Nutrition Support Consultant - SAGE Journals

Hospital Pharmacy Volume 39, Number 1, pp 84–89, 96 2004 Wolters Kluwer Health, Inc.

Nutrition Support Consultant Medication Administration Considerations for Patients Receiving Enteral Tube Feedings Roland N. Dickerson, PharmD, BCNSP, CNS, FACN, FCCP*

Nutrition Support Consultant features issues pertinent to the clinical aspects of pharmacy nutrition support practice. The column is edited by Dr. Roland Dickerson, Professor of Pharmacy, University of Tennessee Health Science Center, Memphis, TN. Address correspondence to Roland N. Dickerson, PharmD, University of Tennessee Health Science Center, 26 Dunlap St., Memphis, TN 38163.

B

oth pharmacotherapy and metabolic support therapy have become exceedingly complex for critically ill patients. As a result, the use of medications for patients receiving specialized nutrition support can be problematic, particularly when oral medications are given to patients receiving continuous enteral feeding.1–5 The intent of this brief overview is to summarize the major issues surrounding drug administration in tube-fed patients, share some of my clinical experiences, and provide practical suggestions for circumventing potential complications. Patients who require enteral feedings are often administered medications through their feeding tubes for the convenience of the patient and nursing staff. In some cases, medications must be administered via feeding tube if the patient aspirates when swallowing or by jejunostomy tube if he or she cannot be fed into the stomach.

*Professor of Pharmacy, University of Tennessee Health Science Center; Memphis, TN.

84

Volume 39, January 2004

Parenteral administration of medications might appear to be somewhat simpler; however, it is more costly and involves complications associated with IV access. Medications administered by feeding tube are often given as suspensions, liquids, or elixirs. However, many medications are not available in ready-to-administer liquid forms. Tablets are crushed to a fine powder, mixed to a slurry in water, and administered via the feeding tube. The tube is flushed with water before and after the medication is given. Capsules are opened and the contents are administered in the same manner. This method of drug administration may clog feeding tubes, especially if done inappropriately; however, for some patients, there are no other options. SORBITOL CONTENT AND HYPEROSMOLALITY OF ORAL DRUG SOLUTIONS Many liquid and elixir medication formulations contain sorbitol,6–9 which can cause osmotic diarrhea. Some of the first case reports about the diarrhea-inducing sorbitol content of liquid med-

ications described this problem with theophylline liquid.8,9 Acetaminophen liquid is another common preparation that can cause diarrhea in hospitalized patients, because as much as 8 to 24 g of sorbitol daily can be ingested with conventional acetaminophen therapy used to reduce fever.6 When acetominophen liquid is prescribed by the primary service, we alter the dosage form to tablets, then prepare and administer them in the manner described above to avoid this common potential complication. Lutomski and Miller evaluated the sorbitol content of various liquid and elixir medication formulations.2,7 It is also important to consider the amount of medication liquid given per dose. The pharmacist can then determine whether the sorbitol dosage is sufficient to induce adverse gastrointestinal (GI) events. The usual minimum laxative dose for sorbitol is approximately 20 grams; however, some patients may be sensitive to smaller doses.7 Some of the most common sorbitol-containing liquid medications are listed in Table 1. Sorbitol contents are not necessarily specific to the medication and may reflect the industry’s formulation practices. For example, potassium chloride liquid may or may not contain sorbitol depending on the manufacturer.6 Although publications may list sorbitol-containing liquids, the sorbitol content of each preparation is subject to

Nutrition Support Consultant

Table 1. Medication Formulations With Substantial Sorbitol Intake at Conventional Doses* Acetaminophen liquid Amantidine liquid Cimetidine liquid Guaifenesin/dextromethorphan syrup Isoniazid liquid Lithium citrate liquid Metoclopramide syrup Phenylephrine/brompheniramine elixir Phenylephrine/chlorpheniramine elixir Potassium chloride liquid Potassium gluconate elixir Pseudoephedrine/tripolidine syrup Theophylline oral solution/elixir *Depending on the manufacturer, some formulations of these products may not have substantial sorbitol contents Adapted from Gora et al2 and Miller & Oliver7

change, because manufacturers may alter the “inert” ingredients of their liquid formulations. Therefore, there are many uncertainties about the sorbitol content of a specific formulation without recent verification from the manufacturer. At my institution, we experienced the rare situation whereby a manufacturer’s representative refused to provide the exact amount of sorbitol in a liquid formulation, because “it was an inert substance and amounts of these inert ingredients are considered proprietary information necessary for development of the formulation.” As a result, we changed the patient’s pharmacotherapy to exclude this formulation and reassessed the patient’s GI tolerance. The hyperosmolality of certain

medication solutions may also be a cause of GI intolerance.10–13 It has been recommended that electrolyte supplementation by parenteral means or by appropriate dilution and mixture with an enteral formula is preferable to bolus administration of undiluted solutions via the feeding tube. However, there are caveats to this recommendation. It has been well established that hypertonic tube feedings and medications can often be tolerated without adverse complications when given intragastrically.14–16 This would appear intuitive, as one of the functions of the stomach is to act as a reservoir and dilute hypertonic substances with gastric secretions as it prepares nutrients to be transferred to the small bowel. However, dysregulation of this function may occur in those individuals with “dumping syndrome” or rapid gastric transit times. Bolus administration of large amounts of hypertonic medications directly into the small bowel (eg, jejunostomy) should be avoided because they may result in intestinal intolerance, including cramping, bloating, and diarrhea. The total osmotic load of the medication in question should be evaluated before administration, particularly for patients who are fed directly into the small bowel. For example, saturated solution of potassium iodide may be alarmingly hypertonic at approximately 11,000 mOsm/Kg;10 however, this medication formulation is dosed in such small volume units that it can easily be diluted to tolerable osmotic loads when administered concomitantly with water flushes. Alternatively, a medication solution such as 10% potassium chloride liquid has an osmolality of about 3000 to 3500 mOsm/kg10 and is given in fairly large volume

units (eg, 30 mL). Administration of bolus doses of 10% potassium chloride into the small bowel by a nasoduodenal tube has been previously reported to induce diarrhea.12 In a case from my practice, the multidisciplinary nutrition support team was consulted for a patient who had “malabsorption” of tube feeds with significant volumes of 4 to 6 liquid stools per day. The patient was also noted to have systemic candidiasis and was being treated with amphotericin B therapy. Due to the amphotericin B therapy, the patient had significant hypokalemia and was being aggressively treated with multiple 40 mEq KCL liquid boluses via the feeding tube (surprisingly, hypomagnesemia was not evident). In addition to its osmolality, KCL is inherently “irritating” to the vein or GI tract. Almost like clockwork, the patient experienced a large loose stool 1 to 2 hours after each administration of potassium chloride solution. Rather than switching to an elemental diet or provide parenteral nutrition, we added 80 mEq of potassium chloride to each liter of the isotonic, polymeric, fiber-containing enteral feeding solution and stopped the intermittent KCL boluses via the feeding tube. The patient received nearly 2 L/day of enteral feeding solution. Any additional potassium requirements were then given intravenously by a large-volume parenteral solution. The patient’s diarrhea resolved to about two bowel movements per day after these changes. Although this case may be the exceptional “perfect example” rather than the norm encountered in clinical practice, it illustrates how patients receiving specialized nutrition support need to be monitored for medication-induced GI

Hospital Pharmacy

85


distress. The osmolality of various common medication solutions are listed in Table 2. Interestingly, many of the hypertonic medications also contain substantial amounts of sorbitol (see Tables 1 and 2). Our article concerning the osmolality of various medication solutions was published nearly a decade sooner than the reports about the high sorbitol content of some of these preparations. Taken together, these data may indicate that GI intolerance to some hypertonic medications may potentially be related to high sorbitol content. One analytical method that may help ascertain whether diarrhea is being induced osmotically by a medication solution is to measure and calculate the stool osmotic gap. This process involves obtaining a liquid stool sample and sending it to the clinical laboratory for sodium (Na) concentration, potassium (K) concentration, and osmolality. The stool osmotic gap can be estimated by the following equation: Osmotic Gap = Measured stool osmolality – 2 x [stool Na (mEq/L) + stool K (mEq/L)]

If the gap is greater than 150 to 200, it is very likely that the patient has an osmotic diarrhea due to medications. Some investigators consider an osmotic gap as low as greater than 100 as reflective of osmotic diarrhea.9 (Unfortunately, many hospital laboratories are incapable of measuring stool osmolality.) Before undergoing an extensive work-up, the clinician should make sure that the patient is not taking any laxatives or any medications that might cause diarrhea. I have experienced numerous situations whereby the patient had “intolerance of tube feeding,” as described by the primary service,

86


only to find that patient had been receiving lactulose, oral magnesium sulfate, erythromycin, laxatives, broad-spectrum antibiotics, or other pharmacotherapies that commonly cause diarrhea. Any hospitalized, enterally fed patient experiencing diarrhea that has received antibiotics should be closely evaluated for alteration of bacterial flora of the intestinal tract, including the presence of Clostridium difficile toxin. Patients with diarrhea and a history of recent ingestion of raw shellfish should also have their stool evaluated for ova and parasites. ADMINISTRATION OF SUSTAINEDRELEASE MEDICATIONS Provision of enteric-coated or micro-encapsulated medication formulations to tube-fed patients provides an additional challenge. Some clinicians have suggested that the pellets inside the microencapsulated medication formulation be directly poured down the feeding tube.5 The feeding tube is then flushed well with water. Enteric coatings generally do not crush well and tend to aggregate when moistened, often leading to tube clogging.5 Like enteric-coated and microencapsulated medications, sustained-release products should not be crushed. As long as the tube feeding does not interfere with the absorption of the medication, sustained-release products may be used for patients receiving enteral feedings if the patient can swallow and has an intact GI tract. If this is not the case, the sustained-release medication may have to be provided in smaller, more frequent doses per the tube or alternative pharmacotherapy may need to be considered. We recently reported the case of a drug misadventure whereby

Table 2. Medication Formulations Resulting in Significant Osmotic Load at Conventional Dose Acetaminophen liquid Amantidine liquid Chloral hydrate syrup Cimetidine solution Dextromethorphan syrup Docusate syrup Lithium citrate syrup Metoclopramide syrup Potassium chloride liquid, 10% Sodium phosphate liquid Adapted from Dickerson & Melnik10

the sustained-release product was erroneously converted to a single large dose of the immediate-release product.17 The medication was crushed and administered to the patient with significant adverse effects.17 A comprehensive list of medications that should not be crushed has been compiled;18 however, new sustained-release products are constantly emerging. A unique drug administration consideration is the delivery of the sustained-release proton pump inhibitors omeprazole and lansoprazole. Both formulations contain delayed-release, base-labile granules for an acid-labile medication. For administration via a gastric feeding tube, acidic liquids may need to be coadministered with the medication to prevent acid degradation in the stomach prior to reaching the small intestine for absorption. Alkaline liquids may be given when the drugs are administered by jejunostomy.5,19 The clinical relevance of this practice has been questioned.20 As a result, some institutions have implemented a standardized suspension of omeprazole or lansoprazole in sodium bicarbonate


Table 3. Guidelines for Medication Administration for Patients Receiving Enteral Tube Feeding 1. Oral administration is preferred whenever possible. 2. Flush the feeding tube with water prior to and after medication administration. 3. The drug should be diluted with water when administered into the small bowel if the medication solution is extremely hypertonic. 4. If the medication contains a substantial amount of sorbitol or is enteric-coated, an alternative dosage form should be considered. 5. Immediate-release tablets should be crushed to a fine powder and mixed with water to form a slurry mixture prior to administration via the feeding tube. 6. For an immediate-release capsule, open the capsule and mix the contents with water to form a slurry mixture. 7. Aspirate the contents of soft-gelatin immediate-release capsules using a needle and syringe, then mix with water prior to administration. However, because of the viscosity, an alternative dosage form or medication should be considered. 8. The pharmacotherapy regimen of a sustained-release tablet should be changed to a therapeutically equivalent short-acting preparation with lower doses, with multiple doses given per day, or consider an alternative pharmacotherapy. 9. For a sustained-release capsule with intact pellets, consider opening the capsule and pouring the contents down the feeding tube, the flush well with water — or consider an alternative pharmacotherapy. 10.When using phenytoin, warfarin, or any other therapy whereby the absorption of the medication is significantly impaired in the presence of continuous enteral feeding, the feeding should be held for at least 1 to 2 hours prior to and after the dose. Adapted from Dickerson et al17

injection, given irrespectively of gastric or small bowel administration.21–23 This practice is not universal among leading hospitals and should be considered somewhat controversial until more data are available. COMPATIBILITY OF ENTERAL FEEDINGS WITH DRUG SOLUTIONS Many liquid drug formulations are physically incompatible with enteral feeding,24–27 which can lead to tube clogging. Of particular note are those medications provided in a syrup dosage form. Their propensity for causing tube clogging is likely due to the viscosity of the medication carrier solution.

Ferrous sulfate liquid, when inadvertently mixed with enteral feeding solutions, has commonly clogged feeding tubes in hospitalized and long-term care patients. Because of these drug administration problems, most patient care protocols require that the medications be given separately from enteral feeding as a bolus. The medication is usually preceded by a water flush to clear the feeding tube of enteral solution and then followed by a water flush to clear the drug prior to reinitiating enteral feeding. Sevelamer, a relatively new medication used to manage hyperphosphatemia during renal failure,

has been inadvertently given by feeding tube. This waxy-like polymer has consistently clogged patients’ feeding tubes when accidentally given via small-bore feeding tubes at our institution. An alternative medication, such as calcium acetate, should be used in lieu of sevelamer when medications are administered via a feeding tube. Another consideration in the delivery of medications by feeding tube and tube clogging is the bore size (gauge) of the feeding tube. Currently, we administer medication via conventional feeding tubes greater than 8 Fr gauge in size (most institutions use 8, 10, or 12 Fr gauge as their conventional nasoenteric feeding tube size for adults). We have been reluctant to use extremely small bore feeding tubes such as a needle catheter jejunostomy for administration of medications due to the potential increased risk of clogging and the inability of replacement of the clogged tube. Fortunately, with regard to drug administration considerations, needle catheter jejunostomies are rarely used in contemporary clinical practice. COMPATIBILITY OF DRUG SOLUTIONS WITH ENTERAL FEEDINGS The bioavailability of some medications may be altered by enteral feeding. The most commonly described problems in hospitalized patients occur with the quinolones (ciprofloxacin, ofloxacin, levofloxacin),28–30 phenytoin,11,31–36 and warfarin.37–39 The quinolones, when administered with metallic cations such as calcium, aluminum, magnesium and iron, have resulted in reduced bioavailability. Although the concentration of these minerals are substantially

Hospital Pharmacy

87


lower in commercial enteral feeding solutions than in mineral supplements or antacids, decreased bioavailability has been noted when quinolones have been coadministered with enteral feeding.28–30 Despite reduced absorption when administered with enteral feeding, ciprofloxacin serum concentrations were still well above the minimum inhibitory concentrations for many pathogenic bacteria in one study.40 These data have led to controversy regarding the clinical relevance of this interaction. It is recommended that the quinolones not be administered via a jejunostomy tube — irrespective of enteral feeding — as it appears that the duodenum is the major site for its absorption.28 The reader is referred to a comprehensive review regarding the use of ciprofloxacin in the enterally-fed patient.41 Phenytoin and enteral feeding is likely the best known interaction of all the known drug–enteral feeding interactions.11,31–36 Numerous reviews have been written on this subject, including a previous review in the Nutrition Support Consultant series for this journal.42 The etiology for this decreased bioavailability is not entirely clear; however, it may be related to binding of phenytoin to calcium caseinates or protein hydrolysates in the enteral feedings. Despite numerous case reports, case series, and in-vitro and in-vivo studies, there is a small faction of practitioners who do not believe that this interaction exists.43 This controversy stems from two studies showing no effect of feeding on phenytoin absorption in normal volunteers receiving bolus enteral feeding.44,45 I have observed this phenomenon in practice and have discussed this issue with numerous nutrition support pharmacy spe-

88


cialists with considerable experience with large volumes of critically ill patients that have also had similar experiences. I agree with Hatton and Magnusson’s summary of this potential interaction: “We strongly disagree that this effect is a ‘myth’ and believe that the risk of ignoring this potential contributing factor to subtherapeutic phenytoin levels is too great for clinical practitioners to disregard enteral nutrition effects until definitive patient trials are performed.”46 Although Bauer’s original report32 suggested withholding feeding for 2 hours before and after phenytoin administration, the effect of this intervention was not studied. One uncontrolled study suggested that clamping the gastrostomy feeding tube for 1 hour after the phenytoin dosage resulted in higher serum phenytoin concentrations in head-injured patients;31 however, this intervention clearly requires more study. It is our current practice to withhold enteral feeding for at least 1 hour prior to and after the administration of phenytoin. Enteral nutrition has long been established as a cause of warfarin resistance.47–49 More than two decades ago, this resistance was attributed to the vitamin K content of the enteral feeding solution. Manufacturers have reformulated the enteral feeding products to contain substantially less vitamin K. But despite these reformulations, there still appears to be an interaction between warfarin and commercial enteral feeding products. In-vitro investigations of this interaction revealed that warfarin binds to the enteral feeding, resulting in reduced bioavailability.37,39 The exact mechanism for this binding is unclear, but may be related to warfarin’s natural propensity

for protein binding. Warfarin likely binds to the soy proteins or proteinaceous caseinate salts in the feedings.37,39 The importance of this interaction needs to be further elucidated; however, two published reports describing three patient cases provide limited evidence of its clinical significance.37,38 Our empiric approach to the problem has been to withhold feeding for 1 hour before and 1 hour after administration of warfarin. We have had success in achieving adequate anticoagulation with reasonable warfarin dosing with this approach; however, this technique requires scientific study. Clinicians have empirically held tube feedings for 1 to 2 hours before and after the administration of medications with documented decreased bioavailability when given along with enteral feeding.31,32 Unfortunately, the efficacy of this practice in improving drug absorption has not been adequately studied. In addition, these discontinuations of enteral feeding will necessitate a higher infusion rate in order to receive the same amount of daily feeding, since the duration of daily feeding is shortened from its continuous infusion over 24 hours. This increased rate of tube feeding infusion may adversely influence GI tolerance for some individuals. CONCLUSIONS There are numerous issues related to safe and effective delivery of medications to enterally-fed patients. Because of these difficulties in drug administration of various dosage forms, guidelines for safe drug administration have been compiled from various sources1,2,4,5,17 and are summarized in Table 3. These guidelines are not all-inclusive; however, they, togeth-


er with the recommendations made in this review, should address many of the drug administration situations encountered in acutecare clinical practice. As more data become available, the guidelines in Table 3 and various issues discussed throughout this article are likely to change. There may be exceptions to the guidelines, as various alternative methods may be preferred in selected cases. For drugs with a narrow therapeutic index, changes in the patient’s pharmacotherapy need to be reevaluated with clinical monitoring for evidence of therapeutic efficacy or adverse effects including determination of serum concentrations of the medication if necessary. Readers are strongly encouraged to examine the excellent reviews by Gora et al2 and Beckwith et al5 prior to developing guidelines for medication administration for patients receiving specialized enteral nutrition support at your institution. REFERENCES 1. Estoup M. Approaches and limitations of medication delivery in patients with enteral feeding tubes. Crit Care Nurse. 1994;14:68–72,77–9. 2. Gora ML, Tschampel MM, Visconti JA. Considerations of drug therapy in patients receiving enteral nutrition. Nutr Clin Pract. 1989;4:105–10. 3. Smith CH, Bidlack WR. Dietary concerns associated with the use of medications. J Am Diet Assoc. 1984;84:901–14. 4. Engle KK, Hannawa TE. Techniques for administering oral medications to critical care patients receiving continuous enteral nutrition. Am J Health Syst Pharm. 1999;56:1441–4. 5. Beckwith MC, Barton RG, Graves C. A guide to drug therapy in patients with enteral feeding tubes: Dosage form selection and administration methods. Hosp Pharm. 1997;32:57–64. 6. Lutomski DM, Gora ML, Wright SM, et al. Sorbitol content of selected oral liquids. Ann Pharmacother. 1993;27:269–74.

7. Miller SJ, Oliver AD. Sorbitol content of selected sugar-free liquid medications. Hosp Pharm. 1993;28:741–4. 8. Hill DB, Henderson LM, McClain CJ. Osmotic diarrhea induced by sugarfree theophylline solution in critically ill patients. JPEN J Parenter Enteral Nutr. 1991;15:332–6. 9. Edes TE, Walk BE, Austin JL. Diarrhea in tube-fed patients: Feeding formula not necessarily the cause. Am J Med. 1990;88:91–3. 10.Dickerson RN, Melnik G. Osmolality of oral drug solutions and suspensions. Am J Hosp Pharm. 1988;45:832–4. 11.Holtz L, Milton J, Sturek JK. Compatibility of medications with enteral feedings. JPEN J Parenter Enteral Nutr. 1987;11:183–6. 12.Niemiec PW, Jr., Vanderveen TW, Morrison JI, et al. Gastrointestinal disorders caused by medication and electrolyte solution osmolality during enteral nutrition. JPEN J Parenter Enteral Nutr. 1983;7:387–9. 13.White KC, Harkavy KL. Hypertonic formula resulting from added oral medications. Am J Dis Child. 1982;136:931–3. 14.Keohane PP, Attrill H, Love M, et al. Relation between osmolality of diet and gastrointestinal side effects in enteral nutrition. BMJ (Clin Res Ed). 1984; 288:678–80. 15.Pesola GR, Hogg JE, Eissa N, et al. Hypertonic nasogastric tube feedings: Do they cause diarrhea? Crit Care Med. 1990;18:1378–82. 16.Guenter PA, Settle RG, Perlmutter S, et al. Tube feeding-related diarrhea in acutely Ill patients. JPEN J Parenter Enteral Nutr. 1991;15:277–80. 17.Dickerson RN, Tidwell AC, Brown RO. Adverse effects from inappropriate medication administration via a jejunostomy feeding tube. Nutr Clin Pract. 2003;18:402–8. 18.Mitchell JE. Oral dosage forms that should not be crushed: 1998 update. Hosp Pharm. 1998;33:399–415. 19.Chun AH, Shi HH, Achari R, et al. Lansoprazole: Administration of the contents of a capsule dosage formulation through a nasogastric tube. Clin Ther. 1996;18:833–42. 20.Phillips JO, Olsen KM, Rebuck JA, et al. A randomized, pharmacokinetic and pharmacodynamic, cross-over study of

duodenal or jejunal administration compared to nasogastric administration of omeprazole suspension in patients at risk for stress ulcers. Am J Gastroenterol. 2001;96:367–72. 21.McAndrews KL, Jr., Eastham JH. Omeprazole and lansoprazole suspensions for nasogastric administration. Am J Health Syst Pharm. 1999;56:81. 22.Dunn A, White CM, Reddy P, et al. Delivery of omeprazole and lansoprazole granules through a nasogastric tube in vitro. Am J Health Syst Pharm. 1999;56:2327-30. 23.Quercia RA, Fan C, Liu X, et al. Stability of omeprazole in an extemporaneously prepared oral liquid. Am J Health Syst Pharm. 1997;54:1833–6. 24.Cutie AJ, Altman E, Lenkel L. Compatibility of enteral products with commonly employed drug additives. JPEN J Parenter Enteral Nutr. 1983;7:186–91. 25.Burns PE, McCall L, Wirsching R. Physical compatibility of enteral formulas with various common medications. J Am Diet Assoc. 1988;88:1094–6. 26.Altman E, Cutie AJ. Compatibility of enteral products with commonly employed drug additives. Nutr Supp Serv. 1984;4:8–17. 27.Fagerman KE, Ballou AE. Drug compatibilities with enteral feeding solutions coadministered by tube. Nutr Supp Serv. 1988;8:31–2. 28.Healy DP, Brodbeck MC, Clendening CE. Ciprofloxacin absorption is impaired in patients given enteral feedings orally and via gastrostomy and jejunostomy tubes. Antimicrob Agents Chemother. 1996;40:6–10. 29.Mueller BA, Brierton DG, Abel SR, et al. Effect of enteral feeding with ensure on oral bioavailabilities of ofloxacin and ciprofloxacin. Antimicrob Agents Chemother. 1994;38:2101–5. 30.Mimoz O, Binter V, Jacolot A, 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;24:1047–51. 31.Faraji B, Yu PP. Serum phenytoin levels of patients on gastrostomy tube feeding. J Neurosci Nurs. 1998;30:55–9. 32.Bauer LA. Interference of oral phenytoin absorption by continuous nasogastric feedings. Neurology. 1982;32:570–2. 33.Maynard GA, Jones KM, Guidry JR.

Hospital Pharmacy

89


Phenytoin absorption from tube feedings. Arch Intern Med. 1987;147:1821. 34.Sneed RC, Morgan WT. Interference of oral phenytoin absorption by enteral tube feedings. Arch Phys Med Rehabil. 1988;69:682–4. 35.Hooks MA, Longe RL, Taylor AT, et al. Recovery of phenytoin from an enteral nutrient formula. Am J Hosp Pharm. 1986;43:685–8. 36.Cacek AT, DeVito JM, Koonce JR. In vitro evaluation of nasogastric administration methods for phenytoin. Am J Hosp Pharm. 1986;43:689–92. 37.Penrod LE, Allen JB, Cabacungan LR. Warfarin resistance and enteral feedings: Two case reports and a supporting in vitro study. Arch Phys Med Rehabil. 2001;82:1270–3. 38.Petretich DA. Reversal of Osmolitewarfarin interaction by changing warfarin administration time. Clin Pharm.

90


1990;9:93. 39.Kuhn TA, Garnett WR, Wells BK, et al. Recovery of warfarin from an enteral nutrient formula. Am J Hosp Pharm. 1989;46:1395–9. 40.Cohn SM, Sawyer MD, Burns GA, et al. Enteric absorption of ciprofloxacin during tube feeding in the critically ill. J Antimicrob Chemother. 1996;38:871–6. 41.Nyffeler MS. Ciprofloxacin use in the enterally fed patient. Nutr Clin Pract. 1999;14:73–7. 42.Pugh CB. Phenytoin and enteral feedings: A clinically significant interaction. Hosp Pharm. 1989;24:562–9. 43.Bertino JS, Naderer O. Is the phenytoin-enteral feeding formula interaction a myth? [letter]. Nutr Clin Pract. 1996;11:175–6. 44.Marvel ME, Bertino JS, Jr. Comparative effects of an elemental and a complex enteral feeding formulation on the

absorption of phenytoin suspension. JPEN J Parenter Enteral Nutr. 1991;15:316–8. 45.Krueger KA, Garnett WR, Comstock TJ, et al. Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability. Epilepsia. 1987;28:706–12. 46.Hatton J, Magnusson B. Response to Drs. Bertino and Naderer [letter]. Nutr Clin Pract. 1996;11:176. 47.Lee M, Schwartz RN, Sharifi R. Warfarin resistance and vitamin K. Ann Intern Med. 1981;94:140–1. 48.Zallman JA, Lee DP, Jeffrey PL. Liquid nutrition as a cause of warfarin resistance. Am J Hosp Pharm. 1981;38:1174. 49.Parr MD, Record KE, Griffith GL, et al. Effect of enteral nutrition on warfarin therapy. Clin Pharm. 1982;1:274–6. ■