther, 84, p. 413-28
  46. Garnett WR (1995) "Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors." Am J Health Syst Pharm, 52, p. 1639-45
  47. Omar MA, Wilson JP (2002) "FDA adverse event reports on statin-associated rhabdomyolysis." Ann Pharmacother, 36, p. 288-95
  48. Fichtenbaum CJ, Gerber JG, Rosenkranz SL, et al. (2002) "Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047." AIDS, 16, p. 569-577
  49. Amsden GW, Kuye O, Wei GC (2002) "A study of the interaction potential of azithromycin and clarithromycin with atorvastatin in healthy volunteers." J Clin Pharmacol, 42, p. 444-9
  50. Williams D, Feely J (2002) "Pharmacokinetic-Pharmacodynamic Drug Interactions with HMG-CoA Reductase Inhibitors." Clin Pharmacokinet, 41, p. 343-70
  51. Thompson M, Samuels S (2002) "Rhabdomyolysis with simvastatin and nefazodone." Am J Psychiatry, 159, p. 1607
  52. Huynh T, Cordato D, Yang F, et al. (2002) "HMG coA reductase-inhibitor-related myopathy and the influence of drug interactions." Intern Med J, 32(9-10), p. 486-90
  53. Paoletti R, Corsini A, Bellosta S (2002) "Pharmacological interactions of statins." Atheroscler Suppl, 3, p. 35-40
  54. Sipe BE, Jones RJ, Bokhart GH (2003) "Rhabdomyolysis Causing AV Blockade Due to Possible Atorvastatin, Esomeprazole, and Clarithromycin Interaction." Ann Pharmacother, 37, p. 808-11
  55. de Denus S, Spinler SA (2003) "Amiodarone's role in simvastatin-associated rhabdomyolysis." Am J Health Syst Pharm, 60, 1791; author reply 1791-2
  56. Skrabal MZ, Stading JA, Monaghan MS (2003) "Rhabdomyolysis associated with simvastatin-nefazodone therapy." South Med J, 96, p. 1034-5
  57. Andreou ER, Ledger S (2003) "Potential drug interaction between simvastatin and danazol causing rhabdomyolysis." Can J Clin Pharmacol, 10, p. 172-4
  58. Roten L, Schoenenberger RA, Krahenbuhl S, Schlienger RG (2004) "Rhabdomyolysis in association with simvastatin and amiodarone." Ann Pharmacother, 38, p. 978-81
  59. Jacobson TA (2004) "Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors." Am J Cardiol, 94, p. 1140-6
  60. Chouhan UM, Chakrabarti S, Millward LJ (2005) "Simvastatin interaction with clarithromycin and amiodarone causing myositis." Ann Pharmacother, 39, p. 1760-1
  61. Karnik NS, Maldonado JR (2005) "Antidepressant and statin interactions: a review and case report of simvastatin and nefazodone-induced rhabdomyolysis and transaminitis." Psychosomatics, 46, p. 565-8
  62. Neuvonen PJ, Backman JT, Niemi M (2008) "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet, 47, p. 463-74
  63. (2021) "Product Information. Qelbree (viloxazine)." Supernus Pharmaceuticals Inc
View all 63 references

Switch to consumer interaction data

Drug and food interactions

Major

simvastatin food

Applies to: simvastatin

GENERALLY AVOID: Coadministration with grapefruit juice may significantly increase the plasma concentrations of lovastatin and simvastatin and their active acid metabolites. 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 60 mg dose of simvastatin was coadministered with 200 mL of double-strength grapefruit juice three times a day, simvastatin systemic exposure (AUC) increased by 16-fold and simvastatin acid AUC increased by 7-fold. Administration of a single 20 mg dose of simvastatin with 8 ounces of single-strength grapefruit juice increased the AUC of simvastatin and simvastatin acid by 1.9-fold and 1.3-fold, respectively. The interaction has also been reported with lovastatin, which has a similar metabolic profile to simvastatin. 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.

Coadministration with green tea may increase the plasma concentrations of simvastatin. The mechanism of interaction has not been established, but may involve inhibition of organic anion transporting polypeptide (OATP) 1B1- and/or 2B1-mediated hepatic uptake of simvastatin by catechins in green tea. The interaction was suspected in a 61-year-old man who experienced muscle intolerance during treatment with simvastatin while drinking an average of 3 cups of green tea daily. He also experienced similar muscle intolerance (leg cramps without creatine phosphokinase elevation) during treatments with atorvastatin and rosuvastatin while drinking green tea. Pharmacokinetic studies performed during his usual green tea intake demonstrated an approximately two-fold higher exposure to simvastatin lactone (the administered form of simvastatin) than that observed after stopping green tea intake for a month. He was also able to tolerate simvastatin after discontinuing green tea consumption. The authors of the report subsequently conducted two independent studies to assess the effect of different green tea preparations on simvastatin pharmacokinetics. One study was conducted in 12 Italian subjects and the other in 12 Japanese subjects. In the Italian study, administration of a single 20 mg dose of simvastatin following pretreatment with 200 mL of a hot green tea standardized infusion 3 times daily for 14 days (estimated daily intake of 335 mg total catechins and 173 mg epigallocatechin-3-gallate (EGCG), the most abundant and biologically active catechin in green tea) was found to have no significant effect on mean peak plasma concentration (Cmax) or systemic exposure (AUC) of simvastatin lactone and simvastatin acid relative to administration with water. However, green tea increased simvastatin lactone AUC (0-6h) by about two-fold in 3 of the study subjects. In the Japanese study, administration of a single 10 mg dose of simvastatin following pretreatment with 350 mL of a commercial green tea beverage twice daily for 14 days (estimated daily intake of 638 mg total catechins and 322 mg EGCG) did not affect mean simvastatin lactone Cmax or AUC to a statistically significant extent compared to administration with water, but increased mean simvastatin acid Cmax and AUC by 42% and 22%, respectively. Similar to the first study, green tea increased simvastatin lactone AUC (0-6h) by two- to three-fold in 4 of the study subjects. Although not studied, the interaction may also occur with lovastatin due to its similar metabolic profile to simvastatin.

MANAGEMENT: Patients receiving therapy with lovastatin, simvastatin, or red yeast rice (which contains lovastatin) should be advised to avoid the consumption of grapefruit and grapefruit juice. Fluvastatin, pravastatin, pitavastatin, and rosuvastatin are metabolized by other enzymes and may be preferable alternatives in some individuals. 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. Also, patients should either refrain from the use of oat bran and pectin, or separate the administration times by at least 2 to 4 hours if concurrent use cannot be avoided. Caution may be advisable when coadministered with green tea or green tea extracts. Dosing reduction of the statin and/or limiting consumption of green tea and green tea products may be required if an interaction is suspected.

References

  1. Richter WO, Jacob BG, Schwandt P (1991) "Interaction between fibre and lovastatin." Lancet, 338, p. 706
  2. (2002) "Product Information. Mevacor (lovastatin)." Merck & Co., Inc
  3. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  4. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
  5. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  6. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  7. Thompson PD, Clarkson P, Karas RH (2003) "Statin-associated myopathy." JAMA, 289, p. 1681-90
  8. Neuvonen PJ, Backman JT, Niemi M (2008) "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet, 47, p. 463-74
  9. Werba JP, Giroli M, Cavalca V, Nava MC, Tremoli E, Dal Bo L (2008) "The effect of green tea on simvastatin tolerability." Ann Intern Med, 149, p. 286-7
  10. Werba JP, Misaka S, Giroli MG, et al. (2014) "Overview of Green Tea Interaction with Cardiovascular Drugs." Curr Pharm Des
  11. Roth M, Timmermann BN, Hagenbuch B (2011) "Interactions of green tea catechins with organic anion-transporting polypeptides." Drug Metab Dispos, 39, p. 920-6
  12. Knop J, Misaka S, Singer K, et al. (2015) "Inhibitory effects of green tea and (-)-epigallocatechin gallate on transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-glycoprotein." PLoS One, 10, e0139370
View all 12 references

Switch to consumer interaction data

Moderate

ciprofloxacin food

Applies to: Cipro I.V. (ciprofloxacin)

ADJUST DOSING INTERVAL: Concurrent ingestion of dairy products (milk, yogurt) or calcium-fortified foods (i.e., cereal, orange juice) may decrease the activity of certain oral fluoroquinolone antibiotics. The mechanism is chelation of calcium and the quinolone, resulting in decreased bioavailability. In the case of orange juice, inhibition of intestinal transport mechanisms (P-glycoprotein or organic anion-transporting polypeptides) by flavones may also be involved. One study reported an average 41% decrease in maximum plasma concentrations and a 38% decrease in AUC when ciprofloxacin was given with calcium-fortified orange juice instead of water. Administration of ciprofloxacin tablets with enteral nutrition may reduce its bioavailability and maximum serum concentrations. Data have been conflicting and variable by the type of enteral nutrition product, location of the feeding tube, and patient characteristics. Decreased absorption is expected if ciprofloxacin is given by jejunostomy tube.

MANAGEMENT: Oral ciprofloxacin should not be taken with dairy products or calcium-fortified foods alone, but may be taken with meals that contain these products. When taken alone, dairy products or calcium-fortified foods should be ingested at least 2 hours before or after ciprofloxacin administration. When ciprofloxacin tablets are administered to patients receiving continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 2 hours after the dose of ciprofloxacin is given. Patients should be monitored for altered antimicrobial efficacy and switched to intravenous ciprofloxacin if necessary. If no enteral route besides a jejunostomy tube is available, it is also recommended to switch to intravenous ciprofloxacin. According to the manufacturer, ciprofloxacin oral suspension should not be administered via nasogastric or feeding tubes due to its physical characteristics.

References

  1. (2002) "Product Information. Cipro (ciprofloxacin)." Bayer
  2. Yuk JH, Nightingale CH, Sweeney KR, Quintiliani R, Lettieri JT, Forst RW (1989) "Relative bioavailability in healthy volunteers of ciprofloxacin administered through a nasogastric tube with and without enteral feeding." Antimicrob Agents Chemother, 33, p. 1118-20
  3. Yuk JH, Nightingale CH, Quintiliani R (1990) "Absorption of ciprofloxacin administered through a nasogastric or a nasoduodenal tube in volunteers and patients receiving enteral nutrition." Diagn Microbiol Infect Dis, 13, p. 99-102
  4. Noer BL, Angaran DW (1990) "The effect of enteral feedings on ciprofloxacin pharmacokinetics." Pharmacotherapy, 10, p. 254
  5. Neuhofel AL, Wilton JH, Victory JM, Hejmanowsk LG, Amsden GW (2002) "Lack of bioequivalence of ciprofloxacin when administered with calcium-fortified orange juice: a new twist on an old interaction." J Clin Pharmacol, 42, p. 461-6
  6. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67
View all 6 references

Switch to consumer interaction data

Moderate

simvastatin food

Applies to: simvastatin

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.

References

  1. (2001) "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb
  2. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  3. (2001) "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals
  4. (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
  5. (2002) "Product Information. Altocor (lovastatin)." Andrx Pharmaceuticals
  6. (2003) "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  8. Cerner Multum, Inc. "Australian Product Information."
  9. (2010) "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic)
View all 9 references

Switch to consumer interaction data

Moderate

ciprofloxacin food

Applies to: Cipro I.V. (ciprofloxacin)

ADJUST DOSING INTERVAL: Oral preparations that contain magnesium, aluminum, or calcium may significantly decrease the gastrointestinal absorption of quinolone antibiotics. 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 quinolones by polyvalent cations, forming a complex that is poorly absorbed from the gastrointestinal tract. The bioavailability of ciprofloxacin has been reported to decrease by as much as 90% when administered with antacids containing aluminum or magnesium hydroxide.

MANAGEMENT: When coadministration cannot be avoided, quinolone antibiotics should be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation-containing products to minimize the potential for interaction. When coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering fluoroquinolone antibiotics at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium. Please consult individual product labeling for specific recommendations.

References

  1. Polk RE, Helay DP, Sahai J, Drwal L, Racht E (1989) "Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers." Antimicrob Agents Chemother, 33, p. 1841-4
  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. 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
  7. 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
  8. 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
  9. 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
  10. Akerele JO, Okhamafe AO (1991) "Influence of oral co-administered metallic drugs on ofloxacin pharmacokinetics." J Antimicrob Chemother, 28, p. 87-94
  11. Wadworth AN, Goa KL (1991) "Lomefloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use." Drugs, 42, p. 1018-60
  12. 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
  13. 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
  14. Lehto P, Kivisto KT (1994) "Effect of sucralfate on absorption of norfloxacin and ofloxacin." Antimicrob Agents Chemother, 38, p. 248-51
  15. Noyes M, Polk RE (1988) "Norfloxacin and absorption of magnesium-aluminum." Ann Intern Med, 109, p. 168-9
  16. 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
  17. Lehto P, Kivisto KT (1994) "Different effects of products containing metal ions on the absorption of lomefloxacin." Clin Pharmacol Ther, 56, p. 477-82
  18. Spivey JM, Cummings DM, Pierson NR (1996) "Failure of prostatitis treatment secondary to probable ciprofloxacin-sucralfate drug interaction." Pharmacotherapy, 16, p. 314-6
  19. (2001) "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical
  20. (2001) "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome
  21. (2001) "Product Information. Zagam (sparfloxacin)." Rhone Poulenc Rorer
  22. (2001) "Product Information. Trovan (trovafloxacin)." Pfizer U.S. Pharmaceuticals
  23. 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
  24. 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
  25. Honig PK, Gillespie BK (1998) "Clinical significance of pharmacokinetic drug interactions with over-the-counter (OTC) drugs." Clin Pharmacokinet, 35, p. 167-71
  26. Johnson RD, Dorr MB, Talbot GH, Caille G (1998) "Effect of Maalox on the oral absorption of sparfloxacin." Clin Ther, 20, p. 1149-58
  27. Lober S, Ziege S, Rau M, Schreiber G, Mignot A, Koeppe P, Lode H (1999) "Pharmacokinetics of gatifloxacin and interaction with an antacid containing aluminum and magnesium." Antimicrob Agents Chemother, 43, p. 1067-71
  28. 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
  29. 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
  30. (2003) "Product Information. Factive (gemifloxacin)." *GeneSoft Inc
  31. (2010) "Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates)." Braintree Laboratories
  32. (2017) "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc.
View all 32 references

Switch to consumer interaction data

Moderate

ciprofloxacin food

Applies to: Cipro I.V. (ciprofloxacin)

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

Switch to consumer interaction data

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.

See also

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer