Nov 27, 2012
Ciprofloxacin binds to divalent and trivalent cations (calcium, magnesium, etc). Are there any recommendations regarding giving crushed ciprofloxacin via an enteral feeding tube, such as holding nutrition or increasing the dose?
The package insert for ciprofloxacin tablets states that the medication may be given with or without food. If given with food, the peak onset will be delayed by one hour (1 hr vs. 2 hrs), but overall absorption is not affected. If ciprofloxacin is given with divalent/trivalent cation-containing substances (calcium, magnesium, zinc, iron, aluminium) that are common in antacids and multivitamins, bioavailability can be reduced as much as 90%.
Because enteral nutrition often contains these cations, which can reduce bioavailability, there is controversy regarding whether enteral nutrition should be held in patients receiving crushed ciprofloxacin via a feeding tube.
Evidence: Water vs. Enteral Nutrition
- In a single-dose, crossover trial of 6 healthy volunteers comparing water to Osmolite, there was no significant difference in AUC, Cmax, or time to peak. Although not significant, numerically, AUC was reduced by 24% and Cmax by 27% with Osmolite.1
- In a single-dose, crossover trial of 13 healthy volunteers comparing water to Ensure, those receiving Ensure had a significant decrease in AUC (27% reduction, p<0.0005), Cmax (47% reduction, p<0.005), and bioavailability (28% less, p<0.005).2
- In a single-dose, crossover trial of 10 G-tube and 6 J-tube patients comparing water versus Jevity, those receiving Jevity had a significant decrease in AUC (53-67% reduction) and Cmax (38-62% reduction) (p<0.05).3
Evidence: Bioavailability with Enteral Nutrition
- According to the package insert, ciprofloxacin should have a bioavailability of about 70%. For this reason, the package insert suggests an IV:PO conversion of 400 mg IV = 500 mg PO.
- A multiple dose crossover trial of 5 ICU patients receiving continuous enteral nutrition compared ciprofloxacin 750 mg PO BID versus 400 mg IV BID. The study concluded that the oral bioavailability was approximately 50%, indicating a rough equivalence of 750 mg PO and 400 mg IV.4
- A multiple dose crossover trial of 12 mechanically ventilated patients with continuous enteral nutrition compared ciprofloxacin 750 mg PO BID versus 400 mg IV BID. The study concluded that the oral bioavailability was 44%, although the range was quite wide (31-82%).5
- There is a significant interaction between enteral feeds and crushed ciprofloxacin
- Compared to water alone, enteral feeds will reduce AUC by 24 to 67% and Cmax by 27 to 62%
- The IV:PO conversion of patients receiving enteral nutrition is not the standard 400:500 mg (based on 70% bioavailability)
- As with other antibiotics in critically ill patients, given the erratic bioavailability of oral ciprofloxacin, IV ciprofloxacin should be continued until the patient is hemodynamically stable with a functional GI tract and has demonstrated clinical improvement.
- In theory, holding tube feeds 2 hours before and 4 hours after fluoroquinolone administration should avoid the drug-food interaction. While this recommendation is made in at least one review article,6 it would only allow for 12 hours of feeding in patients receiving Q12hr ciprofloxacin.
- A more practical approach may be to increase the ciprofloxacin dose to account for a decreased bioavailability. Two studies of 17 patients indicate a bioavailability of approximately 50%, although the range is quite variable. Based on these studies, an appropriate dose conversion is 400 mg IV = 750 mg per NG/OG tube.
- Importantly, using a higher dose may have safety concerns in patients who are able to consume a normal diet (no need for tube feeding) or those in which enteral nutrition is held. Ideally, one should have a mechanism in place to adjust the dose once the patient's condition changes.
- Yuk et al. Relative bioavailability in healthy volunteers of ciprofloxacin administered through a nasogastric tube with and without enteral feeding. Antimicrob Agents Chemother. 1989;33(7):1118-20. PMID 2506806.
- Mueller et al. Effect of enteral feeding with ensure on oral bioavailabilities of ofloxacin and ciprofloxacin. Antimicrob Agents Chemother. 1994;38(9):2101-5. PMID 7811026.
- Healy et al. Ciprofloxacin absorption is impaired in patients given enteral feedings orally and via gastrostomy and jejunostomy tubes. Antimicrob Agents Chemother. 1996;40(1):6-10. PMID 8787869.
- de Marie et al. Bioavailability of ciprofloxacin after multiple enteral and intravenous doses in ICU patients with severe gram-negative intra-abdominal infections. Intensive Care Med. 1998;24(4):343-6. PMID 9609412.
- Mimoz et al. Pharmacokinetics and absolute bioavailability of ciprofloxacin administered through a nasogastric tube with continuous enteral feeding to critically ill patients. Intensive Care Med. 1998;24(10):1047-51. PMID 9840238.
- Beckwith et al. A Guide to Drug Therapy in Patients with Enteral Feeding Tubes: Dosage Form Selection and Administration Methods. Hosp Pharm. 2004;39:225-237. PDF online.